<\/span><\/h1>\n<\/span><\/h1>\n<\/span><\/h1>\nThe Engle Lab<\/span><\/h1>\nat the F.M. Kirby Neurobiology Center<\/span><\/h2>\n<\/span><\/h1>\n<\/span><\/h1>\n<\/h1>\n<\/span><\/strong><\/h2>\n[\/et_pb_text][et_pb_text _builder_version=”4.5.0″ width=”163%” max_width=”100%” custom_margin=”|-989px||||” custom_padding=”7px|40px||103px|false|false”]<\/p>\n
<\/span><\/p>\nPatient & Study Participant Resources<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.5.3″ custom_padding=”0|0px|47.625px|0|false|false”][et_pb_row _builder_version=”4.5.0″ _module_preset=”default” custom_padding=”||0px|||”][et_pb_column type=”4_4″ _builder_version=”4.5.0″ _module_preset=”default”][et_pb_text _builder_version=”4.5.3″ _module_preset=”default”]<\/p>\n
Welcome, we are glad you found us!\u00a0<\/strong><\/h2>\nYou may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information will address questions you may have about enrolling in our research and\/or attending our CCDD Consultation Clinic.<\/p>\n
From a research standpoint, the Engle Lab strives to better understand the neurogenetic basis of cranial nerve development and function.\u00a0 This is done through gene discovery and basic research described in the Science section<\/a> of our website. Gene discovery requires the enrollment and participation of individuals and families diagnosed with rare conditions involving atypical or limited eye and facial movements. These conditions include both defined or undefined congenital cranial dysinnervation disorders (CCDDs)<\/a>\u00a0and familial strabismus<\/a>.<\/p>\nDr. Engle and her colleagues also oversee and participate in a multi-disciplinary, second-opinion consultation clinic at Boston Children\u2019s Hospital for children and adults diagnosed with ocular CCDDs. This clinic is staffed by two physicians, Dr. Elizabeth Engle, a child neurologist and pediatrician, and Dr. David Hunter, an ophthalmologist, as well as an\u00a0orthoptist <\/a>and genetic counselor<\/a>.\u00a0More information on this clinic is provided in\u00a0\u00a0“Attending the Ocular CCDD Clinic”<\/a>.<\/p>\n\n- See our FAQs section<\/a> for definitions and additional background.<\/li>\n<\/ul>\n
How can I participate or become involved?<\/h2>\n
There is overlap between the conditions studied by the Engle Lab and the conditions seen through the CCDD clinic at Boston Children\u2019s Hospital.\u00a0 However, the research and formal medical evaluations are performed through separate programs. People can choose to participate in, and be appropriate for, one or both options.\u00a0 To pre-screen individuals for either program (research enrollment or clinic visit), Dr. Engle and her team review clinical information provided through forms and medical records. This helps us to be sure that the desired study and\/or clinic participation are appropriate.<\/p>\n
Continue reading below to learn more or click on the buttons to move to a specific section.<\/p>\n
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<\/p>\n<\/p>\nEnrolling Into Our Research<\/div>\n <\/div>\n
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[\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsCCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
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<\/p>\n<\/p>\nAttending Ocular CCDD Clinic<\/div>\n <\/div>\n
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<\/p>\n<\/p>\nFrequently Asked Questions (FAQs)<\/div>\n <\/div>\n
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Dr. Elizabeth Engle (center, front) and members of the Engle Lab commemorating Moebius Syndrome Awareness Day 2020.<\/em><\/p>\n[\/et_pb_text][et_pb_text module_id=”genetics” _builder_version=”4.5.3″ max_width=”100%” custom_margin=”|-571px||||”]<\/p>\n
Enrolling in Engle Lab Research Studies<\/h2>\n
The Engle Lab\u2019s research enrollment goals are to (1) enroll participants who are born with complex eye and facial movement disorders or disorders of lower cranial nerve function together with family members and\u00a0 (2) enroll families in which three or more relatives are diagnosed with strabismus.\u00a0 Patients, parents, health care providers and other researchers all refer individuals to us for enrollment.<\/p>\n
Examples of disorders we study:<\/h3>\n\n- Complex congenital eye and eyelid movement disorders:<\/li>\n
\n- Congenital Fibrosis of the Extraocular Muscles (CFEOM)<\/li>\n
- Congenital ptosis<\/li>\n
- Marcus Gunn Jaw Winking syndrome (MGJWS)<\/li>\n
- Duane syndrome \/ Duane retraction syndrome (DRS)<\/li>\n
- Horizontal Gaze Palsy (HGP)<\/li>\n
- Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)<\/li>\n
- Moebius syndrome \/ Moebius sequence (MBS)<\/li>\n
- Congenital 3rd, 4th, or 6th nerve palsy<\/li>\n
- Ocular and lid synkinesis<\/li>\n
- Any other complex congenital eye or lid movement disorder (yet to be defined)<\/li>\n<\/ul>\n
- Congenital facial weakness or palsy<\/li>\n
\n- Isolated congenital facial weakness<\/li>\n
- Syndromic congenital facial weakness<\/li>\n
- Moebius syndrome<\/li>\n<\/ul>\n
- Congenital disorders of lower cranial nerves<\/li>\n
\n- Examples include disorders of tongue movement, chewing, or swallowing<\/li>\n<\/ul>\n
- Familial Strabismus<\/li>\n
\n- Families in which 3 or more relatives are diagnosed with strabismus, including but not limited to esotropia, infantile esotropia, accommodative esotropia, intermittent esotropia, and exotropia.<\/li>\n<\/ul>\n<\/ul>\n
The conditions we study generally cause symptoms that are noted in infancy or early childhood, even if an official diagnosis is not made for several years. If symptoms begin in adulthood or are due to surgery or trauma, our study is unlikely to be appropriate.\u00a0 Please do not hesitate to contact us with questions about eligibility.<\/p>\n
What participation includes:<\/h3>\n\n- All participation steps can be arranged remotely. Travel to Boston is not required.<\/li>\n
- There are no fees nor costs to participate.<\/li>\n
- We can explain the study and enrollment process and answer any questions via telephone, video conferencing, or secure email. If a potential participant is being seen at Boston Children\u2019s Hospital, we may also be able to meet in person.<\/li>\n
- Enrollment is ongoing and rolling with no predetermined end date.<\/li>\n
- Our goal is to enroll all affected and unaffected close members of a family (such as parents and siblings) when feasible.<\/li>\n
- Enrollment consists of four steps: 1) Screening, 2) Consenting, 3) Request for medical records, imaging, and test results, and 4) Sampling.<\/li>\n<\/ul>\n
1. Screening<\/h4>\n
Receiving initial information about potential participants through a screening form allows us to determine if enrollment in our study is appropriate.\u00a0 We gather this information through an Intake Form<\/a>\u00a0that can be downloaded or collected by phone. Once completed, please return the form via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a><\/p>\n2. Consenting<\/h4>\n
Informed consent from each participant is obtained. Informed consent is a legal term. It means that the potential participant is fully aware of the facts and risks of participating in the research study before agreeing to it. An Engle Lab staff member will obtain consent by phone or videoconference. This session provides an opportunity for the potential participant and family to ask questions and for us to be sure that everyone is aware of the study process. For minors or people under guardianship, in addition to consent, we may obtain assent from the participant. For families with appointments at Boston Children\u2019s Hospital, in-person consenting may also be an option.\u00a0 Depending on the discussion and number of questions, the consenting process typically takes 10-20 minutes.\u00a0 Participants are given an opportunity to read the consent carefully prior to the discussion, and forms can be emailed directly and\/or included in an enrollment kit.\u00a0 Once all questions have been satisfactorily addressed and consenting has been completed and is on file, we move on to sampling.<\/p>\n
3. Request for medical records, imaging, and test results<\/h4>\n
In addition to the initial intake form, we require additional clinical information to successfully study an enrolled individual or family.\u00a0 This information can be obtained throughout the enrollment and participation process. We request that the participants fill out the forms below: clinical history form, medical history form, and medical records release form that provide permission for us to request medical records and copies of imaging studies (typically MRI scans). Please note that some facilities require that patients use that facility\u2019s specific release form; information on our form should help you to complete any requests to share records with us. We also ask for photos and videos of eye and facial movements (some of which can be done online). Please download these forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a>\u00a0Links to additional forms including a sample consent are also available in the FAQs below.<\/p>\nWhat forms or information are required?\u00a0<\/em><\/h5>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
4. Sampling<\/h4>\n
The Engle Lab genetic studies typically require a saliva or blood sample from each participant.\u00a0 Once received by the lab, this sample is used to extract DNA. Saliva samples can be obtained in the comfort of the home, using special collection tubes that we can mail, along with some paperwork, directly to you or to your doctor\u2019s office. These samples and paperwork are then returned to the lab using our mailers at our cost.\u00a0 As with the other steps, if you are receiving care at Boston Children\u2019s Hospital, we can arrange to meet with you in person to complete sampling. On rare occasions when the lab cannot successfully obtain adequate DNA from a sample, we may need to request a repeat saliva sample or an alternative sample, such as via a blood draw.\u00a0 On other rare occasions a participant may prefer to provide a blood sample rather than a saliva sample.<\/p>\n
Please do not hesitate to contact us with any questions about the enrollment process.<\/strong><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
BACK TO TOP ^<\/a><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ module_id=”CCDDClinic” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/2012_Chair-celebration_Engle-Hunter.jpg” title_text=”2012_Chair celebration_Engle-Hunter” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. Elizabeth Engle and Dr. David Hunter.<\/em><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/3.-patient-study-button-scaled.jpg” title_text=”3. patient & study button” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. David Hunter and Sarah Mackinnon (orthoptist) evaluating a patient at the Moebius Syndrome Foundation (MSF) Annual Meeting.<\/em><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.9.7″]<\/p>\n
Attending the Ocular CCDD Clinic<\/h2>\n
Elizabeth Engle<\/a> MD (Neurologist),\u00a0David Hunter<\/a>\u00a0 MD, PhD (Ophthalmologist-in-Chief),\u00a0Sarah MacKinnon<\/a>\u00a0MSc, OC(C), CO, COMT (Chief Orthoptist) and Brenda Barry<\/a>\u00a0MS CGC (Genetic Counselor) hold a combined outpatient clinic in which they evaluate individuals of all ages who have, or may have, an ocular CCDD.<\/p>\nCCDD clinic patients undergo ophthalmological and neurological consultations. Diagnosis, etiologies, prognosis, treatment options, genetic testing, and research enrollment options may be discussed at the clinic visit. Drs. Hunter and Engle will both be present to answer questions and address concerns.<\/p>\n
Appointments generally last 3 to 4 hours and the clinic is typically held the first Monday afternoon of the month in the Ophthalmology Department, Fegan 4, Boston Children\u2019s Hospital main campus, 300 Longwood Avenue, Boston, MA.<\/p>\n
Screening<\/h3>\n
We request information in advance of CCDD clinic visits. This information allows us to be certain that the patient is seen by the correct specialists and allows us to review the patient\u2019s history in advance. If you or a family member or patient wishes to be screened for CCDD clinic, please download and fill out the four forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail<\/a>.<\/p>\n\n- Intake Form<\/a><\/li>\n
- Clinical History Form<\/a><\/span><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
Please contact englegc.research@childrens.harvard.edu<\/a>\u00a0for more information about the CCDD clinic and\/or to schedule an appointment.\u00a0 If an appointment is appropriate, you will be connected with administrative staff at the hospital to obtain a medical records number and to receive help regarding any billing and insurance questions.<\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
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Frequently Asked Questions (FAQs)<\/h2>\nWhat is strabismus?<\/em><\/h4>\nStrabismus refers to eyes that are misaligned.\u00a0 This misalignment, or inability of the eyes to coordinate movements, may be present from infancy or develop over time and is thought to affect 1-5% of the general population.\u00a0 We are still learning about strabismus, but we know it can be caused by problems with the eye muscles, the nerves that control these muscles, or problems with how the brain processes visual information.\u00a0 The Engle Lab studies familial strabismus of all types and complex strabismus syndromes that are present from birth or infancy.<\/p>\n
What is a CCDD?\u00a0<\/em><\/h4>\nCongenital Cranial Dysinnervation Disorders (CCDDs) are neurological conditions affecting one or more of the cranial motor nerves. The cranial motor nerves develop from the brain and connect to muscles and tissues to control functions such as movement of the eyes and eyelids, facial expression, blinking, chewing, and swallowing. CCDDs that impact eye movements, and often cause strabismus, are called ocular CCDDs.\u00a0 Ocular CCDDs include CFEOM (congenital fibrosis of extraocular muscles), Duane syndrome, 3rd, 4th, and 6th nerve palsy, Moebius syndrome, ocular synkinesis syndromes and horizontal gaze palsy with progressive scoliosis (HGPPS). Other CCDDs most prominently affect facial movements, resulting in congenital facial weakness.<\/p>\n
What genes are studied by the Engle Lab?<\/em><\/h4>\nThe Engle Lab has identified, characterized, and continues to study multiple genetic disorders that alter the development and function of the nerves and muscles critical for typical eye and facial movements.\u00a0 Some of the molecules and pathways we study are related to mutations in the following genes: KIF21A, TUBB3, TUBB2B, <\/em>and PHOX2A<\/em> that cause CFEOM; \u00a0CHN1, MAFB, HOXA1,<\/em> SALL4, <\/em>and ROBO3\u00a0 <\/em>that cause Duane syndrome \/ horizontal gaze palsy; and HOXB1 <\/em>that causes congenital facial weakness.<\/p>\nThe Engle Lab is also focused on identifying new, previously uncharacterized genetic causes of CCDDs.\u00a0 For this reason, our set-up and methods differ from those of commercial testing labs that exist to precisely test known genes.\u00a0 If your health care provider feels that a known genetic condition may explain the symptoms you or a family member are experiencing, genetic testing for that condition may now be commercially available because of past research successes.\u00a0 If so, it may be more efficient to directly pursue that testing in a clinical lab rather than enrolling in a research study that has an uncertain timeline for results and the need for repeated sampling and confirmation testing.<\/p>\n
Is there a cost to participants?<\/em><\/h4>\nThere is no cost to participate and travel is not required. There is also no compensation for participation in our study.<\/p>\n
What are the goals of the study?<\/em><\/h4>\nWe use DNA from participants to identify and study new genetic causes of CCDDs and impaired eye and facial movements. The clinical information helps us to understand what a gene does normally and what can result if it is mutated and thus not working normally. From a clinical standpoint, by understanding the genetic cause of a given CCDD we hope to improve diagnosis and treatment, and to provide accurate genetic counseling.<\/p>\n
What is the enrollment process?<\/em><\/h4>\nWe welcome contact by email, phone, or postal mail<\/a> from patients, parents, and healthcare providers to determine if someone is eligible for the study.\u00a0 Once we receive an inquiry and screening forms, research staff contact you to discuss enrollment or request additional information, review the consent form, and guide the sampling process.<\/p>\nWhat type of medical information is helpful?<\/em><\/h4>\nWe benefit from collecting details through interviews and forms completed by patients themselves or their health care providers, as well as through receipt of primary medical records.\u00a0 Typically, of greatest help are records related to ophthalmology, neurology, and genetics, including exam and surgical notes, testing results, and copies of brain\/eye imaging (especially MRI scans). We can also provide a link to an online web app, StrabisPIX<\/a>, developed by our colleagues in Ophthalmology at Boston Children\u2019s Hospital to capture photographs of eye positions.<\/p>\nWhat types of samples are needed for participation?<\/em><\/h4>\nWe generally start by obtaining DNA using a specialized saliva collection kit that we provide to families.\u00a0 Sometimes we may ask for a blood draw if collection of DNA using saliva is not successful or if we have a specific need for whole blood.\u00a0 We may also obtain already stored DNA and\/or tissue that may have been collected through a doctor\u2019s office and is no longer needed.\u00a0 Most commonly, only one sample is required.\u00a0 However, if the DNA is of poor quality, is used up over the course of the research, or we have a specialized project, we may reach out to enrolled participants to request additional samples, if they have provided consent for us to recontact them.<\/p>\n
Who can participate?<\/em><\/h4>\nWe need to enroll and obtain DNA from at least one family member diagnosed with a condition we study.\u00a0 If only one person in the family has the condition, we would likely request that the person\u2019s parents and siblings also enroll. If more than one person in the family has the condition, we would likely ask if all affected individuals and their immediate family members would enroll.\u00a0 This allows us to compare changes we find in the DNA of the persons with the diagnosis to the DNA of unaffected family members to best interpret genetic findings.\u00a0 However, we acknowledge that enrolling additional biological relatives is not always feasible. Importantly, we must consent each participant and receive their sample.<\/p>\n
What forms or information are required?\u00a0<\/em><\/h4>\nWe ask to receive back a general intake and 3 initial forms from people interested in the study. Other materials, including the consent and submission form, are provided by email and\/or with the enrollment kit. These forms may be downloaded by clicking below.\u00a0 They can be completed and returned by email<\/a> or regular mail<\/a>.<\/p>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n
- Example Consent (this is an example and should not be used for enrollment)<\/span><\/a><\/li>\n
- Sample Submission Form<\/span><\/a><\/li>\n
- Participant Questionnaire (PQ)<\/span><\/a><\/li>\n<\/ul>\n
Are study participation and results confidential?<\/em><\/h4>\nOur lab collects DNA samples and medical information from persons and families with features indicating they have or may have a CCDD or familial strabismus.\u00a0 The information is kept confidential.\u00a0 Identifiable details are not shared with anyone outside of the Engle Lab without the specific permission of participants.\u00a0 No results are placed in the medical record of participating individuals or their families prior to clinical confirmation. We consent people to make sure everyone understands important details of the study and how we protect participant data.<\/p>\n
Can participants obtain results?<\/em><\/h4>\nAnalyses will be done in our research laboratory and so are considered investigational. This means that we cannot directly release results to a participant. However, participants can call or email us at any time to ask questions or to check in on the overall progress of the program. In addition, participants are given choices on the consent form to indicate if s\/he wishes to be informed about the availability of results. If we identify findings for a specific participant who has noted s\/he wished to be informed of significant results, we would attempt to contact the participant and\/or a designated medical provider (based on information obtained during enrollment or as updated by the participant).\u00a0 We would work with them to have our research findings confirmed by an authorized clinical laboratory which would then issue a report that would become part of the medical record and provide details about the results.\u00a0Our research findings are also shared through scientific publications. The results in such publications do not include any information that would permit identification of participants. We can provide copies of these publications on request.<\/p>\n
What are possible benefits of participation?<\/em><\/h4>\nEach and every participant contributes to the improved understanding of the CCDDs.\u00a0 Some participants may also learn about the genetic basis of their condition.<\/p>\n
How can I tell other people about this study?<\/em><\/h4>\nYou may tell people about this website and share all of our contact information with anyone you wish. You may also download and share\u00a0these pamphlets\u00a0about the research on cranial nerves<\/a> and on facial weakness and Moebius syndrome.<\/a><\/span><\/p>\n<\/em><\/h4>\n<\/em><\/h4>\nWhat other resources exist?<\/em><\/h4>\n\n- Adult Strabismus Q&A with Dr. Hunter<\/a><\/li>\n
- Clinical Trials<\/a><\/li>\n
- Boston Children\u2019s Hospital Clinical Trials<\/a><\/li>\n
- GeneReviews CFEOM<\/a><\/li>\n
- GeneReviews Duane Syndrome<\/a><\/li>\n
- Moebius Syndrome Foundation<\/a><\/li>\n<\/ul>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
BACK TO TOP ^<\/a><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"
The Engle Lab at the F.M. Kirby Neurobiology Center Patient & Study Participant ResourcesWelcome, we are glad you found us!\u00a0 You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information […]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\n
[et_pb_section fb_built=\"1\" admin_label=\"BKGD IMAGE\" _builder_version=\"4.5.0\" background_color=\"#000000\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" background_enable_image=\"off\" background_size=\"initial\" custom_padding=\"1px|0px|0|0px|false|false\" global_module=\"3860\" saved_tabs=\"all\"][et_pb_row _builder_version=\"4.5.0\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" min_height=\"353px\" custom_margin=\"|auto||161px||\" custom_padding=\"17px|0px|255px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"home_header\" _builder_version=\"4.5.0\" text_font=\"||||||||\" header_font=\"||||||||\" min_height=\"39px\" custom_css_main_element=\"color:#ffffff;||line-height:0.95em;||font-family:el messiri;||font-size:44px;||font-weight:normal;\" inline_fonts=\"Merriweather,El Messiri,Georgia\"]<\/div>\n<\/div>\nThe Engle Lab<\/div>\nat the FM Kirby Neurobiology Center<\/div>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"4.4.5\" background_color=\"#ffffff\" custom_padding=\"0|0px|0|0px|false|false\"][et_pb_row _builder_version=\"4.3.4\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text _builder_version=\"4.4.5\"]<\/span><\/p>\nScience & Research<\/span><\/p>[\/et_pb_text][et_pb_text _builder_version=\"4.4.5\"]For a full list of Engle Lab publications, please click here<\/a>. To request a PDF of a lab publication, email engle.admin@childrens.harvard.edu<\/a>.<\/p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"3.22.3\" custom_padding=\"0|0px|47.625px|0|false|false\"][et_pb_row column_structure=\"1_3,1_3,1_3\" _builder_version=\"4.5.0\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"1_3\" _builder_version=\"4.5.0\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#CCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" background_enable_color=\"off\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] ![\"Image\"](\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/CCDD-image.001-3.jpeg\")
CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#Transcriptomics\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] ![\"Image\"](\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/MR-scRNAseq-tSNE-30x30-1.jpg\")
Transcriptomic and Epigenomic Analyses of the Developing Brainstem<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsCCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] ![\"Image\"](\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2019\/02\/grey-tile-1.jpg\")
Genetics & Genomics of CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Disease Modeling<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsEsotropiaExotropia\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of Esotropia & Exotropia<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Imaging<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=\"topic-two\" _builder_version=\"3.25\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_divider _builder_version=\"3.23.4\" height=\"0px\"][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=\"1_2,1_2\" module_id=\"CCDDs\" _builder_version=\"4.5.0\" custom_padding=\"30px|0px|25.2344px|0px|false|false\" link_option_url=\"#CCDDs\"][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_image src=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/CCDD-image.001-2.jpeg\" title_text=\"CCDD image.001\" align_tablet=\"center\" align_phone=\"\" align_last_edited=\"on|desktop\" _builder_version=\"4.5.0\"][\/et_pb_image][et_pb_text _builder_version=\"3.27.4\" text_font=\"||||||||\" text_font_size=\"1px\" custom_margin=\"-20px||\" custom_padding=\"0px||\"]Optional image caption and attribution<\/em><\/p>[\/et_pb_text][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]Publications<\/h3>\n
Publication 1 ><\/p>\n
Publication 2 ><\/p>[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]
Congenital Cranial Dysinnervation Disorders (CCDDs)<\/h2>\n
We humans are defined, in part, by the nuanced and coordinated ocular and facial movements that are fundamental to our vision and social communication. The Engle Lab studies human developmental disorders that perturb these eye and face movements as a framework to understand how neurons are specified and how cranial neural circuits are formed. We identify human disorders of eye and face movement, define their genetic etiologies, and study the developmental pathology and disease mechanism in vitro and in animal models. We also study the normal development of cranial motor neurons and their axonal processes. Our research has led to the definition of the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are birth defects in which cranial motor neurons or their axonal processes fail to develop correctly. While the CCDDs include all cranial motor nerves, the lab focuses in particular on disorders of oculomotor (cranial nerve 3), trochlear (cranial nerve 4), abducens (cranial nerve 6) and\/or facial (cranial nerve 7) development. The ocular CCDDs result in the inability to raise the eyelid(s) or to move the eye(s) in one or more directions of gaze. The facial CCDDs result in unilateral or bilateral h bvdsafacial weakness. We also study the genetics of esotropia and exotropia (common or comitant forms of strabismus), as described below<\/a>.<\/span><\/p>\nThe lab has found that human disorders of cranial motor neuron development provide a unique and powerful system to study Mendelian genetics and neural connectivity:<\/span><\/p>\n\n- Each cranial motor nucleus contains a small number of motor neurons.<\/span><\/li>\n
- Each cranial motor nerve has straightforward tractable developmental anatomy that can be visualized in three dimensions.<\/span><\/li>\n
- Errors in development result in human phenotypes that are present at birth, lifelong, visible to the examiner, and stereotypic in presentation.<\/span><\/li>\n
- All higher vertebrates have 12 highly conserved cranial nerves, providing consistent translation to model organisms for developmental and mechanistic studies.<\/span><\/li>\n
- The Engle Lab has amassed a remarkable Mendelian cohort of research participants, leading to a high likelihood that we will identify multiple disease alleles with which to document causality of a new genetic disorder.<\/span><\/li>\n<\/ul>[\/et_pb_text][et_pb_text _builder_version=\"3.27.4\"]
<\/span><\/h1>\nThe Engle Lab<\/span><\/h1>\nat the F.M. Kirby Neurobiology Center<\/span><\/h2>\n<\/span><\/h1>\n<\/span><\/h1>\n<\/h1>\n<\/span><\/strong><\/h2>\n[\/et_pb_text][et_pb_text _builder_version=”4.5.0″ width=”163%” max_width=”100%” custom_margin=”|-989px||||” custom_padding=”7px|40px||103px|false|false”]<\/p>\n
<\/span><\/p>\nPatient & Study Participant Resources<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.5.3″ custom_padding=”0|0px|47.625px|0|false|false”][et_pb_row _builder_version=”4.5.0″ _module_preset=”default” custom_padding=”||0px|||”][et_pb_column type=”4_4″ _builder_version=”4.5.0″ _module_preset=”default”][et_pb_text _builder_version=”4.5.3″ _module_preset=”default”]<\/p>\n
Welcome, we are glad you found us!\u00a0<\/strong><\/h2>\nYou may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information will address questions you may have about enrolling in our research and\/or attending our CCDD Consultation Clinic.<\/p>\n
From a research standpoint, the Engle Lab strives to better understand the neurogenetic basis of cranial nerve development and function.\u00a0 This is done through gene discovery and basic research described in the Science section<\/a> of our website. Gene discovery requires the enrollment and participation of individuals and families diagnosed with rare conditions involving atypical or limited eye and facial movements. These conditions include both defined or undefined congenital cranial dysinnervation disorders (CCDDs)<\/a>\u00a0and familial strabismus<\/a>.<\/p>\nDr. Engle and her colleagues also oversee and participate in a multi-disciplinary, second-opinion consultation clinic at Boston Children\u2019s Hospital for children and adults diagnosed with ocular CCDDs. This clinic is staffed by two physicians, Dr. Elizabeth Engle, a child neurologist and pediatrician, and Dr. David Hunter, an ophthalmologist, as well as an\u00a0orthoptist <\/a>and genetic counselor<\/a>.\u00a0More information on this clinic is provided in\u00a0\u00a0“Attending the Ocular CCDD Clinic”<\/a>.<\/p>\n\n- See our FAQs section<\/a> for definitions and additional background.<\/li>\n<\/ul>\n
How can I participate or become involved?<\/h2>\n
There is overlap between the conditions studied by the Engle Lab and the conditions seen through the CCDD clinic at Boston Children\u2019s Hospital.\u00a0 However, the research and formal medical evaluations are performed through separate programs. People can choose to participate in, and be appropriate for, one or both options.\u00a0 To pre-screen individuals for either program (research enrollment or clinic visit), Dr. Engle and her team review clinical information provided through forms and medical records. This helps us to be sure that the desired study and\/or clinic participation are appropriate.<\/p>\n
Continue reading below to learn more or click on the buttons to move to a specific section.<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.9.7″ custom_margin=”0px|auto|0px|auto|false|false” custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_3″ _builder_version=”4.5.0″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#CCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ background_enable_color=”off” max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
<\/p>\n<\/p>\nEnrolling Into Our Research<\/div>\n <\/div>\n
<\/a><\/div>\n
[\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsCCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
<\/p>\n<\/p>\nAttending Ocular CCDD Clinic<\/div>\n <\/div>\n
<\/a><\/div>\n
[\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsEsotropiaExotropia” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
<\/p>\n<\/p>\nFrequently Asked Questions (FAQs)<\/div>\n <\/div>\n
<\/a><\/div>\n
[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”Enrolling” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” link_option_url=”#CCDDs” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/08\/new.MBS_.lab_.jpg” title_text=”new.MBS.lab” align=”center” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″ width=”57%” module_alignment=”center” height=”362px”][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” width=”100%” custom_margin=”-20px||” custom_padding=”0px|||217px|false|false”]<\/p>\n
Dr. Elizabeth Engle (center, front) and members of the Engle Lab commemorating Moebius Syndrome Awareness Day 2020.<\/em><\/p>\n[\/et_pb_text][et_pb_text module_id=”genetics” _builder_version=”4.5.3″ max_width=”100%” custom_margin=”|-571px||||”]<\/p>\n
Enrolling in Engle Lab Research Studies<\/h2>\n
The Engle Lab\u2019s research enrollment goals are to (1) enroll participants who are born with complex eye and facial movement disorders or disorders of lower cranial nerve function together with family members and\u00a0 (2) enroll families in which three or more relatives are diagnosed with strabismus.\u00a0 Patients, parents, health care providers and other researchers all refer individuals to us for enrollment.<\/p>\n
Examples of disorders we study:<\/h3>\n\n- Complex congenital eye and eyelid movement disorders:<\/li>\n
\n- Congenital Fibrosis of the Extraocular Muscles (CFEOM)<\/li>\n
- Congenital ptosis<\/li>\n
- Marcus Gunn Jaw Winking syndrome (MGJWS)<\/li>\n
- Duane syndrome \/ Duane retraction syndrome (DRS)<\/li>\n
- Horizontal Gaze Palsy (HGP)<\/li>\n
- Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)<\/li>\n
- Moebius syndrome \/ Moebius sequence (MBS)<\/li>\n
- Congenital 3rd, 4th, or 6th nerve palsy<\/li>\n
- Ocular and lid synkinesis<\/li>\n
- Any other complex congenital eye or lid movement disorder (yet to be defined)<\/li>\n<\/ul>\n
- Congenital facial weakness or palsy<\/li>\n
\n- Isolated congenital facial weakness<\/li>\n
- Syndromic congenital facial weakness<\/li>\n
- Moebius syndrome<\/li>\n<\/ul>\n
- Congenital disorders of lower cranial nerves<\/li>\n
\n- Examples include disorders of tongue movement, chewing, or swallowing<\/li>\n<\/ul>\n
- Familial Strabismus<\/li>\n
\n- Families in which 3 or more relatives are diagnosed with strabismus, including but not limited to esotropia, infantile esotropia, accommodative esotropia, intermittent esotropia, and exotropia.<\/li>\n<\/ul>\n<\/ul>\n
The conditions we study generally cause symptoms that are noted in infancy or early childhood, even if an official diagnosis is not made for several years. If symptoms begin in adulthood or are due to surgery or trauma, our study is unlikely to be appropriate.\u00a0 Please do not hesitate to contact us with questions about eligibility.<\/p>\n
What participation includes:<\/h3>\n\n- All participation steps can be arranged remotely. Travel to Boston is not required.<\/li>\n
- There are no fees nor costs to participate.<\/li>\n
- We can explain the study and enrollment process and answer any questions via telephone, video conferencing, or secure email. If a potential participant is being seen at Boston Children\u2019s Hospital, we may also be able to meet in person.<\/li>\n
- Enrollment is ongoing and rolling with no predetermined end date.<\/li>\n
- Our goal is to enroll all affected and unaffected close members of a family (such as parents and siblings) when feasible.<\/li>\n
- Enrollment consists of four steps: 1) Screening, 2) Consenting, 3) Request for medical records, imaging, and test results, and 4) Sampling.<\/li>\n<\/ul>\n
1. Screening<\/h4>\n
Receiving initial information about potential participants through a screening form allows us to determine if enrollment in our study is appropriate.\u00a0 We gather this information through an Intake Form<\/a>\u00a0that can be downloaded or collected by phone. Once completed, please return the form via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a><\/p>\n2. Consenting<\/h4>\n
Informed consent from each participant is obtained. Informed consent is a legal term. It means that the potential participant is fully aware of the facts and risks of participating in the research study before agreeing to it. An Engle Lab staff member will obtain consent by phone or videoconference. This session provides an opportunity for the potential participant and family to ask questions and for us to be sure that everyone is aware of the study process. For minors or people under guardianship, in addition to consent, we may obtain assent from the participant. For families with appointments at Boston Children\u2019s Hospital, in-person consenting may also be an option.\u00a0 Depending on the discussion and number of questions, the consenting process typically takes 10-20 minutes.\u00a0 Participants are given an opportunity to read the consent carefully prior to the discussion, and forms can be emailed directly and\/or included in an enrollment kit.\u00a0 Once all questions have been satisfactorily addressed and consenting has been completed and is on file, we move on to sampling.<\/p>\n
3. Request for medical records, imaging, and test results<\/h4>\n
In addition to the initial intake form, we require additional clinical information to successfully study an enrolled individual or family.\u00a0 This information can be obtained throughout the enrollment and participation process. We request that the participants fill out the forms below: clinical history form, medical history form, and medical records release form that provide permission for us to request medical records and copies of imaging studies (typically MRI scans). Please note that some facilities require that patients use that facility\u2019s specific release form; information on our form should help you to complete any requests to share records with us. We also ask for photos and videos of eye and facial movements (some of which can be done online). Please download these forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a>\u00a0Links to additional forms including a sample consent are also available in the FAQs below.<\/p>\nWhat forms or information are required?\u00a0<\/em><\/h5>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
4. Sampling<\/h4>\n
The Engle Lab genetic studies typically require a saliva or blood sample from each participant.\u00a0 Once received by the lab, this sample is used to extract DNA. Saliva samples can be obtained in the comfort of the home, using special collection tubes that we can mail, along with some paperwork, directly to you or to your doctor\u2019s office. These samples and paperwork are then returned to the lab using our mailers at our cost.\u00a0 As with the other steps, if you are receiving care at Boston Children\u2019s Hospital, we can arrange to meet with you in person to complete sampling. On rare occasions when the lab cannot successfully obtain adequate DNA from a sample, we may need to request a repeat saliva sample or an alternative sample, such as via a blood draw.\u00a0 On other rare occasions a participant may prefer to provide a blood sample rather than a saliva sample.<\/p>\n
Please do not hesitate to contact us with any questions about the enrollment process.<\/strong><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
BACK TO TOP ^<\/a><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ module_id=”CCDDClinic” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/2012_Chair-celebration_Engle-Hunter.jpg” title_text=”2012_Chair celebration_Engle-Hunter” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. Elizabeth Engle and Dr. David Hunter.<\/em><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/3.-patient-study-button-scaled.jpg” title_text=”3. patient & study button” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. David Hunter and Sarah Mackinnon (orthoptist) evaluating a patient at the Moebius Syndrome Foundation (MSF) Annual Meeting.<\/em><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.9.7″]<\/p>\n
Attending the Ocular CCDD Clinic<\/h2>\n
Elizabeth Engle<\/a> MD (Neurologist),\u00a0David Hunter<\/a>\u00a0 MD, PhD (Ophthalmologist-in-Chief),\u00a0Sarah MacKinnon<\/a>\u00a0MSc, OC(C), CO, COMT (Chief Orthoptist) and Brenda Barry<\/a>\u00a0MS CGC (Genetic Counselor) hold a combined outpatient clinic in which they evaluate individuals of all ages who have, or may have, an ocular CCDD.<\/p>\nCCDD clinic patients undergo ophthalmological and neurological consultations. Diagnosis, etiologies, prognosis, treatment options, genetic testing, and research enrollment options may be discussed at the clinic visit. Drs. Hunter and Engle will both be present to answer questions and address concerns.<\/p>\n
Appointments generally last 3 to 4 hours and the clinic is typically held the first Monday afternoon of the month in the Ophthalmology Department, Fegan 4, Boston Children\u2019s Hospital main campus, 300 Longwood Avenue, Boston, MA.<\/p>\n
Screening<\/h3>\n
We request information in advance of CCDD clinic visits. This information allows us to be certain that the patient is seen by the correct specialists and allows us to review the patient\u2019s history in advance. If you or a family member or patient wishes to be screened for CCDD clinic, please download and fill out the four forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail<\/a>.<\/p>\n\n- Intake Form<\/a><\/li>\n
- Clinical History Form<\/a><\/span><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
Please contact englegc.research@childrens.harvard.edu<\/a>\u00a0for more information about the CCDD clinic and\/or to schedule an appointment.\u00a0 If an appointment is appropriate, you will be connected with administrative staff at the hospital to obtain a medical records number and to receive help regarding any billing and insurance questions.<\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
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Frequently Asked Questions (FAQs)<\/h2>\nWhat is strabismus?<\/em><\/h4>\nStrabismus refers to eyes that are misaligned.\u00a0 This misalignment, or inability of the eyes to coordinate movements, may be present from infancy or develop over time and is thought to affect 1-5% of the general population.\u00a0 We are still learning about strabismus, but we know it can be caused by problems with the eye muscles, the nerves that control these muscles, or problems with how the brain processes visual information.\u00a0 The Engle Lab studies familial strabismus of all types and complex strabismus syndromes that are present from birth or infancy.<\/p>\n
What is a CCDD?\u00a0<\/em><\/h4>\nCongenital Cranial Dysinnervation Disorders (CCDDs) are neurological conditions affecting one or more of the cranial motor nerves. The cranial motor nerves develop from the brain and connect to muscles and tissues to control functions such as movement of the eyes and eyelids, facial expression, blinking, chewing, and swallowing. CCDDs that impact eye movements, and often cause strabismus, are called ocular CCDDs.\u00a0 Ocular CCDDs include CFEOM (congenital fibrosis of extraocular muscles), Duane syndrome, 3rd, 4th, and 6th nerve palsy, Moebius syndrome, ocular synkinesis syndromes and horizontal gaze palsy with progressive scoliosis (HGPPS). Other CCDDs most prominently affect facial movements, resulting in congenital facial weakness.<\/p>\n
What genes are studied by the Engle Lab?<\/em><\/h4>\nThe Engle Lab has identified, characterized, and continues to study multiple genetic disorders that alter the development and function of the nerves and muscles critical for typical eye and facial movements.\u00a0 Some of the molecules and pathways we study are related to mutations in the following genes: KIF21A, TUBB3, TUBB2B, <\/em>and PHOX2A<\/em> that cause CFEOM; \u00a0CHN1, MAFB, HOXA1,<\/em> SALL4, <\/em>and ROBO3\u00a0 <\/em>that cause Duane syndrome \/ horizontal gaze palsy; and HOXB1 <\/em>that causes congenital facial weakness.<\/p>\nThe Engle Lab is also focused on identifying new, previously uncharacterized genetic causes of CCDDs.\u00a0 For this reason, our set-up and methods differ from those of commercial testing labs that exist to precisely test known genes.\u00a0 If your health care provider feels that a known genetic condition may explain the symptoms you or a family member are experiencing, genetic testing for that condition may now be commercially available because of past research successes.\u00a0 If so, it may be more efficient to directly pursue that testing in a clinical lab rather than enrolling in a research study that has an uncertain timeline for results and the need for repeated sampling and confirmation testing.<\/p>\n
Is there a cost to participants?<\/em><\/h4>\nThere is no cost to participate and travel is not required. There is also no compensation for participation in our study.<\/p>\n
What are the goals of the study?<\/em><\/h4>\nWe use DNA from participants to identify and study new genetic causes of CCDDs and impaired eye and facial movements. The clinical information helps us to understand what a gene does normally and what can result if it is mutated and thus not working normally. From a clinical standpoint, by understanding the genetic cause of a given CCDD we hope to improve diagnosis and treatment, and to provide accurate genetic counseling.<\/p>\n
What is the enrollment process?<\/em><\/h4>\nWe welcome contact by email, phone, or postal mail<\/a> from patients, parents, and healthcare providers to determine if someone is eligible for the study.\u00a0 Once we receive an inquiry and screening forms, research staff contact you to discuss enrollment or request additional information, review the consent form, and guide the sampling process.<\/p>\nWhat type of medical information is helpful?<\/em><\/h4>\nWe benefit from collecting details through interviews and forms completed by patients themselves or their health care providers, as well as through receipt of primary medical records.\u00a0 Typically, of greatest help are records related to ophthalmology, neurology, and genetics, including exam and surgical notes, testing results, and copies of brain\/eye imaging (especially MRI scans). We can also provide a link to an online web app, StrabisPIX<\/a>, developed by our colleagues in Ophthalmology at Boston Children\u2019s Hospital to capture photographs of eye positions.<\/p>\nWhat types of samples are needed for participation?<\/em><\/h4>\nWe generally start by obtaining DNA using a specialized saliva collection kit that we provide to families.\u00a0 Sometimes we may ask for a blood draw if collection of DNA using saliva is not successful or if we have a specific need for whole blood.\u00a0 We may also obtain already stored DNA and\/or tissue that may have been collected through a doctor\u2019s office and is no longer needed.\u00a0 Most commonly, only one sample is required.\u00a0 However, if the DNA is of poor quality, is used up over the course of the research, or we have a specialized project, we may reach out to enrolled participants to request additional samples, if they have provided consent for us to recontact them.<\/p>\n
Who can participate?<\/em><\/h4>\nWe need to enroll and obtain DNA from at least one family member diagnosed with a condition we study.\u00a0 If only one person in the family has the condition, we would likely request that the person\u2019s parents and siblings also enroll. If more than one person in the family has the condition, we would likely ask if all affected individuals and their immediate family members would enroll.\u00a0 This allows us to compare changes we find in the DNA of the persons with the diagnosis to the DNA of unaffected family members to best interpret genetic findings.\u00a0 However, we acknowledge that enrolling additional biological relatives is not always feasible. Importantly, we must consent each participant and receive their sample.<\/p>\n
What forms or information are required?\u00a0<\/em><\/h4>\nWe ask to receive back a general intake and 3 initial forms from people interested in the study. Other materials, including the consent and submission form, are provided by email and\/or with the enrollment kit. These forms may be downloaded by clicking below.\u00a0 They can be completed and returned by email<\/a> or regular mail<\/a>.<\/p>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n
- Example Consent (this is an example and should not be used for enrollment)<\/span><\/a><\/li>\n
- Sample Submission Form<\/span><\/a><\/li>\n
- Participant Questionnaire (PQ)<\/span><\/a><\/li>\n<\/ul>\n
Are study participation and results confidential?<\/em><\/h4>\nOur lab collects DNA samples and medical information from persons and families with features indicating they have or may have a CCDD or familial strabismus.\u00a0 The information is kept confidential.\u00a0 Identifiable details are not shared with anyone outside of the Engle Lab without the specific permission of participants.\u00a0 No results are placed in the medical record of participating individuals or their families prior to clinical confirmation. We consent people to make sure everyone understands important details of the study and how we protect participant data.<\/p>\n
Can participants obtain results?<\/em><\/h4>\nAnalyses will be done in our research laboratory and so are considered investigational. This means that we cannot directly release results to a participant. However, participants can call or email us at any time to ask questions or to check in on the overall progress of the program. In addition, participants are given choices on the consent form to indicate if s\/he wishes to be informed about the availability of results. If we identify findings for a specific participant who has noted s\/he wished to be informed of significant results, we would attempt to contact the participant and\/or a designated medical provider (based on information obtained during enrollment or as updated by the participant).\u00a0 We would work with them to have our research findings confirmed by an authorized clinical laboratory which would then issue a report that would become part of the medical record and provide details about the results.\u00a0Our research findings are also shared through scientific publications. The results in such publications do not include any information that would permit identification of participants. We can provide copies of these publications on request.<\/p>\n
What are possible benefits of participation?<\/em><\/h4>\nEach and every participant contributes to the improved understanding of the CCDDs.\u00a0 Some participants may also learn about the genetic basis of their condition.<\/p>\n
How can I tell other people about this study?<\/em><\/h4>\nYou may tell people about this website and share all of our contact information with anyone you wish. You may also download and share\u00a0these pamphlets\u00a0about the research on cranial nerves<\/a> and on facial weakness and Moebius syndrome.<\/a><\/span><\/p>\n<\/em><\/h4>\n<\/em><\/h4>\nWhat other resources exist?<\/em><\/h4>\n\n- Adult Strabismus Q&A with Dr. Hunter<\/a><\/li>\n
- Clinical Trials<\/a><\/li>\n
- Boston Children\u2019s Hospital Clinical Trials<\/a><\/li>\n
- GeneReviews CFEOM<\/a><\/li>\n
- GeneReviews Duane Syndrome<\/a><\/li>\n
- Moebius Syndrome Foundation<\/a><\/li>\n<\/ul>\n
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The Engle Lab at the F.M. Kirby Neurobiology Center Patient & Study Participant ResourcesWelcome, we are glad you found us!\u00a0 You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information […]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\n
[et_pb_section fb_built=\"1\" admin_label=\"BKGD IMAGE\" _builder_version=\"4.5.0\" background_color=\"#000000\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" background_enable_image=\"off\" background_size=\"initial\" custom_padding=\"1px|0px|0|0px|false|false\" global_module=\"3860\" saved_tabs=\"all\"][et_pb_row _builder_version=\"4.5.0\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" min_height=\"353px\" custom_margin=\"|auto||161px||\" custom_padding=\"17px|0px|255px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"home_header\" _builder_version=\"4.5.0\" text_font=\"||||||||\" header_font=\"||||||||\" min_height=\"39px\" custom_css_main_element=\"color:#ffffff;||line-height:0.95em;||font-family:el messiri;||font-size:44px;||font-weight:normal;\" inline_fonts=\"Merriweather,El Messiri,Georgia\"]<\/div>\n<\/div>\nThe Engle Lab<\/div>\nat the FM Kirby Neurobiology Center<\/div>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"4.4.5\" background_color=\"#ffffff\" custom_padding=\"0|0px|0|0px|false|false\"][et_pb_row _builder_version=\"4.3.4\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text _builder_version=\"4.4.5\"]<\/span><\/p>\nScience & Research<\/span><\/p>[\/et_pb_text][et_pb_text _builder_version=\"4.4.5\"]For a full list of Engle Lab publications, please click here<\/a>. To request a PDF of a lab publication, email engle.admin@childrens.harvard.edu<\/a>.<\/p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"3.22.3\" custom_padding=\"0|0px|47.625px|0|false|false\"][et_pb_row column_structure=\"1_3,1_3,1_3\" _builder_version=\"4.5.0\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"1_3\" _builder_version=\"4.5.0\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#CCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" background_enable_color=\"off\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#Transcriptomics\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Transcriptomic and Epigenomic Analyses of the Developing Brainstem<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsCCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Disease Modeling<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsEsotropiaExotropia\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of Esotropia & Exotropia<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Imaging<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=\"topic-two\" _builder_version=\"3.25\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_divider _builder_version=\"3.23.4\" height=\"0px\"][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=\"1_2,1_2\" module_id=\"CCDDs\" _builder_version=\"4.5.0\" custom_padding=\"30px|0px|25.2344px|0px|false|false\" link_option_url=\"#CCDDs\"][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_image src=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/CCDD-image.001-2.jpeg\" title_text=\"CCDD image.001\" align_tablet=\"center\" align_phone=\"\" align_last_edited=\"on|desktop\" _builder_version=\"4.5.0\"][\/et_pb_image][et_pb_text _builder_version=\"3.27.4\" text_font=\"||||||||\" text_font_size=\"1px\" custom_margin=\"-20px||\" custom_padding=\"0px||\"]Optional image caption and attribution<\/em><\/p>[\/et_pb_text][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]Publications<\/h3>\n
Publication 1 ><\/p>\n
Publication 2 ><\/p>[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]
Congenital Cranial Dysinnervation Disorders (CCDDs)<\/h2>\n
We humans are defined, in part, by the nuanced and coordinated ocular and facial movements that are fundamental to our vision and social communication. The Engle Lab studies human developmental disorders that perturb these eye and face movements as a framework to understand how neurons are specified and how cranial neural circuits are formed. We identify human disorders of eye and face movement, define their genetic etiologies, and study the developmental pathology and disease mechanism in vitro and in animal models. We also study the normal development of cranial motor neurons and their axonal processes. Our research has led to the definition of the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are birth defects in which cranial motor neurons or their axonal processes fail to develop correctly. While the CCDDs include all cranial motor nerves, the lab focuses in particular on disorders of oculomotor (cranial nerve 3), trochlear (cranial nerve 4), abducens (cranial nerve 6) and\/or facial (cranial nerve 7) development. The ocular CCDDs result in the inability to raise the eyelid(s) or to move the eye(s) in one or more directions of gaze. The facial CCDDs result in unilateral or bilateral h bvdsafacial weakness. We also study the genetics of esotropia and exotropia (common or comitant forms of strabismus), as described below<\/a>.<\/span><\/p>\nThe lab has found that human disorders of cranial motor neuron development provide a unique and powerful system to study Mendelian genetics and neural connectivity:<\/span><\/p>\n\n- Each cranial motor nucleus contains a small number of motor neurons.<\/span><\/li>\n
- Each cranial motor nerve has straightforward tractable developmental anatomy that can be visualized in three dimensions.<\/span><\/li>\n
- Errors in development result in human phenotypes that are present at birth, lifelong, visible to the examiner, and stereotypic in presentation.<\/span><\/li>\n
- All higher vertebrates have 12 highly conserved cranial nerves, providing consistent translation to model organisms for developmental and mechanistic studies.<\/span><\/li>\n
- The Engle Lab has amassed a remarkable Mendelian cohort of research participants, leading to a high likelihood that we will identify multiple disease alleles with which to document causality of a new genetic disorder.<\/span><\/li>\n<\/ul>[\/et_pb_text][et_pb_text _builder_version=\"3.27.4\"]
at the F.M. Kirby Neurobiology Center<\/span><\/h2>\n<\/span><\/h1>\n<\/span><\/h1>\n<\/h1>\n<\/span><\/strong><\/h2>\n[\/et_pb_text][et_pb_text _builder_version=”4.5.0″ width=”163%” max_width=”100%” custom_margin=”|-989px||||” custom_padding=”7px|40px||103px|false|false”]<\/p>\n
<\/span><\/p>\nPatient & Study Participant Resources<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.5.3″ custom_padding=”0|0px|47.625px|0|false|false”][et_pb_row _builder_version=”4.5.0″ _module_preset=”default” custom_padding=”||0px|||”][et_pb_column type=”4_4″ _builder_version=”4.5.0″ _module_preset=”default”][et_pb_text _builder_version=”4.5.3″ _module_preset=”default”]<\/p>\n
Welcome, we are glad you found us!\u00a0<\/strong><\/h2>\nYou may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information will address questions you may have about enrolling in our research and\/or attending our CCDD Consultation Clinic.<\/p>\n
From a research standpoint, the Engle Lab strives to better understand the neurogenetic basis of cranial nerve development and function.\u00a0 This is done through gene discovery and basic research described in the Science section<\/a> of our website. Gene discovery requires the enrollment and participation of individuals and families diagnosed with rare conditions involving atypical or limited eye and facial movements. These conditions include both defined or undefined congenital cranial dysinnervation disorders (CCDDs)<\/a>\u00a0and familial strabismus<\/a>.<\/p>\nDr. Engle and her colleagues also oversee and participate in a multi-disciplinary, second-opinion consultation clinic at Boston Children\u2019s Hospital for children and adults diagnosed with ocular CCDDs. This clinic is staffed by two physicians, Dr. Elizabeth Engle, a child neurologist and pediatrician, and Dr. David Hunter, an ophthalmologist, as well as an\u00a0orthoptist <\/a>and genetic counselor<\/a>.\u00a0More information on this clinic is provided in\u00a0\u00a0“Attending the Ocular CCDD Clinic”<\/a>.<\/p>\n\n- See our FAQs section<\/a> for definitions and additional background.<\/li>\n<\/ul>\n
How can I participate or become involved?<\/h2>\n
There is overlap between the conditions studied by the Engle Lab and the conditions seen through the CCDD clinic at Boston Children\u2019s Hospital.\u00a0 However, the research and formal medical evaluations are performed through separate programs. People can choose to participate in, and be appropriate for, one or both options.\u00a0 To pre-screen individuals for either program (research enrollment or clinic visit), Dr. Engle and her team review clinical information provided through forms and medical records. This helps us to be sure that the desired study and\/or clinic participation are appropriate.<\/p>\n
Continue reading below to learn more or click on the buttons to move to a specific section.<\/p>\n
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<\/p>\n<\/p>\nEnrolling Into Our Research<\/div>\n <\/div>\n
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<\/p>\n<\/p>\nAttending Ocular CCDD Clinic<\/div>\n <\/div>\n
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<\/p>\n<\/p>\nFrequently Asked Questions (FAQs)<\/div>\n <\/div>\n
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Dr. Elizabeth Engle (center, front) and members of the Engle Lab commemorating Moebius Syndrome Awareness Day 2020.<\/em><\/p>\n[\/et_pb_text][et_pb_text module_id=”genetics” _builder_version=”4.5.3″ max_width=”100%” custom_margin=”|-571px||||”]<\/p>\n
Enrolling in Engle Lab Research Studies<\/h2>\n
The Engle Lab\u2019s research enrollment goals are to (1) enroll participants who are born with complex eye and facial movement disorders or disorders of lower cranial nerve function together with family members and\u00a0 (2) enroll families in which three or more relatives are diagnosed with strabismus.\u00a0 Patients, parents, health care providers and other researchers all refer individuals to us for enrollment.<\/p>\n
Examples of disorders we study:<\/h3>\n\n- Complex congenital eye and eyelid movement disorders:<\/li>\n
\n- Congenital Fibrosis of the Extraocular Muscles (CFEOM)<\/li>\n
- Congenital ptosis<\/li>\n
- Marcus Gunn Jaw Winking syndrome (MGJWS)<\/li>\n
- Duane syndrome \/ Duane retraction syndrome (DRS)<\/li>\n
- Horizontal Gaze Palsy (HGP)<\/li>\n
- Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)<\/li>\n
- Moebius syndrome \/ Moebius sequence (MBS)<\/li>\n
- Congenital 3rd, 4th, or 6th nerve palsy<\/li>\n
- Ocular and lid synkinesis<\/li>\n
- Any other complex congenital eye or lid movement disorder (yet to be defined)<\/li>\n<\/ul>\n
- Congenital facial weakness or palsy<\/li>\n
\n- Isolated congenital facial weakness<\/li>\n
- Syndromic congenital facial weakness<\/li>\n
- Moebius syndrome<\/li>\n<\/ul>\n
- Congenital disorders of lower cranial nerves<\/li>\n
\n- Examples include disorders of tongue movement, chewing, or swallowing<\/li>\n<\/ul>\n
- Familial Strabismus<\/li>\n
\n- Families in which 3 or more relatives are diagnosed with strabismus, including but not limited to esotropia, infantile esotropia, accommodative esotropia, intermittent esotropia, and exotropia.<\/li>\n<\/ul>\n<\/ul>\n
The conditions we study generally cause symptoms that are noted in infancy or early childhood, even if an official diagnosis is not made for several years. If symptoms begin in adulthood or are due to surgery or trauma, our study is unlikely to be appropriate.\u00a0 Please do not hesitate to contact us with questions about eligibility.<\/p>\n
What participation includes:<\/h3>\n\n- All participation steps can be arranged remotely. Travel to Boston is not required.<\/li>\n
- There are no fees nor costs to participate.<\/li>\n
- We can explain the study and enrollment process and answer any questions via telephone, video conferencing, or secure email. If a potential participant is being seen at Boston Children\u2019s Hospital, we may also be able to meet in person.<\/li>\n
- Enrollment is ongoing and rolling with no predetermined end date.<\/li>\n
- Our goal is to enroll all affected and unaffected close members of a family (such as parents and siblings) when feasible.<\/li>\n
- Enrollment consists of four steps: 1) Screening, 2) Consenting, 3) Request for medical records, imaging, and test results, and 4) Sampling.<\/li>\n<\/ul>\n
1. Screening<\/h4>\n
Receiving initial information about potential participants through a screening form allows us to determine if enrollment in our study is appropriate.\u00a0 We gather this information through an Intake Form<\/a>\u00a0that can be downloaded or collected by phone. Once completed, please return the form via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a><\/p>\n2. Consenting<\/h4>\n
Informed consent from each participant is obtained. Informed consent is a legal term. It means that the potential participant is fully aware of the facts and risks of participating in the research study before agreeing to it. An Engle Lab staff member will obtain consent by phone or videoconference. This session provides an opportunity for the potential participant and family to ask questions and for us to be sure that everyone is aware of the study process. For minors or people under guardianship, in addition to consent, we may obtain assent from the participant. For families with appointments at Boston Children\u2019s Hospital, in-person consenting may also be an option.\u00a0 Depending on the discussion and number of questions, the consenting process typically takes 10-20 minutes.\u00a0 Participants are given an opportunity to read the consent carefully prior to the discussion, and forms can be emailed directly and\/or included in an enrollment kit.\u00a0 Once all questions have been satisfactorily addressed and consenting has been completed and is on file, we move on to sampling.<\/p>\n
3. Request for medical records, imaging, and test results<\/h4>\n
In addition to the initial intake form, we require additional clinical information to successfully study an enrolled individual or family.\u00a0 This information can be obtained throughout the enrollment and participation process. We request that the participants fill out the forms below: clinical history form, medical history form, and medical records release form that provide permission for us to request medical records and copies of imaging studies (typically MRI scans). Please note that some facilities require that patients use that facility\u2019s specific release form; information on our form should help you to complete any requests to share records with us. We also ask for photos and videos of eye and facial movements (some of which can be done online). Please download these forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a>\u00a0Links to additional forms including a sample consent are also available in the FAQs below.<\/p>\nWhat forms or information are required?\u00a0<\/em><\/h5>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
4. Sampling<\/h4>\n
The Engle Lab genetic studies typically require a saliva or blood sample from each participant.\u00a0 Once received by the lab, this sample is used to extract DNA. Saliva samples can be obtained in the comfort of the home, using special collection tubes that we can mail, along with some paperwork, directly to you or to your doctor\u2019s office. These samples and paperwork are then returned to the lab using our mailers at our cost.\u00a0 As with the other steps, if you are receiving care at Boston Children\u2019s Hospital, we can arrange to meet with you in person to complete sampling. On rare occasions when the lab cannot successfully obtain adequate DNA from a sample, we may need to request a repeat saliva sample or an alternative sample, such as via a blood draw.\u00a0 On other rare occasions a participant may prefer to provide a blood sample rather than a saliva sample.<\/p>\n
Please do not hesitate to contact us with any questions about the enrollment process.<\/strong><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
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Dr. Elizabeth Engle and Dr. David Hunter.<\/em><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/3.-patient-study-button-scaled.jpg” title_text=”3. patient & study button” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. David Hunter and Sarah Mackinnon (orthoptist) evaluating a patient at the Moebius Syndrome Foundation (MSF) Annual Meeting.<\/em><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.9.7″]<\/p>\n
Attending the Ocular CCDD Clinic<\/h2>\n
Elizabeth Engle<\/a> MD (Neurologist),\u00a0David Hunter<\/a>\u00a0 MD, PhD (Ophthalmologist-in-Chief),\u00a0Sarah MacKinnon<\/a>\u00a0MSc, OC(C), CO, COMT (Chief Orthoptist) and Brenda Barry<\/a>\u00a0MS CGC (Genetic Counselor) hold a combined outpatient clinic in which they evaluate individuals of all ages who have, or may have, an ocular CCDD.<\/p>\nCCDD clinic patients undergo ophthalmological and neurological consultations. Diagnosis, etiologies, prognosis, treatment options, genetic testing, and research enrollment options may be discussed at the clinic visit. Drs. Hunter and Engle will both be present to answer questions and address concerns.<\/p>\n
Appointments generally last 3 to 4 hours and the clinic is typically held the first Monday afternoon of the month in the Ophthalmology Department, Fegan 4, Boston Children\u2019s Hospital main campus, 300 Longwood Avenue, Boston, MA.<\/p>\n
Screening<\/h3>\n
We request information in advance of CCDD clinic visits. This information allows us to be certain that the patient is seen by the correct specialists and allows us to review the patient\u2019s history in advance. If you or a family member or patient wishes to be screened for CCDD clinic, please download and fill out the four forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail<\/a>.<\/p>\n\n- Intake Form<\/a><\/li>\n
- Clinical History Form<\/a><\/span><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
Please contact englegc.research@childrens.harvard.edu<\/a>\u00a0for more information about the CCDD clinic and\/or to schedule an appointment.\u00a0 If an appointment is appropriate, you will be connected with administrative staff at the hospital to obtain a medical records number and to receive help regarding any billing and insurance questions.<\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
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Frequently Asked Questions (FAQs)<\/h2>\nWhat is strabismus?<\/em><\/h4>\nStrabismus refers to eyes that are misaligned.\u00a0 This misalignment, or inability of the eyes to coordinate movements, may be present from infancy or develop over time and is thought to affect 1-5% of the general population.\u00a0 We are still learning about strabismus, but we know it can be caused by problems with the eye muscles, the nerves that control these muscles, or problems with how the brain processes visual information.\u00a0 The Engle Lab studies familial strabismus of all types and complex strabismus syndromes that are present from birth or infancy.<\/p>\n
What is a CCDD?\u00a0<\/em><\/h4>\nCongenital Cranial Dysinnervation Disorders (CCDDs) are neurological conditions affecting one or more of the cranial motor nerves. The cranial motor nerves develop from the brain and connect to muscles and tissues to control functions such as movement of the eyes and eyelids, facial expression, blinking, chewing, and swallowing. CCDDs that impact eye movements, and often cause strabismus, are called ocular CCDDs.\u00a0 Ocular CCDDs include CFEOM (congenital fibrosis of extraocular muscles), Duane syndrome, 3rd, 4th, and 6th nerve palsy, Moebius syndrome, ocular synkinesis syndromes and horizontal gaze palsy with progressive scoliosis (HGPPS). Other CCDDs most prominently affect facial movements, resulting in congenital facial weakness.<\/p>\n
What genes are studied by the Engle Lab?<\/em><\/h4>\nThe Engle Lab has identified, characterized, and continues to study multiple genetic disorders that alter the development and function of the nerves and muscles critical for typical eye and facial movements.\u00a0 Some of the molecules and pathways we study are related to mutations in the following genes: KIF21A, TUBB3, TUBB2B, <\/em>and PHOX2A<\/em> that cause CFEOM; \u00a0CHN1, MAFB, HOXA1,<\/em> SALL4, <\/em>and ROBO3\u00a0 <\/em>that cause Duane syndrome \/ horizontal gaze palsy; and HOXB1 <\/em>that causes congenital facial weakness.<\/p>\nThe Engle Lab is also focused on identifying new, previously uncharacterized genetic causes of CCDDs.\u00a0 For this reason, our set-up and methods differ from those of commercial testing labs that exist to precisely test known genes.\u00a0 If your health care provider feels that a known genetic condition may explain the symptoms you or a family member are experiencing, genetic testing for that condition may now be commercially available because of past research successes.\u00a0 If so, it may be more efficient to directly pursue that testing in a clinical lab rather than enrolling in a research study that has an uncertain timeline for results and the need for repeated sampling and confirmation testing.<\/p>\n
Is there a cost to participants?<\/em><\/h4>\nThere is no cost to participate and travel is not required. There is also no compensation for participation in our study.<\/p>\n
What are the goals of the study?<\/em><\/h4>\nWe use DNA from participants to identify and study new genetic causes of CCDDs and impaired eye and facial movements. The clinical information helps us to understand what a gene does normally and what can result if it is mutated and thus not working normally. From a clinical standpoint, by understanding the genetic cause of a given CCDD we hope to improve diagnosis and treatment, and to provide accurate genetic counseling.<\/p>\n
What is the enrollment process?<\/em><\/h4>\nWe welcome contact by email, phone, or postal mail<\/a> from patients, parents, and healthcare providers to determine if someone is eligible for the study.\u00a0 Once we receive an inquiry and screening forms, research staff contact you to discuss enrollment or request additional information, review the consent form, and guide the sampling process.<\/p>\nWhat type of medical information is helpful?<\/em><\/h4>\nWe benefit from collecting details through interviews and forms completed by patients themselves or their health care providers, as well as through receipt of primary medical records.\u00a0 Typically, of greatest help are records related to ophthalmology, neurology, and genetics, including exam and surgical notes, testing results, and copies of brain\/eye imaging (especially MRI scans). We can also provide a link to an online web app, StrabisPIX<\/a>, developed by our colleagues in Ophthalmology at Boston Children\u2019s Hospital to capture photographs of eye positions.<\/p>\nWhat types of samples are needed for participation?<\/em><\/h4>\nWe generally start by obtaining DNA using a specialized saliva collection kit that we provide to families.\u00a0 Sometimes we may ask for a blood draw if collection of DNA using saliva is not successful or if we have a specific need for whole blood.\u00a0 We may also obtain already stored DNA and\/or tissue that may have been collected through a doctor\u2019s office and is no longer needed.\u00a0 Most commonly, only one sample is required.\u00a0 However, if the DNA is of poor quality, is used up over the course of the research, or we have a specialized project, we may reach out to enrolled participants to request additional samples, if they have provided consent for us to recontact them.<\/p>\n
Who can participate?<\/em><\/h4>\nWe need to enroll and obtain DNA from at least one family member diagnosed with a condition we study.\u00a0 If only one person in the family has the condition, we would likely request that the person\u2019s parents and siblings also enroll. If more than one person in the family has the condition, we would likely ask if all affected individuals and their immediate family members would enroll.\u00a0 This allows us to compare changes we find in the DNA of the persons with the diagnosis to the DNA of unaffected family members to best interpret genetic findings.\u00a0 However, we acknowledge that enrolling additional biological relatives is not always feasible. Importantly, we must consent each participant and receive their sample.<\/p>\n
What forms or information are required?\u00a0<\/em><\/h4>\nWe ask to receive back a general intake and 3 initial forms from people interested in the study. Other materials, including the consent and submission form, are provided by email and\/or with the enrollment kit. These forms may be downloaded by clicking below.\u00a0 They can be completed and returned by email<\/a> or regular mail<\/a>.<\/p>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n
- Example Consent (this is an example and should not be used for enrollment)<\/span><\/a><\/li>\n
- Sample Submission Form<\/span><\/a><\/li>\n
- Participant Questionnaire (PQ)<\/span><\/a><\/li>\n<\/ul>\n
Are study participation and results confidential?<\/em><\/h4>\nOur lab collects DNA samples and medical information from persons and families with features indicating they have or may have a CCDD or familial strabismus.\u00a0 The information is kept confidential.\u00a0 Identifiable details are not shared with anyone outside of the Engle Lab without the specific permission of participants.\u00a0 No results are placed in the medical record of participating individuals or their families prior to clinical confirmation. We consent people to make sure everyone understands important details of the study and how we protect participant data.<\/p>\n
Can participants obtain results?<\/em><\/h4>\nAnalyses will be done in our research laboratory and so are considered investigational. This means that we cannot directly release results to a participant. However, participants can call or email us at any time to ask questions or to check in on the overall progress of the program. In addition, participants are given choices on the consent form to indicate if s\/he wishes to be informed about the availability of results. If we identify findings for a specific participant who has noted s\/he wished to be informed of significant results, we would attempt to contact the participant and\/or a designated medical provider (based on information obtained during enrollment or as updated by the participant).\u00a0 We would work with them to have our research findings confirmed by an authorized clinical laboratory which would then issue a report that would become part of the medical record and provide details about the results.\u00a0Our research findings are also shared through scientific publications. The results in such publications do not include any information that would permit identification of participants. We can provide copies of these publications on request.<\/p>\n
What are possible benefits of participation?<\/em><\/h4>\nEach and every participant contributes to the improved understanding of the CCDDs.\u00a0 Some participants may also learn about the genetic basis of their condition.<\/p>\n
How can I tell other people about this study?<\/em><\/h4>\nYou may tell people about this website and share all of our contact information with anyone you wish. You may also download and share\u00a0these pamphlets\u00a0about the research on cranial nerves<\/a> and on facial weakness and Moebius syndrome.<\/a><\/span><\/p>\n<\/em><\/h4>\n<\/em><\/h4>\nWhat other resources exist?<\/em><\/h4>\n\n- Adult Strabismus Q&A with Dr. Hunter<\/a><\/li>\n
- Clinical Trials<\/a><\/li>\n
- Boston Children\u2019s Hospital Clinical Trials<\/a><\/li>\n
- GeneReviews CFEOM<\/a><\/li>\n
- GeneReviews Duane Syndrome<\/a><\/li>\n
- Moebius Syndrome Foundation<\/a><\/li>\n<\/ul>\n
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The Engle Lab at the F.M. Kirby Neurobiology Center Patient & Study Participant ResourcesWelcome, we are glad you found us!\u00a0 You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information […]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\n
[et_pb_section fb_built=\"1\" admin_label=\"BKGD IMAGE\" _builder_version=\"4.5.0\" background_color=\"#000000\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" background_enable_image=\"off\" background_size=\"initial\" custom_padding=\"1px|0px|0|0px|false|false\" global_module=\"3860\" saved_tabs=\"all\"][et_pb_row _builder_version=\"4.5.0\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" min_height=\"353px\" custom_margin=\"|auto||161px||\" custom_padding=\"17px|0px|255px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"home_header\" _builder_version=\"4.5.0\" text_font=\"||||||||\" header_font=\"||||||||\" min_height=\"39px\" custom_css_main_element=\"color:#ffffff;||line-height:0.95em;||font-family:el messiri;||font-size:44px;||font-weight:normal;\" inline_fonts=\"Merriweather,El Messiri,Georgia\"]<\/div>\n<\/div>\nThe Engle Lab<\/div>\nat the FM Kirby Neurobiology Center<\/div>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"4.4.5\" background_color=\"#ffffff\" custom_padding=\"0|0px|0|0px|false|false\"][et_pb_row _builder_version=\"4.3.4\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text _builder_version=\"4.4.5\"]<\/span><\/p>\nScience & Research<\/span><\/p>[\/et_pb_text][et_pb_text _builder_version=\"4.4.5\"]For a full list of Engle Lab publications, please click here<\/a>. To request a PDF of a lab publication, email engle.admin@childrens.harvard.edu<\/a>.<\/p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"3.22.3\" custom_padding=\"0|0px|47.625px|0|false|false\"][et_pb_row column_structure=\"1_3,1_3,1_3\" _builder_version=\"4.5.0\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"1_3\" _builder_version=\"4.5.0\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#CCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" background_enable_color=\"off\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#Transcriptomics\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Transcriptomic and Epigenomic Analyses of the Developing Brainstem<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsCCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Disease Modeling<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsEsotropiaExotropia\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of Esotropia & Exotropia<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Imaging<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=\"topic-two\" _builder_version=\"3.25\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_divider _builder_version=\"3.23.4\" height=\"0px\"][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=\"1_2,1_2\" module_id=\"CCDDs\" _builder_version=\"4.5.0\" custom_padding=\"30px|0px|25.2344px|0px|false|false\" link_option_url=\"#CCDDs\"][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_image src=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/CCDD-image.001-2.jpeg\" title_text=\"CCDD image.001\" align_tablet=\"center\" align_phone=\"\" align_last_edited=\"on|desktop\" _builder_version=\"4.5.0\"][\/et_pb_image][et_pb_text _builder_version=\"3.27.4\" text_font=\"||||||||\" text_font_size=\"1px\" custom_margin=\"-20px||\" custom_padding=\"0px||\"]Optional image caption and attribution<\/em><\/p>[\/et_pb_text][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]Publications<\/h3>\n
Publication 1 ><\/p>\n
Publication 2 ><\/p>[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]
Congenital Cranial Dysinnervation Disorders (CCDDs)<\/h2>\n
We humans are defined, in part, by the nuanced and coordinated ocular and facial movements that are fundamental to our vision and social communication. The Engle Lab studies human developmental disorders that perturb these eye and face movements as a framework to understand how neurons are specified and how cranial neural circuits are formed. We identify human disorders of eye and face movement, define their genetic etiologies, and study the developmental pathology and disease mechanism in vitro and in animal models. We also study the normal development of cranial motor neurons and their axonal processes. Our research has led to the definition of the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are birth defects in which cranial motor neurons or their axonal processes fail to develop correctly. While the CCDDs include all cranial motor nerves, the lab focuses in particular on disorders of oculomotor (cranial nerve 3), trochlear (cranial nerve 4), abducens (cranial nerve 6) and\/or facial (cranial nerve 7) development. The ocular CCDDs result in the inability to raise the eyelid(s) or to move the eye(s) in one or more directions of gaze. The facial CCDDs result in unilateral or bilateral h bvdsafacial weakness. We also study the genetics of esotropia and exotropia (common or comitant forms of strabismus), as described below<\/a>.<\/span><\/p>\nThe lab has found that human disorders of cranial motor neuron development provide a unique and powerful system to study Mendelian genetics and neural connectivity:<\/span><\/p>\n\n- Each cranial motor nucleus contains a small number of motor neurons.<\/span><\/li>\n
- Each cranial motor nerve has straightforward tractable developmental anatomy that can be visualized in three dimensions.<\/span><\/li>\n
- Errors in development result in human phenotypes that are present at birth, lifelong, visible to the examiner, and stereotypic in presentation.<\/span><\/li>\n
- All higher vertebrates have 12 highly conserved cranial nerves, providing consistent translation to model organisms for developmental and mechanistic studies.<\/span><\/li>\n
- The Engle Lab has amassed a remarkable Mendelian cohort of research participants, leading to a high likelihood that we will identify multiple disease alleles with which to document causality of a new genetic disorder.<\/span><\/li>\n<\/ul>[\/et_pb_text][et_pb_text _builder_version=\"3.27.4\"]
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<\/span><\/p>\nPatient & Study Participant Resources<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.5.3″ custom_padding=”0|0px|47.625px|0|false|false”][et_pb_row _builder_version=”4.5.0″ _module_preset=”default” custom_padding=”||0px|||”][et_pb_column type=”4_4″ _builder_version=”4.5.0″ _module_preset=”default”][et_pb_text _builder_version=”4.5.3″ _module_preset=”default”]<\/p>\n
Welcome, we are glad you found us!\u00a0<\/strong><\/h2>\nYou may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information will address questions you may have about enrolling in our research and\/or attending our CCDD Consultation Clinic.<\/p>\n
From a research standpoint, the Engle Lab strives to better understand the neurogenetic basis of cranial nerve development and function.\u00a0 This is done through gene discovery and basic research described in the Science section<\/a> of our website. Gene discovery requires the enrollment and participation of individuals and families diagnosed with rare conditions involving atypical or limited eye and facial movements. These conditions include both defined or undefined congenital cranial dysinnervation disorders (CCDDs)<\/a>\u00a0and familial strabismus<\/a>.<\/p>\nDr. Engle and her colleagues also oversee and participate in a multi-disciplinary, second-opinion consultation clinic at Boston Children\u2019s Hospital for children and adults diagnosed with ocular CCDDs. This clinic is staffed by two physicians, Dr. Elizabeth Engle, a child neurologist and pediatrician, and Dr. David Hunter, an ophthalmologist, as well as an\u00a0orthoptist <\/a>and genetic counselor<\/a>.\u00a0More information on this clinic is provided in\u00a0\u00a0“Attending the Ocular CCDD Clinic”<\/a>.<\/p>\n\n- See our FAQs section<\/a> for definitions and additional background.<\/li>\n<\/ul>\n
How can I participate or become involved?<\/h2>\n
There is overlap between the conditions studied by the Engle Lab and the conditions seen through the CCDD clinic at Boston Children\u2019s Hospital.\u00a0 However, the research and formal medical evaluations are performed through separate programs. People can choose to participate in, and be appropriate for, one or both options.\u00a0 To pre-screen individuals for either program (research enrollment or clinic visit), Dr. Engle and her team review clinical information provided through forms and medical records. This helps us to be sure that the desired study and\/or clinic participation are appropriate.<\/p>\n
Continue reading below to learn more or click on the buttons to move to a specific section.<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.9.7″ custom_margin=”0px|auto|0px|auto|false|false” custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_3″ _builder_version=”4.5.0″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#CCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ background_enable_color=”off” max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
<\/p>\n<\/p>\nEnrolling Into Our Research<\/div>\n <\/div>\n
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[\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsCCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
<\/p>\n<\/p>\nAttending Ocular CCDD Clinic<\/div>\n <\/div>\n
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[\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsEsotropiaExotropia” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n
<\/p>\n<\/p>\nFrequently Asked Questions (FAQs)<\/div>\n <\/div>\n
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[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”Enrolling” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” link_option_url=”#CCDDs” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/08\/new.MBS_.lab_.jpg” title_text=”new.MBS.lab” align=”center” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″ width=”57%” module_alignment=”center” height=”362px”][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” width=”100%” custom_margin=”-20px||” custom_padding=”0px|||217px|false|false”]<\/p>\n
Dr. Elizabeth Engle (center, front) and members of the Engle Lab commemorating Moebius Syndrome Awareness Day 2020.<\/em><\/p>\n[\/et_pb_text][et_pb_text module_id=”genetics” _builder_version=”4.5.3″ max_width=”100%” custom_margin=”|-571px||||”]<\/p>\n
Enrolling in Engle Lab Research Studies<\/h2>\n
The Engle Lab\u2019s research enrollment goals are to (1) enroll participants who are born with complex eye and facial movement disorders or disorders of lower cranial nerve function together with family members and\u00a0 (2) enroll families in which three or more relatives are diagnosed with strabismus.\u00a0 Patients, parents, health care providers and other researchers all refer individuals to us for enrollment.<\/p>\n
Examples of disorders we study:<\/h3>\n\n- Complex congenital eye and eyelid movement disorders:<\/li>\n
\n- Congenital Fibrosis of the Extraocular Muscles (CFEOM)<\/li>\n
- Congenital ptosis<\/li>\n
- Marcus Gunn Jaw Winking syndrome (MGJWS)<\/li>\n
- Duane syndrome \/ Duane retraction syndrome (DRS)<\/li>\n
- Horizontal Gaze Palsy (HGP)<\/li>\n
- Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)<\/li>\n
- Moebius syndrome \/ Moebius sequence (MBS)<\/li>\n
- Congenital 3rd, 4th, or 6th nerve palsy<\/li>\n
- Ocular and lid synkinesis<\/li>\n
- Any other complex congenital eye or lid movement disorder (yet to be defined)<\/li>\n<\/ul>\n
- Congenital facial weakness or palsy<\/li>\n
\n- Isolated congenital facial weakness<\/li>\n
- Syndromic congenital facial weakness<\/li>\n
- Moebius syndrome<\/li>\n<\/ul>\n
- Congenital disorders of lower cranial nerves<\/li>\n
\n- Examples include disorders of tongue movement, chewing, or swallowing<\/li>\n<\/ul>\n
- Familial Strabismus<\/li>\n
\n- Families in which 3 or more relatives are diagnosed with strabismus, including but not limited to esotropia, infantile esotropia, accommodative esotropia, intermittent esotropia, and exotropia.<\/li>\n<\/ul>\n<\/ul>\n
The conditions we study generally cause symptoms that are noted in infancy or early childhood, even if an official diagnosis is not made for several years. If symptoms begin in adulthood or are due to surgery or trauma, our study is unlikely to be appropriate.\u00a0 Please do not hesitate to contact us with questions about eligibility.<\/p>\n
What participation includes:<\/h3>\n\n- All participation steps can be arranged remotely. Travel to Boston is not required.<\/li>\n
- There are no fees nor costs to participate.<\/li>\n
- We can explain the study and enrollment process and answer any questions via telephone, video conferencing, or secure email. If a potential participant is being seen at Boston Children\u2019s Hospital, we may also be able to meet in person.<\/li>\n
- Enrollment is ongoing and rolling with no predetermined end date.<\/li>\n
- Our goal is to enroll all affected and unaffected close members of a family (such as parents and siblings) when feasible.<\/li>\n
- Enrollment consists of four steps: 1) Screening, 2) Consenting, 3) Request for medical records, imaging, and test results, and 4) Sampling.<\/li>\n<\/ul>\n
1. Screening<\/h4>\n
Receiving initial information about potential participants through a screening form allows us to determine if enrollment in our study is appropriate.\u00a0 We gather this information through an Intake Form<\/a>\u00a0that can be downloaded or collected by phone. Once completed, please return the form via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a><\/p>\n2. Consenting<\/h4>\n
Informed consent from each participant is obtained. Informed consent is a legal term. It means that the potential participant is fully aware of the facts and risks of participating in the research study before agreeing to it. An Engle Lab staff member will obtain consent by phone or videoconference. This session provides an opportunity for the potential participant and family to ask questions and for us to be sure that everyone is aware of the study process. For minors or people under guardianship, in addition to consent, we may obtain assent from the participant. For families with appointments at Boston Children\u2019s Hospital, in-person consenting may also be an option.\u00a0 Depending on the discussion and number of questions, the consenting process typically takes 10-20 minutes.\u00a0 Participants are given an opportunity to read the consent carefully prior to the discussion, and forms can be emailed directly and\/or included in an enrollment kit.\u00a0 Once all questions have been satisfactorily addressed and consenting has been completed and is on file, we move on to sampling.<\/p>\n
3. Request for medical records, imaging, and test results<\/h4>\n
In addition to the initial intake form, we require additional clinical information to successfully study an enrolled individual or family.\u00a0 This information can be obtained throughout the enrollment and participation process. We request that the participants fill out the forms below: clinical history form, medical history form, and medical records release form that provide permission for us to request medical records and copies of imaging studies (typically MRI scans). Please note that some facilities require that patients use that facility\u2019s specific release form; information on our form should help you to complete any requests to share records with us. We also ask for photos and videos of eye and facial movements (some of which can be done online). Please download these forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a>\u00a0Links to additional forms including a sample consent are also available in the FAQs below.<\/p>\nWhat forms or information are required?\u00a0<\/em><\/h5>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
4. Sampling<\/h4>\n
The Engle Lab genetic studies typically require a saliva or blood sample from each participant.\u00a0 Once received by the lab, this sample is used to extract DNA. Saliva samples can be obtained in the comfort of the home, using special collection tubes that we can mail, along with some paperwork, directly to you or to your doctor\u2019s office. These samples and paperwork are then returned to the lab using our mailers at our cost.\u00a0 As with the other steps, if you are receiving care at Boston Children\u2019s Hospital, we can arrange to meet with you in person to complete sampling. On rare occasions when the lab cannot successfully obtain adequate DNA from a sample, we may need to request a repeat saliva sample or an alternative sample, such as via a blood draw.\u00a0 On other rare occasions a participant may prefer to provide a blood sample rather than a saliva sample.<\/p>\n
Please do not hesitate to contact us with any questions about the enrollment process.<\/strong><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
BACK TO TOP ^<\/a><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ module_id=”CCDDClinic” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/2012_Chair-celebration_Engle-Hunter.jpg” title_text=”2012_Chair celebration_Engle-Hunter” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. Elizabeth Engle and Dr. David Hunter.<\/em><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/3.-patient-study-button-scaled.jpg” title_text=”3. patient & study button” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. David Hunter and Sarah Mackinnon (orthoptist) evaluating a patient at the Moebius Syndrome Foundation (MSF) Annual Meeting.<\/em><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.9.7″]<\/p>\n
Attending the Ocular CCDD Clinic<\/h2>\n
Elizabeth Engle<\/a> MD (Neurologist),\u00a0David Hunter<\/a>\u00a0 MD, PhD (Ophthalmologist-in-Chief),\u00a0Sarah MacKinnon<\/a>\u00a0MSc, OC(C), CO, COMT (Chief Orthoptist) and Brenda Barry<\/a>\u00a0MS CGC (Genetic Counselor) hold a combined outpatient clinic in which they evaluate individuals of all ages who have, or may have, an ocular CCDD.<\/p>\nCCDD clinic patients undergo ophthalmological and neurological consultations. Diagnosis, etiologies, prognosis, treatment options, genetic testing, and research enrollment options may be discussed at the clinic visit. Drs. Hunter and Engle will both be present to answer questions and address concerns.<\/p>\n
Appointments generally last 3 to 4 hours and the clinic is typically held the first Monday afternoon of the month in the Ophthalmology Department, Fegan 4, Boston Children\u2019s Hospital main campus, 300 Longwood Avenue, Boston, MA.<\/p>\n
Screening<\/h3>\n
We request information in advance of CCDD clinic visits. This information allows us to be certain that the patient is seen by the correct specialists and allows us to review the patient\u2019s history in advance. If you or a family member or patient wishes to be screened for CCDD clinic, please download and fill out the four forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail<\/a>.<\/p>\n\n- Intake Form<\/a><\/li>\n
- Clinical History Form<\/a><\/span><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
Please contact englegc.research@childrens.harvard.edu<\/a>\u00a0for more information about the CCDD clinic and\/or to schedule an appointment.\u00a0 If an appointment is appropriate, you will be connected with administrative staff at the hospital to obtain a medical records number and to receive help regarding any billing and insurance questions.<\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
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Frequently Asked Questions (FAQs)<\/h2>\nWhat is strabismus?<\/em><\/h4>\nStrabismus refers to eyes that are misaligned.\u00a0 This misalignment, or inability of the eyes to coordinate movements, may be present from infancy or develop over time and is thought to affect 1-5% of the general population.\u00a0 We are still learning about strabismus, but we know it can be caused by problems with the eye muscles, the nerves that control these muscles, or problems with how the brain processes visual information.\u00a0 The Engle Lab studies familial strabismus of all types and complex strabismus syndromes that are present from birth or infancy.<\/p>\n
What is a CCDD?\u00a0<\/em><\/h4>\nCongenital Cranial Dysinnervation Disorders (CCDDs) are neurological conditions affecting one or more of the cranial motor nerves. The cranial motor nerves develop from the brain and connect to muscles and tissues to control functions such as movement of the eyes and eyelids, facial expression, blinking, chewing, and swallowing. CCDDs that impact eye movements, and often cause strabismus, are called ocular CCDDs.\u00a0 Ocular CCDDs include CFEOM (congenital fibrosis of extraocular muscles), Duane syndrome, 3rd, 4th, and 6th nerve palsy, Moebius syndrome, ocular synkinesis syndromes and horizontal gaze palsy with progressive scoliosis (HGPPS). Other CCDDs most prominently affect facial movements, resulting in congenital facial weakness.<\/p>\n
What genes are studied by the Engle Lab?<\/em><\/h4>\nThe Engle Lab has identified, characterized, and continues to study multiple genetic disorders that alter the development and function of the nerves and muscles critical for typical eye and facial movements.\u00a0 Some of the molecules and pathways we study are related to mutations in the following genes: KIF21A, TUBB3, TUBB2B, <\/em>and PHOX2A<\/em> that cause CFEOM; \u00a0CHN1, MAFB, HOXA1,<\/em> SALL4, <\/em>and ROBO3\u00a0 <\/em>that cause Duane syndrome \/ horizontal gaze palsy; and HOXB1 <\/em>that causes congenital facial weakness.<\/p>\nThe Engle Lab is also focused on identifying new, previously uncharacterized genetic causes of CCDDs.\u00a0 For this reason, our set-up and methods differ from those of commercial testing labs that exist to precisely test known genes.\u00a0 If your health care provider feels that a known genetic condition may explain the symptoms you or a family member are experiencing, genetic testing for that condition may now be commercially available because of past research successes.\u00a0 If so, it may be more efficient to directly pursue that testing in a clinical lab rather than enrolling in a research study that has an uncertain timeline for results and the need for repeated sampling and confirmation testing.<\/p>\n
Is there a cost to participants?<\/em><\/h4>\nThere is no cost to participate and travel is not required. There is also no compensation for participation in our study.<\/p>\n
What are the goals of the study?<\/em><\/h4>\nWe use DNA from participants to identify and study new genetic causes of CCDDs and impaired eye and facial movements. The clinical information helps us to understand what a gene does normally and what can result if it is mutated and thus not working normally. From a clinical standpoint, by understanding the genetic cause of a given CCDD we hope to improve diagnosis and treatment, and to provide accurate genetic counseling.<\/p>\n
What is the enrollment process?<\/em><\/h4>\nWe welcome contact by email, phone, or postal mail<\/a> from patients, parents, and healthcare providers to determine if someone is eligible for the study.\u00a0 Once we receive an inquiry and screening forms, research staff contact you to discuss enrollment or request additional information, review the consent form, and guide the sampling process.<\/p>\nWhat type of medical information is helpful?<\/em><\/h4>\nWe benefit from collecting details through interviews and forms completed by patients themselves or their health care providers, as well as through receipt of primary medical records.\u00a0 Typically, of greatest help are records related to ophthalmology, neurology, and genetics, including exam and surgical notes, testing results, and copies of brain\/eye imaging (especially MRI scans). We can also provide a link to an online web app, StrabisPIX<\/a>, developed by our colleagues in Ophthalmology at Boston Children\u2019s Hospital to capture photographs of eye positions.<\/p>\nWhat types of samples are needed for participation?<\/em><\/h4>\nWe generally start by obtaining DNA using a specialized saliva collection kit that we provide to families.\u00a0 Sometimes we may ask for a blood draw if collection of DNA using saliva is not successful or if we have a specific need for whole blood.\u00a0 We may also obtain already stored DNA and\/or tissue that may have been collected through a doctor\u2019s office and is no longer needed.\u00a0 Most commonly, only one sample is required.\u00a0 However, if the DNA is of poor quality, is used up over the course of the research, or we have a specialized project, we may reach out to enrolled participants to request additional samples, if they have provided consent for us to recontact them.<\/p>\n
Who can participate?<\/em><\/h4>\nWe need to enroll and obtain DNA from at least one family member diagnosed with a condition we study.\u00a0 If only one person in the family has the condition, we would likely request that the person\u2019s parents and siblings also enroll. If more than one person in the family has the condition, we would likely ask if all affected individuals and their immediate family members would enroll.\u00a0 This allows us to compare changes we find in the DNA of the persons with the diagnosis to the DNA of unaffected family members to best interpret genetic findings.\u00a0 However, we acknowledge that enrolling additional biological relatives is not always feasible. Importantly, we must consent each participant and receive their sample.<\/p>\n
What forms or information are required?\u00a0<\/em><\/h4>\nWe ask to receive back a general intake and 3 initial forms from people interested in the study. Other materials, including the consent and submission form, are provided by email and\/or with the enrollment kit. These forms may be downloaded by clicking below.\u00a0 They can be completed and returned by email<\/a> or regular mail<\/a>.<\/p>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n
- Example Consent (this is an example and should not be used for enrollment)<\/span><\/a><\/li>\n
- Sample Submission Form<\/span><\/a><\/li>\n
- Participant Questionnaire (PQ)<\/span><\/a><\/li>\n<\/ul>\n
Are study participation and results confidential?<\/em><\/h4>\nOur lab collects DNA samples and medical information from persons and families with features indicating they have or may have a CCDD or familial strabismus.\u00a0 The information is kept confidential.\u00a0 Identifiable details are not shared with anyone outside of the Engle Lab without the specific permission of participants.\u00a0 No results are placed in the medical record of participating individuals or their families prior to clinical confirmation. We consent people to make sure everyone understands important details of the study and how we protect participant data.<\/p>\n
Can participants obtain results?<\/em><\/h4>\nAnalyses will be done in our research laboratory and so are considered investigational. This means that we cannot directly release results to a participant. However, participants can call or email us at any time to ask questions or to check in on the overall progress of the program. In addition, participants are given choices on the consent form to indicate if s\/he wishes to be informed about the availability of results. If we identify findings for a specific participant who has noted s\/he wished to be informed of significant results, we would attempt to contact the participant and\/or a designated medical provider (based on information obtained during enrollment or as updated by the participant).\u00a0 We would work with them to have our research findings confirmed by an authorized clinical laboratory which would then issue a report that would become part of the medical record and provide details about the results.\u00a0Our research findings are also shared through scientific publications. The results in such publications do not include any information that would permit identification of participants. We can provide copies of these publications on request.<\/p>\n
What are possible benefits of participation?<\/em><\/h4>\nEach and every participant contributes to the improved understanding of the CCDDs.\u00a0 Some participants may also learn about the genetic basis of their condition.<\/p>\n
How can I tell other people about this study?<\/em><\/h4>\nYou may tell people about this website and share all of our contact information with anyone you wish. You may also download and share\u00a0these pamphlets\u00a0about the research on cranial nerves<\/a> and on facial weakness and Moebius syndrome.<\/a><\/span><\/p>\n<\/em><\/h4>\n<\/em><\/h4>\nWhat other resources exist?<\/em><\/h4>\n\n- Adult Strabismus Q&A with Dr. Hunter<\/a><\/li>\n
- Clinical Trials<\/a><\/li>\n
- Boston Children\u2019s Hospital Clinical Trials<\/a><\/li>\n
- GeneReviews CFEOM<\/a><\/li>\n
- GeneReviews Duane Syndrome<\/a><\/li>\n
- Moebius Syndrome Foundation<\/a><\/li>\n<\/ul>\n
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The Engle Lab at the F.M. Kirby Neurobiology Center Patient & Study Participant ResourcesWelcome, we are glad you found us!\u00a0 You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information […]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\n
[et_pb_section fb_built=\"1\" admin_label=\"BKGD IMAGE\" _builder_version=\"4.5.0\" background_color=\"#000000\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" background_enable_image=\"off\" background_size=\"initial\" custom_padding=\"1px|0px|0|0px|false|false\" global_module=\"3860\" saved_tabs=\"all\"][et_pb_row _builder_version=\"4.5.0\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" min_height=\"353px\" custom_margin=\"|auto||161px||\" custom_padding=\"17px|0px|255px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"home_header\" _builder_version=\"4.5.0\" text_font=\"||||||||\" header_font=\"||||||||\" min_height=\"39px\" custom_css_main_element=\"color:#ffffff;||line-height:0.95em;||font-family:el messiri;||font-size:44px;||font-weight:normal;\" inline_fonts=\"Merriweather,El Messiri,Georgia\"]<\/div>\n<\/div>\nThe Engle Lab<\/div>\nat the FM Kirby Neurobiology Center<\/div>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"4.4.5\" background_color=\"#ffffff\" custom_padding=\"0|0px|0|0px|false|false\"][et_pb_row _builder_version=\"4.3.4\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text _builder_version=\"4.4.5\"]<\/span><\/p>\nScience & Research<\/span><\/p>[\/et_pb_text][et_pb_text _builder_version=\"4.4.5\"]For a full list of Engle Lab publications, please click here<\/a>. To request a PDF of a lab publication, email engle.admin@childrens.harvard.edu<\/a>.<\/p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"3.22.3\" custom_padding=\"0|0px|47.625px|0|false|false\"][et_pb_row column_structure=\"1_3,1_3,1_3\" _builder_version=\"4.5.0\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"1_3\" _builder_version=\"4.5.0\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#CCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" background_enable_color=\"off\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#Transcriptomics\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Transcriptomic and Epigenomic Analyses of the Developing Brainstem<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsCCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Disease Modeling<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsEsotropiaExotropia\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of Esotropia & Exotropia<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Imaging<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=\"topic-two\" _builder_version=\"3.25\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_divider _builder_version=\"3.23.4\" height=\"0px\"][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=\"1_2,1_2\" module_id=\"CCDDs\" _builder_version=\"4.5.0\" custom_padding=\"30px|0px|25.2344px|0px|false|false\" link_option_url=\"#CCDDs\"][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_image src=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/CCDD-image.001-2.jpeg\" title_text=\"CCDD image.001\" align_tablet=\"center\" align_phone=\"\" align_last_edited=\"on|desktop\" _builder_version=\"4.5.0\"][\/et_pb_image][et_pb_text _builder_version=\"3.27.4\" text_font=\"||||||||\" text_font_size=\"1px\" custom_margin=\"-20px||\" custom_padding=\"0px||\"]Optional image caption and attribution<\/em><\/p>[\/et_pb_text][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]Publications<\/h3>\n
Publication 1 ><\/p>\n
Publication 2 ><\/p>[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]
Congenital Cranial Dysinnervation Disorders (CCDDs)<\/h2>\n
We humans are defined, in part, by the nuanced and coordinated ocular and facial movements that are fundamental to our vision and social communication. The Engle Lab studies human developmental disorders that perturb these eye and face movements as a framework to understand how neurons are specified and how cranial neural circuits are formed. We identify human disorders of eye and face movement, define their genetic etiologies, and study the developmental pathology and disease mechanism in vitro and in animal models. We also study the normal development of cranial motor neurons and their axonal processes. Our research has led to the definition of the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are birth defects in which cranial motor neurons or their axonal processes fail to develop correctly. While the CCDDs include all cranial motor nerves, the lab focuses in particular on disorders of oculomotor (cranial nerve 3), trochlear (cranial nerve 4), abducens (cranial nerve 6) and\/or facial (cranial nerve 7) development. The ocular CCDDs result in the inability to raise the eyelid(s) or to move the eye(s) in one or more directions of gaze. The facial CCDDs result in unilateral or bilateral h bvdsafacial weakness. We also study the genetics of esotropia and exotropia (common or comitant forms of strabismus), as described below<\/a>.<\/span><\/p>\nThe lab has found that human disorders of cranial motor neuron development provide a unique and powerful system to study Mendelian genetics and neural connectivity:<\/span><\/p>\n\n- Each cranial motor nucleus contains a small number of motor neurons.<\/span><\/li>\n
- Each cranial motor nerve has straightforward tractable developmental anatomy that can be visualized in three dimensions.<\/span><\/li>\n
- Errors in development result in human phenotypes that are present at birth, lifelong, visible to the examiner, and stereotypic in presentation.<\/span><\/li>\n
- All higher vertebrates have 12 highly conserved cranial nerves, providing consistent translation to model organisms for developmental and mechanistic studies.<\/span><\/li>\n
- The Engle Lab has amassed a remarkable Mendelian cohort of research participants, leading to a high likelihood that we will identify multiple disease alleles with which to document causality of a new genetic disorder.<\/span><\/li>\n<\/ul>[\/et_pb_text][et_pb_text _builder_version=\"3.27.4\"]
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<\/span><\/p>\nPatient & Study Participant Resources<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.5.3″ custom_padding=”0|0px|47.625px|0|false|false”][et_pb_row _builder_version=”4.5.0″ _module_preset=”default” custom_padding=”||0px|||”][et_pb_column type=”4_4″ _builder_version=”4.5.0″ _module_preset=”default”][et_pb_text _builder_version=”4.5.3″ _module_preset=”default”]<\/p>\n
Welcome, we are glad you found us!\u00a0<\/strong><\/h2>\nYou may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information will address questions you may have about enrolling in our research and\/or attending our CCDD Consultation Clinic.<\/p>\n
From a research standpoint, the Engle Lab strives to better understand the neurogenetic basis of cranial nerve development and function.\u00a0 This is done through gene discovery and basic research described in the Science section<\/a> of our website. Gene discovery requires the enrollment and participation of individuals and families diagnosed with rare conditions involving atypical or limited eye and facial movements. These conditions include both defined or undefined congenital cranial dysinnervation disorders (CCDDs)<\/a>\u00a0and familial strabismus<\/a>.<\/p>\nDr. Engle and her colleagues also oversee and participate in a multi-disciplinary, second-opinion consultation clinic at Boston Children\u2019s Hospital for children and adults diagnosed with ocular CCDDs. This clinic is staffed by two physicians, Dr. Elizabeth Engle, a child neurologist and pediatrician, and Dr. David Hunter, an ophthalmologist, as well as an\u00a0orthoptist <\/a>and genetic counselor<\/a>.\u00a0More information on this clinic is provided in\u00a0\u00a0“Attending the Ocular CCDD Clinic”<\/a>.<\/p>\n\n- See our FAQs section<\/a> for definitions and additional background.<\/li>\n<\/ul>\n
How can I participate or become involved?<\/h2>\n
There is overlap between the conditions studied by the Engle Lab and the conditions seen through the CCDD clinic at Boston Children\u2019s Hospital.\u00a0 However, the research and formal medical evaluations are performed through separate programs. People can choose to participate in, and be appropriate for, one or both options.\u00a0 To pre-screen individuals for either program (research enrollment or clinic visit), Dr. Engle and her team review clinical information provided through forms and medical records. This helps us to be sure that the desired study and\/or clinic participation are appropriate.<\/p>\n
Continue reading below to learn more or click on the buttons to move to a specific section.<\/p>\n
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<\/p>\n<\/p>\nEnrolling Into Our Research<\/div>\n <\/div>\n
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<\/p>\n<\/p>\nAttending Ocular CCDD Clinic<\/div>\n <\/div>\n
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<\/p>\n<\/p>\nFrequently Asked Questions (FAQs)<\/div>\n <\/div>\n
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[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”Enrolling” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” link_option_url=”#CCDDs” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/08\/new.MBS_.lab_.jpg” title_text=”new.MBS.lab” align=”center” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″ width=”57%” module_alignment=”center” height=”362px”][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” width=”100%” custom_margin=”-20px||” custom_padding=”0px|||217px|false|false”]<\/p>\n
Dr. Elizabeth Engle (center, front) and members of the Engle Lab commemorating Moebius Syndrome Awareness Day 2020.<\/em><\/p>\n[\/et_pb_text][et_pb_text module_id=”genetics” _builder_version=”4.5.3″ max_width=”100%” custom_margin=”|-571px||||”]<\/p>\n
Enrolling in Engle Lab Research Studies<\/h2>\n
The Engle Lab\u2019s research enrollment goals are to (1) enroll participants who are born with complex eye and facial movement disorders or disorders of lower cranial nerve function together with family members and\u00a0 (2) enroll families in which three or more relatives are diagnosed with strabismus.\u00a0 Patients, parents, health care providers and other researchers all refer individuals to us for enrollment.<\/p>\n
Examples of disorders we study:<\/h3>\n\n- Complex congenital eye and eyelid movement disorders:<\/li>\n
\n- Congenital Fibrosis of the Extraocular Muscles (CFEOM)<\/li>\n
- Congenital ptosis<\/li>\n
- Marcus Gunn Jaw Winking syndrome (MGJWS)<\/li>\n
- Duane syndrome \/ Duane retraction syndrome (DRS)<\/li>\n
- Horizontal Gaze Palsy (HGP)<\/li>\n
- Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)<\/li>\n
- Moebius syndrome \/ Moebius sequence (MBS)<\/li>\n
- Congenital 3rd, 4th, or 6th nerve palsy<\/li>\n
- Ocular and lid synkinesis<\/li>\n
- Any other complex congenital eye or lid movement disorder (yet to be defined)<\/li>\n<\/ul>\n
- Congenital facial weakness or palsy<\/li>\n
\n- Isolated congenital facial weakness<\/li>\n
- Syndromic congenital facial weakness<\/li>\n
- Moebius syndrome<\/li>\n<\/ul>\n
- Congenital disorders of lower cranial nerves<\/li>\n
\n- Examples include disorders of tongue movement, chewing, or swallowing<\/li>\n<\/ul>\n
- Familial Strabismus<\/li>\n
\n- Families in which 3 or more relatives are diagnosed with strabismus, including but not limited to esotropia, infantile esotropia, accommodative esotropia, intermittent esotropia, and exotropia.<\/li>\n<\/ul>\n<\/ul>\n
The conditions we study generally cause symptoms that are noted in infancy or early childhood, even if an official diagnosis is not made for several years. If symptoms begin in adulthood or are due to surgery or trauma, our study is unlikely to be appropriate.\u00a0 Please do not hesitate to contact us with questions about eligibility.<\/p>\n
What participation includes:<\/h3>\n\n- All participation steps can be arranged remotely. Travel to Boston is not required.<\/li>\n
- There are no fees nor costs to participate.<\/li>\n
- We can explain the study and enrollment process and answer any questions via telephone, video conferencing, or secure email. If a potential participant is being seen at Boston Children\u2019s Hospital, we may also be able to meet in person.<\/li>\n
- Enrollment is ongoing and rolling with no predetermined end date.<\/li>\n
- Our goal is to enroll all affected and unaffected close members of a family (such as parents and siblings) when feasible.<\/li>\n
- Enrollment consists of four steps: 1) Screening, 2) Consenting, 3) Request for medical records, imaging, and test results, and 4) Sampling.<\/li>\n<\/ul>\n
1. Screening<\/h4>\n
Receiving initial information about potential participants through a screening form allows us to determine if enrollment in our study is appropriate.\u00a0 We gather this information through an Intake Form<\/a>\u00a0that can be downloaded or collected by phone. Once completed, please return the form via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a><\/p>\n2. Consenting<\/h4>\n
Informed consent from each participant is obtained. Informed consent is a legal term. It means that the potential participant is fully aware of the facts and risks of participating in the research study before agreeing to it. An Engle Lab staff member will obtain consent by phone or videoconference. This session provides an opportunity for the potential participant and family to ask questions and for us to be sure that everyone is aware of the study process. For minors or people under guardianship, in addition to consent, we may obtain assent from the participant. For families with appointments at Boston Children\u2019s Hospital, in-person consenting may also be an option.\u00a0 Depending on the discussion and number of questions, the consenting process typically takes 10-20 minutes.\u00a0 Participants are given an opportunity to read the consent carefully prior to the discussion, and forms can be emailed directly and\/or included in an enrollment kit.\u00a0 Once all questions have been satisfactorily addressed and consenting has been completed and is on file, we move on to sampling.<\/p>\n
3. Request for medical records, imaging, and test results<\/h4>\n
In addition to the initial intake form, we require additional clinical information to successfully study an enrolled individual or family.\u00a0 This information can be obtained throughout the enrollment and participation process. We request that the participants fill out the forms below: clinical history form, medical history form, and medical records release form that provide permission for us to request medical records and copies of imaging studies (typically MRI scans). Please note that some facilities require that patients use that facility\u2019s specific release form; information on our form should help you to complete any requests to share records with us. We also ask for photos and videos of eye and facial movements (some of which can be done online). Please download these forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a>\u00a0Links to additional forms including a sample consent are also available in the FAQs below.<\/p>\nWhat forms or information are required?\u00a0<\/em><\/h5>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
4. Sampling<\/h4>\n
The Engle Lab genetic studies typically require a saliva or blood sample from each participant.\u00a0 Once received by the lab, this sample is used to extract DNA. Saliva samples can be obtained in the comfort of the home, using special collection tubes that we can mail, along with some paperwork, directly to you or to your doctor\u2019s office. These samples and paperwork are then returned to the lab using our mailers at our cost.\u00a0 As with the other steps, if you are receiving care at Boston Children\u2019s Hospital, we can arrange to meet with you in person to complete sampling. On rare occasions when the lab cannot successfully obtain adequate DNA from a sample, we may need to request a repeat saliva sample or an alternative sample, such as via a blood draw.\u00a0 On other rare occasions a participant may prefer to provide a blood sample rather than a saliva sample.<\/p>\n
Please do not hesitate to contact us with any questions about the enrollment process.<\/strong><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
BACK TO TOP ^<\/a><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ module_id=”CCDDClinic” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/2012_Chair-celebration_Engle-Hunter.jpg” title_text=”2012_Chair celebration_Engle-Hunter” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. Elizabeth Engle and Dr. David Hunter.<\/em><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/3.-patient-study-button-scaled.jpg” title_text=”3. patient & study button” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n
Dr. David Hunter and Sarah Mackinnon (orthoptist) evaluating a patient at the Moebius Syndrome Foundation (MSF) Annual Meeting.<\/em><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.9.7″]<\/p>\n
Attending the Ocular CCDD Clinic<\/h2>\n
Elizabeth Engle<\/a> MD (Neurologist),\u00a0David Hunter<\/a>\u00a0 MD, PhD (Ophthalmologist-in-Chief),\u00a0Sarah MacKinnon<\/a>\u00a0MSc, OC(C), CO, COMT (Chief Orthoptist) and Brenda Barry<\/a>\u00a0MS CGC (Genetic Counselor) hold a combined outpatient clinic in which they evaluate individuals of all ages who have, or may have, an ocular CCDD.<\/p>\nCCDD clinic patients undergo ophthalmological and neurological consultations. Diagnosis, etiologies, prognosis, treatment options, genetic testing, and research enrollment options may be discussed at the clinic visit. Drs. Hunter and Engle will both be present to answer questions and address concerns.<\/p>\n
Appointments generally last 3 to 4 hours and the clinic is typically held the first Monday afternoon of the month in the Ophthalmology Department, Fegan 4, Boston Children\u2019s Hospital main campus, 300 Longwood Avenue, Boston, MA.<\/p>\n
Screening<\/h3>\n
We request information in advance of CCDD clinic visits. This information allows us to be certain that the patient is seen by the correct specialists and allows us to review the patient\u2019s history in advance. If you or a family member or patient wishes to be screened for CCDD clinic, please download and fill out the four forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail<\/a>.<\/p>\n\n- Intake Form<\/a><\/li>\n
- Clinical History Form<\/a><\/span><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n<\/ul>\n
Please contact englegc.research@childrens.harvard.edu<\/a>\u00a0for more information about the CCDD clinic and\/or to schedule an appointment.\u00a0 If an appointment is appropriate, you will be connected with administrative staff at the hospital to obtain a medical records number and to receive help regarding any billing and insurance questions.<\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n
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Frequently Asked Questions (FAQs)<\/h2>\nWhat is strabismus?<\/em><\/h4>\nStrabismus refers to eyes that are misaligned.\u00a0 This misalignment, or inability of the eyes to coordinate movements, may be present from infancy or develop over time and is thought to affect 1-5% of the general population.\u00a0 We are still learning about strabismus, but we know it can be caused by problems with the eye muscles, the nerves that control these muscles, or problems with how the brain processes visual information.\u00a0 The Engle Lab studies familial strabismus of all types and complex strabismus syndromes that are present from birth or infancy.<\/p>\n
What is a CCDD?\u00a0<\/em><\/h4>\nCongenital Cranial Dysinnervation Disorders (CCDDs) are neurological conditions affecting one or more of the cranial motor nerves. The cranial motor nerves develop from the brain and connect to muscles and tissues to control functions such as movement of the eyes and eyelids, facial expression, blinking, chewing, and swallowing. CCDDs that impact eye movements, and often cause strabismus, are called ocular CCDDs.\u00a0 Ocular CCDDs include CFEOM (congenital fibrosis of extraocular muscles), Duane syndrome, 3rd, 4th, and 6th nerve palsy, Moebius syndrome, ocular synkinesis syndromes and horizontal gaze palsy with progressive scoliosis (HGPPS). Other CCDDs most prominently affect facial movements, resulting in congenital facial weakness.<\/p>\n
What genes are studied by the Engle Lab?<\/em><\/h4>\nThe Engle Lab has identified, characterized, and continues to study multiple genetic disorders that alter the development and function of the nerves and muscles critical for typical eye and facial movements.\u00a0 Some of the molecules and pathways we study are related to mutations in the following genes: KIF21A, TUBB3, TUBB2B, <\/em>and PHOX2A<\/em> that cause CFEOM; \u00a0CHN1, MAFB, HOXA1,<\/em> SALL4, <\/em>and ROBO3\u00a0 <\/em>that cause Duane syndrome \/ horizontal gaze palsy; and HOXB1 <\/em>that causes congenital facial weakness.<\/p>\nThe Engle Lab is also focused on identifying new, previously uncharacterized genetic causes of CCDDs.\u00a0 For this reason, our set-up and methods differ from those of commercial testing labs that exist to precisely test known genes.\u00a0 If your health care provider feels that a known genetic condition may explain the symptoms you or a family member are experiencing, genetic testing for that condition may now be commercially available because of past research successes.\u00a0 If so, it may be more efficient to directly pursue that testing in a clinical lab rather than enrolling in a research study that has an uncertain timeline for results and the need for repeated sampling and confirmation testing.<\/p>\n
Is there a cost to participants?<\/em><\/h4>\nThere is no cost to participate and travel is not required. There is also no compensation for participation in our study.<\/p>\n
What are the goals of the study?<\/em><\/h4>\nWe use DNA from participants to identify and study new genetic causes of CCDDs and impaired eye and facial movements. The clinical information helps us to understand what a gene does normally and what can result if it is mutated and thus not working normally. From a clinical standpoint, by understanding the genetic cause of a given CCDD we hope to improve diagnosis and treatment, and to provide accurate genetic counseling.<\/p>\n
What is the enrollment process?<\/em><\/h4>\nWe welcome contact by email, phone, or postal mail<\/a> from patients, parents, and healthcare providers to determine if someone is eligible for the study.\u00a0 Once we receive an inquiry and screening forms, research staff contact you to discuss enrollment or request additional information, review the consent form, and guide the sampling process.<\/p>\nWhat type of medical information is helpful?<\/em><\/h4>\nWe benefit from collecting details through interviews and forms completed by patients themselves or their health care providers, as well as through receipt of primary medical records.\u00a0 Typically, of greatest help are records related to ophthalmology, neurology, and genetics, including exam and surgical notes, testing results, and copies of brain\/eye imaging (especially MRI scans). We can also provide a link to an online web app, StrabisPIX<\/a>, developed by our colleagues in Ophthalmology at Boston Children\u2019s Hospital to capture photographs of eye positions.<\/p>\nWhat types of samples are needed for participation?<\/em><\/h4>\nWe generally start by obtaining DNA using a specialized saliva collection kit that we provide to families.\u00a0 Sometimes we may ask for a blood draw if collection of DNA using saliva is not successful or if we have a specific need for whole blood.\u00a0 We may also obtain already stored DNA and\/or tissue that may have been collected through a doctor\u2019s office and is no longer needed.\u00a0 Most commonly, only one sample is required.\u00a0 However, if the DNA is of poor quality, is used up over the course of the research, or we have a specialized project, we may reach out to enrolled participants to request additional samples, if they have provided consent for us to recontact them.<\/p>\n
Who can participate?<\/em><\/h4>\nWe need to enroll and obtain DNA from at least one family member diagnosed with a condition we study.\u00a0 If only one person in the family has the condition, we would likely request that the person\u2019s parents and siblings also enroll. If more than one person in the family has the condition, we would likely ask if all affected individuals and their immediate family members would enroll.\u00a0 This allows us to compare changes we find in the DNA of the persons with the diagnosis to the DNA of unaffected family members to best interpret genetic findings.\u00a0 However, we acknowledge that enrolling additional biological relatives is not always feasible. Importantly, we must consent each participant and receive their sample.<\/p>\n
What forms or information are required?\u00a0<\/em><\/h4>\nWe ask to receive back a general intake and 3 initial forms from people interested in the study. Other materials, including the consent and submission form, are provided by email and\/or with the enrollment kit. These forms may be downloaded by clicking below.\u00a0 They can be completed and returned by email<\/a> or regular mail<\/a>.<\/p>\n\n- Intake Form<\/span><\/a><\/li>\n
- Clinical History Form<\/a><\/li>\n
- Family History Form<\/span><\/a><\/li>\n
- Medical Records Release Form<\/span><\/a><\/li>\n
- Example Consent (this is an example and should not be used for enrollment)<\/span><\/a><\/li>\n
- Sample Submission Form<\/span><\/a><\/li>\n
- Participant Questionnaire (PQ)<\/span><\/a><\/li>\n<\/ul>\n
Are study participation and results confidential?<\/em><\/h4>\nOur lab collects DNA samples and medical information from persons and families with features indicating they have or may have a CCDD or familial strabismus.\u00a0 The information is kept confidential.\u00a0 Identifiable details are not shared with anyone outside of the Engle Lab without the specific permission of participants.\u00a0 No results are placed in the medical record of participating individuals or their families prior to clinical confirmation. We consent people to make sure everyone understands important details of the study and how we protect participant data.<\/p>\n
Can participants obtain results?<\/em><\/h4>\nAnalyses will be done in our research laboratory and so are considered investigational. This means that we cannot directly release results to a participant. However, participants can call or email us at any time to ask questions or to check in on the overall progress of the program. In addition, participants are given choices on the consent form to indicate if s\/he wishes to be informed about the availability of results. If we identify findings for a specific participant who has noted s\/he wished to be informed of significant results, we would attempt to contact the participant and\/or a designated medical provider (based on information obtained during enrollment or as updated by the participant).\u00a0 We would work with them to have our research findings confirmed by an authorized clinical laboratory which would then issue a report that would become part of the medical record and provide details about the results.\u00a0Our research findings are also shared through scientific publications. The results in such publications do not include any information that would permit identification of participants. We can provide copies of these publications on request.<\/p>\n
What are possible benefits of participation?<\/em><\/h4>\nEach and every participant contributes to the improved understanding of the CCDDs.\u00a0 Some participants may also learn about the genetic basis of their condition.<\/p>\n
How can I tell other people about this study?<\/em><\/h4>\nYou may tell people about this website and share all of our contact information with anyone you wish. You may also download and share\u00a0these pamphlets\u00a0about the research on cranial nerves<\/a> and on facial weakness and Moebius syndrome.<\/a><\/span><\/p>\n<\/em><\/h4>\n<\/em><\/h4>\nWhat other resources exist?<\/em><\/h4>\n\n- Adult Strabismus Q&A with Dr. Hunter<\/a><\/li>\n
- Clinical Trials<\/a><\/li>\n
- Boston Children\u2019s Hospital Clinical Trials<\/a><\/li>\n
- GeneReviews CFEOM<\/a><\/li>\n
- GeneReviews Duane Syndrome<\/a><\/li>\n
- Moebius Syndrome Foundation<\/a><\/li>\n<\/ul>\n
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The Engle Lab at the F.M. Kirby Neurobiology Center Patient & Study Participant ResourcesWelcome, we are glad you found us!\u00a0 You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information […]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\n
[et_pb_section fb_built=\"1\" admin_label=\"BKGD IMAGE\" _builder_version=\"4.5.0\" background_color=\"#000000\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" background_enable_image=\"off\" background_size=\"initial\" custom_padding=\"1px|0px|0|0px|false|false\" global_module=\"3860\" saved_tabs=\"all\"][et_pb_row _builder_version=\"4.5.0\" background_image=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/BANNER.png\" min_height=\"353px\" custom_margin=\"|auto||161px||\" custom_padding=\"17px|0px|255px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"home_header\" _builder_version=\"4.5.0\" text_font=\"||||||||\" header_font=\"||||||||\" min_height=\"39px\" custom_css_main_element=\"color:#ffffff;||line-height:0.95em;||font-family:el messiri;||font-size:44px;||font-weight:normal;\" inline_fonts=\"Merriweather,El Messiri,Georgia\"]<\/div>\n<\/div>\nThe Engle Lab<\/div>\nat the FM Kirby Neurobiology Center<\/div>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"4.4.5\" background_color=\"#ffffff\" custom_padding=\"0|0px|0|0px|false|false\"][et_pb_row _builder_version=\"4.3.4\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text _builder_version=\"4.4.5\"]<\/span><\/p>\nScience & Research<\/span><\/p>[\/et_pb_text][et_pb_text _builder_version=\"4.4.5\"]For a full list of Engle Lab publications, please click here<\/a>. To request a PDF of a lab publication, email engle.admin@childrens.harvard.edu<\/a>.<\/p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"3.22.3\" custom_padding=\"0|0px|47.625px|0|false|false\"][et_pb_row column_structure=\"1_3,1_3,1_3\" _builder_version=\"4.5.0\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"1_3\" _builder_version=\"4.5.0\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#CCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" background_enable_color=\"off\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#Transcriptomics\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Transcriptomic and Epigenomic Analyses of the Developing Brainstem<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsCCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of CCDDs<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Disease Modeling<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][et_pb_column type=\"1_3\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#GeneticsEsotropiaExotropia\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\" min_height=\"242px\" link_option_url=\"#genetics\"] Genetics & Genomics of Esotropia & Exotropia<\/div> <\/div> <\/a><\/div>[\/et_pb_code][et_pb_code module_id=\"#DiseaseModeling\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Imaging<\/div> <\/div> <\/a><\/div>[\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=\"topic-two\" _builder_version=\"3.25\"][et_pb_column type=\"4_4\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_divider _builder_version=\"3.23.4\" height=\"0px\"][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=\"1_2,1_2\" module_id=\"CCDDs\" _builder_version=\"4.5.0\" custom_padding=\"30px|0px|25.2344px|0px|false|false\" link_option_url=\"#CCDDs\"][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_image src=\"https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/CCDD-image.001-2.jpeg\" title_text=\"CCDD image.001\" align_tablet=\"center\" align_phone=\"\" align_last_edited=\"on|desktop\" _builder_version=\"4.5.0\"][\/et_pb_image][et_pb_text _builder_version=\"3.27.4\" text_font=\"||||||||\" text_font_size=\"1px\" custom_margin=\"-20px||\" custom_padding=\"0px||\"]Optional image caption and attribution<\/em><\/p>[\/et_pb_text][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]Publications<\/h3>\n
Publication 1 ><\/p>\n
Publication 2 ><\/p>[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"]
Congenital Cranial Dysinnervation Disorders (CCDDs)<\/h2>\n
We humans are defined, in part, by the nuanced and coordinated ocular and facial movements that are fundamental to our vision and social communication. The Engle Lab studies human developmental disorders that perturb these eye and face movements as a framework to understand how neurons are specified and how cranial neural circuits are formed. We identify human disorders of eye and face movement, define their genetic etiologies, and study the developmental pathology and disease mechanism in vitro and in animal models. We also study the normal development of cranial motor neurons and their axonal processes. Our research has led to the definition of the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are birth defects in which cranial motor neurons or their axonal processes fail to develop correctly. While the CCDDs include all cranial motor nerves, the lab focuses in particular on disorders of oculomotor (cranial nerve 3), trochlear (cranial nerve 4), abducens (cranial nerve 6) and\/or facial (cranial nerve 7) development. The ocular CCDDs result in the inability to raise the eyelid(s) or to move the eye(s) in one or more directions of gaze. The facial CCDDs result in unilateral or bilateral h bvdsafacial weakness. We also study the genetics of esotropia and exotropia (common or comitant forms of strabismus), as described below<\/a>.<\/span><\/p>\nThe lab has found that human disorders of cranial motor neuron development provide a unique and powerful system to study Mendelian genetics and neural connectivity:<\/span><\/p>\n\n- Each cranial motor nucleus contains a small number of motor neurons.<\/span><\/li>\n
- Each cranial motor nerve has straightforward tractable developmental anatomy that can be visualized in three dimensions.<\/span><\/li>\n
- Errors in development result in human phenotypes that are present at birth, lifelong, visible to the examiner, and stereotypic in presentation.<\/span><\/li>\n
- All higher vertebrates have 12 highly conserved cranial nerves, providing consistent translation to model organisms for developmental and mechanistic studies.<\/span><\/li>\n
- The Engle Lab has amassed a remarkable Mendelian cohort of research participants, leading to a high likelihood that we will identify multiple disease alleles with which to document causality of a new genetic disorder.<\/span><\/li>\n<\/ul>[\/et_pb_text][et_pb_text _builder_version=\"3.27.4\"]
Patient & Study Participant Resources<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.5.3″ custom_padding=”0|0px|47.625px|0|false|false”][et_pb_row _builder_version=”4.5.0″ _module_preset=”default” custom_padding=”||0px|||”][et_pb_column type=”4_4″ _builder_version=”4.5.0″ _module_preset=”default”][et_pb_text _builder_version=”4.5.3″ _module_preset=”default”]<\/p>\n You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information will address questions you may have about enrolling in our research and\/or attending our CCDD Consultation Clinic.<\/p>\n From a research standpoint, the Engle Lab strives to better understand the neurogenetic basis of cranial nerve development and function.\u00a0 This is done through gene discovery and basic research described in the Science section<\/a> of our website. Gene discovery requires the enrollment and participation of individuals and families diagnosed with rare conditions involving atypical or limited eye and facial movements. These conditions include both defined or undefined congenital cranial dysinnervation disorders (CCDDs)<\/a>\u00a0and familial strabismus<\/a>.<\/p>\n Dr. Engle and her colleagues also oversee and participate in a multi-disciplinary, second-opinion consultation clinic at Boston Children\u2019s Hospital for children and adults diagnosed with ocular CCDDs. This clinic is staffed by two physicians, Dr. Elizabeth Engle, a child neurologist and pediatrician, and Dr. David Hunter, an ophthalmologist, as well as an\u00a0orthoptist <\/a>and genetic counselor<\/a>.\u00a0More information on this clinic is provided in\u00a0\u00a0“Attending the Ocular CCDD Clinic”<\/a>.<\/p>\n There is overlap between the conditions studied by the Engle Lab and the conditions seen through the CCDD clinic at Boston Children\u2019s Hospital.\u00a0 However, the research and formal medical evaluations are performed through separate programs. People can choose to participate in, and be appropriate for, one or both options.\u00a0 To pre-screen individuals for either program (research enrollment or clinic visit), Dr. Engle and her team review clinical information provided through forms and medical records. This helps us to be sure that the desired study and\/or clinic participation are appropriate.<\/p>\n Continue reading below to learn more or click on the buttons to move to a specific section.<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.9.7″ custom_margin=”0px|auto|0px|auto|false|false” custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_3″ _builder_version=”4.5.0″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#CCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ background_enable_color=”off” max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n <\/div>\n <\/a><\/div>\n [\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsCCDDs” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n <\/div>\n <\/a><\/div>\n [\/et_pb_code][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_code module_id=”#GeneticsEsotropiaExotropia” module_class=”circular underlay_text basetext underlay” _builder_version=”4.9.7″ max_width=”75%” max_width_tablet=”45%” max_width_phone=”75%” max_width_last_edited=”on|tablet” module_alignment=”center” min_height=”242px” link_option_url=”#genetics” hover_enabled=”0″ custom_padding=”||0px||false|false” sticky_enabled=”0″ custom_margin=”||0px||false|false”]<\/p>\n <\/div>\n <\/a><\/div>\n [\/et_pb_code][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”Enrolling” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” link_option_url=”#CCDDs” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/08\/new.MBS_.lab_.jpg” title_text=”new.MBS.lab” align=”center” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″ width=”57%” module_alignment=”center” height=”362px”][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” width=”100%” custom_margin=”-20px||” custom_padding=”0px|||217px|false|false”]<\/p>\n Dr. Elizabeth Engle (center, front) and members of the Engle Lab commemorating Moebius Syndrome Awareness Day 2020.<\/em><\/p>\n [\/et_pb_text][et_pb_text module_id=”genetics” _builder_version=”4.5.3″ max_width=”100%” custom_margin=”|-571px||||”]<\/p>\n The Engle Lab\u2019s research enrollment goals are to (1) enroll participants who are born with complex eye and facial movement disorders or disorders of lower cranial nerve function together with family members and\u00a0 (2) enroll families in which three or more relatives are diagnosed with strabismus.\u00a0 Patients, parents, health care providers and other researchers all refer individuals to us for enrollment.<\/p>\n The conditions we study generally cause symptoms that are noted in infancy or early childhood, even if an official diagnosis is not made for several years. If symptoms begin in adulthood or are due to surgery or trauma, our study is unlikely to be appropriate.\u00a0 Please do not hesitate to contact us with questions about eligibility.<\/p>\n Receiving initial information about potential participants through a screening form allows us to determine if enrollment in our study is appropriate.\u00a0 We gather this information through an Intake Form<\/a>\u00a0that can be downloaded or collected by phone. Once completed, please return the form via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a><\/p>\n Informed consent from each participant is obtained. Informed consent is a legal term. It means that the potential participant is fully aware of the facts and risks of participating in the research study before agreeing to it. An Engle Lab staff member will obtain consent by phone or videoconference. This session provides an opportunity for the potential participant and family to ask questions and for us to be sure that everyone is aware of the study process. For minors or people under guardianship, in addition to consent, we may obtain assent from the participant. For families with appointments at Boston Children\u2019s Hospital, in-person consenting may also be an option.\u00a0 Depending on the discussion and number of questions, the consenting process typically takes 10-20 minutes.\u00a0 Participants are given an opportunity to read the consent carefully prior to the discussion, and forms can be emailed directly and\/or included in an enrollment kit.\u00a0 Once all questions have been satisfactorily addressed and consenting has been completed and is on file, we move on to sampling.<\/p>\n In addition to the initial intake form, we require additional clinical information to successfully study an enrolled individual or family.\u00a0 This information can be obtained throughout the enrollment and participation process. We request that the participants fill out the forms below: clinical history form, medical history form, and medical records release form that provide permission for us to request medical records and copies of imaging studies (typically MRI scans). Please note that some facilities require that patients use that facility\u2019s specific release form; information on our form should help you to complete any requests to share records with us. We also ask for photos and videos of eye and facial movements (some of which can be done online). Please download these forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail.<\/a>\u00a0Links to additional forms including a sample consent are also available in the FAQs below.<\/p>\n The Engle Lab genetic studies typically require a saliva or blood sample from each participant.\u00a0 Once received by the lab, this sample is used to extract DNA. Saliva samples can be obtained in the comfort of the home, using special collection tubes that we can mail, along with some paperwork, directly to you or to your doctor\u2019s office. These samples and paperwork are then returned to the lab using our mailers at our cost.\u00a0 As with the other steps, if you are receiving care at Boston Children\u2019s Hospital, we can arrange to meet with you in person to complete sampling. On rare occasions when the lab cannot successfully obtain adequate DNA from a sample, we may need to request a repeat saliva sample or an alternative sample, such as via a blood draw.\u00a0 On other rare occasions a participant may prefer to provide a blood sample rather than a saliva sample.<\/p>\n Please do not hesitate to contact us with any questions about the enrollment process.<\/strong><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n BACK TO TOP ^<\/a><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_2,1_2″ module_id=”CCDDClinic” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/2012_Chair-celebration_Engle-Hunter.jpg” title_text=”2012_Chair celebration_Engle-Hunter” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n Dr. Elizabeth Engle and Dr. David Hunter.<\/em><\/p>\n [\/et_pb_text][et_pb_image src=”https:\/\/kirbyneuro.org\/EngleLab\/wp-content\/uploads\/2020\/07\/3.-patient-study-button-scaled.jpg” title_text=”3. patient & study button” align_tablet=”center” align_phone=”” align_last_edited=”on|desktop” _builder_version=”4.5.0″][\/et_pb_image][et_pb_text _builder_version=”4.5.0″ text_font=”||||||||” text_font_size=”1px” custom_margin=”-20px||” custom_padding=”0px||”]<\/p>\n Dr. David Hunter and Sarah Mackinnon (orthoptist) evaluating a patient at the Moebius Syndrome Foundation (MSF) Annual Meeting.<\/em><\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.9.7″]<\/p>\n Elizabeth Engle<\/a> MD (Neurologist),\u00a0David Hunter<\/a>\u00a0 MD, PhD (Ophthalmologist-in-Chief),\u00a0Sarah MacKinnon<\/a>\u00a0MSc, OC(C), CO, COMT (Chief Orthoptist) and Brenda Barry<\/a>\u00a0MS CGC (Genetic Counselor) hold a combined outpatient clinic in which they evaluate individuals of all ages who have, or may have, an ocular CCDD.<\/p>\n CCDD clinic patients undergo ophthalmological and neurological consultations. Diagnosis, etiologies, prognosis, treatment options, genetic testing, and research enrollment options may be discussed at the clinic visit. Drs. Hunter and Engle will both be present to answer questions and address concerns.<\/p>\n Appointments generally last 3 to 4 hours and the clinic is typically held the first Monday afternoon of the month in the Ophthalmology Department, Fegan 4, Boston Children\u2019s Hospital main campus, 300 Longwood Avenue, Boston, MA.<\/p>\n We request information in advance of CCDD clinic visits. This information allows us to be certain that the patient is seen by the correct specialists and allows us to review the patient\u2019s history in advance. If you or a family member or patient wishes to be screened for CCDD clinic, please download and fill out the four forms by clicking below. Once completed please return them to us via email to englegc.research@childrens.harvard.edu<\/a> or by regular mail<\/a>.<\/p>\n Please contact englegc.research@childrens.harvard.edu<\/a>\u00a0for more information about the CCDD clinic and\/or to schedule an appointment.\u00a0 If an appointment is appropriate, you will be connected with administrative staff at the hospital to obtain a medical records number and to receive help regarding any billing and insurance questions.<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n BACK TO TOP ^<\/a><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”topic-two” _builder_version=”4.9.7″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_divider _builder_version=”4.9.7″ height_last_edited=”off|desktop” max_height=”1px”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”FAQs” _builder_version=”4.9.7″ custom_padding=”0px|0px|0px|0px|false|false” hover_enabled=”0″ sticky_enabled=”0″][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text module_id=”genetics” _builder_version=”4.5.5″]<\/p>\n Strabismus refers to eyes that are misaligned.\u00a0 This misalignment, or inability of the eyes to coordinate movements, may be present from infancy or develop over time and is thought to affect 1-5% of the general population.\u00a0 We are still learning about strabismus, but we know it can be caused by problems with the eye muscles, the nerves that control these muscles, or problems with how the brain processes visual information.\u00a0 The Engle Lab studies familial strabismus of all types and complex strabismus syndromes that are present from birth or infancy.<\/p>\n Congenital Cranial Dysinnervation Disorders (CCDDs) are neurological conditions affecting one or more of the cranial motor nerves. The cranial motor nerves develop from the brain and connect to muscles and tissues to control functions such as movement of the eyes and eyelids, facial expression, blinking, chewing, and swallowing. CCDDs that impact eye movements, and often cause strabismus, are called ocular CCDDs.\u00a0 Ocular CCDDs include CFEOM (congenital fibrosis of extraocular muscles), Duane syndrome, 3rd, 4th, and 6th nerve palsy, Moebius syndrome, ocular synkinesis syndromes and horizontal gaze palsy with progressive scoliosis (HGPPS). Other CCDDs most prominently affect facial movements, resulting in congenital facial weakness.<\/p>\n The Engle Lab has identified, characterized, and continues to study multiple genetic disorders that alter the development and function of the nerves and muscles critical for typical eye and facial movements.\u00a0 Some of the molecules and pathways we study are related to mutations in the following genes: KIF21A, TUBB3, TUBB2B, <\/em>and PHOX2A<\/em> that cause CFEOM; \u00a0CHN1, MAFB, HOXA1,<\/em> SALL4, <\/em>and ROBO3\u00a0 <\/em>that cause Duane syndrome \/ horizontal gaze palsy; and HOXB1 <\/em>that causes congenital facial weakness.<\/p>\n The Engle Lab is also focused on identifying new, previously uncharacterized genetic causes of CCDDs.\u00a0 For this reason, our set-up and methods differ from those of commercial testing labs that exist to precisely test known genes.\u00a0 If your health care provider feels that a known genetic condition may explain the symptoms you or a family member are experiencing, genetic testing for that condition may now be commercially available because of past research successes.\u00a0 If so, it may be more efficient to directly pursue that testing in a clinical lab rather than enrolling in a research study that has an uncertain timeline for results and the need for repeated sampling and confirmation testing.<\/p>\n There is no cost to participate and travel is not required. There is also no compensation for participation in our study.<\/p>\n We use DNA from participants to identify and study new genetic causes of CCDDs and impaired eye and facial movements. The clinical information helps us to understand what a gene does normally and what can result if it is mutated and thus not working normally. From a clinical standpoint, by understanding the genetic cause of a given CCDD we hope to improve diagnosis and treatment, and to provide accurate genetic counseling.<\/p>\n We welcome contact by email, phone, or postal mail<\/a> from patients, parents, and healthcare providers to determine if someone is eligible for the study.\u00a0 Once we receive an inquiry and screening forms, research staff contact you to discuss enrollment or request additional information, review the consent form, and guide the sampling process.<\/p>\n We benefit from collecting details through interviews and forms completed by patients themselves or their health care providers, as well as through receipt of primary medical records.\u00a0 Typically, of greatest help are records related to ophthalmology, neurology, and genetics, including exam and surgical notes, testing results, and copies of brain\/eye imaging (especially MRI scans). We can also provide a link to an online web app, StrabisPIX<\/a>, developed by our colleagues in Ophthalmology at Boston Children\u2019s Hospital to capture photographs of eye positions.<\/p>\n We generally start by obtaining DNA using a specialized saliva collection kit that we provide to families.\u00a0 Sometimes we may ask for a blood draw if collection of DNA using saliva is not successful or if we have a specific need for whole blood.\u00a0 We may also obtain already stored DNA and\/or tissue that may have been collected through a doctor\u2019s office and is no longer needed.\u00a0 Most commonly, only one sample is required.\u00a0 However, if the DNA is of poor quality, is used up over the course of the research, or we have a specialized project, we may reach out to enrolled participants to request additional samples, if they have provided consent for us to recontact them.<\/p>\n We need to enroll and obtain DNA from at least one family member diagnosed with a condition we study.\u00a0 If only one person in the family has the condition, we would likely request that the person\u2019s parents and siblings also enroll. If more than one person in the family has the condition, we would likely ask if all affected individuals and their immediate family members would enroll.\u00a0 This allows us to compare changes we find in the DNA of the persons with the diagnosis to the DNA of unaffected family members to best interpret genetic findings.\u00a0 However, we acknowledge that enrolling additional biological relatives is not always feasible. Importantly, we must consent each participant and receive their sample.<\/p>\n We ask to receive back a general intake and 3 initial forms from people interested in the study. Other materials, including the consent and submission form, are provided by email and\/or with the enrollment kit. These forms may be downloaded by clicking below.\u00a0 They can be completed and returned by email<\/a> or regular mail<\/a>.<\/p>\n Our lab collects DNA samples and medical information from persons and families with features indicating they have or may have a CCDD or familial strabismus.\u00a0 The information is kept confidential.\u00a0 Identifiable details are not shared with anyone outside of the Engle Lab without the specific permission of participants.\u00a0 No results are placed in the medical record of participating individuals or their families prior to clinical confirmation. We consent people to make sure everyone understands important details of the study and how we protect participant data.<\/p>\n Analyses will be done in our research laboratory and so are considered investigational. This means that we cannot directly release results to a participant. However, participants can call or email us at any time to ask questions or to check in on the overall progress of the program. In addition, participants are given choices on the consent form to indicate if s\/he wishes to be informed about the availability of results. If we identify findings for a specific participant who has noted s\/he wished to be informed of significant results, we would attempt to contact the participant and\/or a designated medical provider (based on information obtained during enrollment or as updated by the participant).\u00a0 We would work with them to have our research findings confirmed by an authorized clinical laboratory which would then issue a report that would become part of the medical record and provide details about the results.\u00a0Our research findings are also shared through scientific publications. The results in such publications do not include any information that would permit identification of participants. We can provide copies of these publications on request.<\/p>\n Each and every participant contributes to the improved understanding of the CCDDs.\u00a0 Some participants may also learn about the genetic basis of their condition.<\/p>\n You may tell people about this website and share all of our contact information with anyone you wish. You may also download and share\u00a0these pamphlets\u00a0about the research on cranial nerves<\/a> and on facial weakness and Moebius syndrome.<\/a><\/span><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row module_id=”LabAlumni” _builder_version=”4.9.7″ custom_padding=”0px||0px||false|false”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″]<\/p>\n BACK TO TOP ^<\/a><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" The Engle Lab at the F.M. Kirby Neurobiology Center Patient & Study Participant ResourcesWelcome, we are glad you found us!\u00a0 You may have found this web page because you, a family member, or your patient, have\/has been diagnosed with a rare condition affecting eye and\/or facial movements.\u00a0 If so, we hope that the following information […]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\n <\/span><\/p>\n Science & Research<\/span><\/p>[\/et_pb_text][et_pb_text _builder_version=\"4.4.5\"] For a full list of Engle Lab publications, please click here<\/a>. To request a PDF of a lab publication, email engle.admin@childrens.harvard.edu<\/a>.<\/p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=\"1\" _builder_version=\"3.22.3\" custom_padding=\"0|0px|47.625px|0|false|false\"][et_pb_row column_structure=\"1_3,1_3,1_3\" _builder_version=\"4.5.0\" custom_padding=\"0|0px|30px|0px|false|false\"][et_pb_column type=\"1_3\" _builder_version=\"4.5.0\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_code module_id=\"#CCDDs\" module_class=\"circular underlay_text basetext underlay\" _builder_version=\"4.5.0\" background_enable_color=\"off\" max_width=\"85%\" max_width_tablet=\"45%\" max_width_phone=\"75%\" max_width_last_edited=\"on|tablet\" module_alignment=\"center\"] Optional image caption and attribution<\/em><\/p>[\/et_pb_text][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"] Publication 1 ><\/p>\n Publication 2 ><\/p>[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_2\" _builder_version=\"3.25\" custom_padding=\"|||\" custom_padding__hover=\"|||\"][et_pb_text module_id=\"genetics\" _builder_version=\"4.5.0\"] We humans are defined, in part, by the nuanced and coordinated ocular and facial movements that are fundamental to our vision and social communication. The Engle Lab studies human developmental disorders that perturb these eye and face movements as a framework to understand how neurons are specified and how cranial neural circuits are formed. We identify human disorders of eye and face movement, define their genetic etiologies, and study the developmental pathology and disease mechanism in vitro and in animal models. We also study the normal development of cranial motor neurons and their axonal processes. Our research has led to the definition of the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are birth defects in which cranial motor neurons or their axonal processes fail to develop correctly. While the CCDDs include all cranial motor nerves, the lab focuses in particular on disorders of oculomotor (cranial nerve 3), trochlear (cranial nerve 4), abducens (cranial nerve 6) and\/or facial (cranial nerve 7) development. The ocular CCDDs result in the inability to raise the eyelid(s) or to move the eye(s) in one or more directions of gaze. The facial CCDDs result in unilateral or bilateral h bvdsafacial weakness. We also study the genetics of esotropia and exotropia (common or comitant forms of strabismus), as described below<\/a>.<\/span><\/p>\n The lab has found that human disorders of cranial motor neuron development provide a unique and powerful system to study Mendelian genetics and neural connectivity:<\/span><\/p>\nWelcome, we are glad you found us!\u00a0<\/strong><\/h2>\n
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How can I participate or become involved?<\/h2>\n
<\/p>\n <\/p>\n <\/p>\nEnrolling in Engle Lab Research Studies<\/h2>\n
Examples of disorders we study:<\/h3>\n
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What participation includes:<\/h3>\n
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1. Screening<\/h4>\n
2. Consenting<\/h4>\n
3. Request for medical records, imaging, and test results<\/h4>\n
What forms or information are required?\u00a0<\/em><\/h5>\n
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4. Sampling<\/h4>\n
Attending the Ocular CCDD Clinic<\/h2>\n
Screening<\/h3>\n
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Frequently Asked Questions (FAQs)<\/h2>\n
What is strabismus?<\/em><\/h4>\n
What is a CCDD?\u00a0<\/em><\/h4>\n
What genes are studied by the Engle Lab?<\/em><\/h4>\n
Is there a cost to participants?<\/em><\/h4>\n
What are the goals of the study?<\/em><\/h4>\n
What is the enrollment process?<\/em><\/h4>\n
What type of medical information is helpful?<\/em><\/h4>\n
What types of samples are needed for participation?<\/em><\/h4>\n
Who can participate?<\/em><\/h4>\n
What forms or information are required?\u00a0<\/em><\/h4>\n
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Are study participation and results confidential?<\/em><\/h4>\n
Can participants obtain results?<\/em><\/h4>\n
What are possible benefits of participation?<\/em><\/h4>\n
How can I tell other people about this study?<\/em><\/h4>\n
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What other resources exist?<\/em><\/h4>\n
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Publications<\/h3>\n
Congenital Cranial Dysinnervation Disorders (CCDDs)<\/h2>\n
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