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Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies

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ClinicalTrials.gov Identifier: NCT03059420
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : September 26, 2022
Howard Hughes Medical Institute
National Eye Institute (NEI)
Information provided by (Responsible Party):
Elizabeth Engle, Boston Children's Hospital

Brief Summary:
The purpose of this study is to identify genes associated with impaired development and function of the cranial nerves and brainstem, which may result in misalignment of the eyes (strabismus) and related conditions.

Condition or disease
Congenital Fibrosis of Extraocular Muscles Duane Retraction Syndrome Duane Radial Ray Syndrome Mobius Syndrome Brown Syndrome Marcus Gunn Syndrome Strabismus Congenital Horizontal Gaze Palsy Horizontal Gaze Palsy With Progressive Scoliosis Facial Palsy Facial Paresis, Hereditary, Congenital Third Nerve Palsy Fourth Nerve Palsy Sixth Nerve Palsy Synkinesis Ocular Motility Disorders Levator-Medial Rectus Synkinesis Athabaskan Brainstem Dysgenesis Tongue Paralysis Ninth Nerve Disorder Fifth Nerve Palsy Seventh Nerve Palsy Eleventh Nerve Disorder Twelfth Nerve Disorder Vagus Nerve Paralysis Moebius Sequence

Detailed Description:

If left untreated or unrecognized, strabismus or misalignment of the eyes, can impair the development of normal vision and is recognized to be an inherited trait in some families. The Engle Lab has investigated the genetics of complex and common strabismus and eyelid movement disorders for over 10 years and the lab's interests have expanded to include Congenital Cranial Dysinnervation Disorders (CCDDs) which are neurological disorders affecting one or more of the 12 cranial nerves. Cranial nerves control bodily functions such as movement of the eyes, transmission of visual information, smell, facial sensation, facial expression, blinking, hearing, balance, taste, chewing and swallowing.

Based on genetic studies on individuals with eye movement and eyelid disorders, the lab learned that some individuals have additional ocular defects, vascular, limb and other abnormalities. In addition, in some families relatives who carry the gene mutation may manifest the familial syndrome by having only some additional features but NOT the oculomotility disorder. Therefore, to gain greater understanding of the spectrum of the disorders being investigated, we may also enroll individuals without eye movement or lid defects who have symptoms associated with mutations in congenital cranial dysinnervation disorder (CCDD) genes.

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Study Type : Observational
Estimated Enrollment : 20000 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies
Actual Study Start Date : February 1, 2004
Estimated Primary Completion Date : January 2027
Estimated Study Completion Date : January 2027

Primary Outcome Measures :
  1. Identifying and characterizing genes important in normal development and function of the ocular motility system, cranial nerves and brainstem and associated with congenital cranial dysinnervation disorders and related anomalies. [ Time Frame: Ongoing ]
    This is an observational, descriptive study with no interventions geared towards identifying novel genes and characterizing their function, expression and impact on human cranial nerve development and disease. As genes previously undescribed in the human population are identified and characterized, reports regarding these details will be written and published but such timelines are impossible to predict. Also, as new information on previously identified genes is gathered generated, additional reports will be issued through scientific publications. As long as funding is available, the work will proceed in a rolling, ongoing timeline.

Biospecimen Retention:   Samples With DNA
Following specimens may be submitted: saliva, blood, discarded tissue

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Ages Eligible for Study:   1 Day and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Individuals diagnosed with strabismus, congenital ocular motility disorders, cranial nerve dysfunction, brainstem disorders and other associated anomalies, as well as their similarly affected or unaffected family members. Unaffected individuals are enrolled only if a relative is diagnosed with one of these conditions at least one affected family members is enrolled.

Inclusion Criteria:

  • The Engle Lab is very interested in enrolling individuals with congenital conditions related to eye movement, cranial nerve and brainstem-based dysfunction, often broadly referred to as congenital cranial dysinnervation disorders (CCDDs).

Exclusion Criteria:

  • Individuals with cranial nerve disorders associated with known disorders, such as Saethre-Chotzen associated with established genetic mutations, or acquired conditions including trauma, stroke, tumor or spinal cord injuries.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03059420

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Contact: Brenda J Barry, MS 617-919-2168 brenda.barry2@childrens.harvard.edu
Contact: Engle Admin 617-919-4030 engle.admin@childrens.harvard.edu

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United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children's Hospital
Howard Hughes Medical Institute
National Eye Institute (NEI)
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Principal Investigator: Elizabeth Engle, MD Boston Children's Hospital

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Responsible Party: Elizabeth Engle, Investigator, Howard Hughes Medical Institute; Professor of Neurology and Ophthalmology, Harvard Medical School, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT03059420    
Other Study ID Numbers: 05-03-036R
R01EY015298 ( U.S. NIH Grant/Contract )
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: September 26, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Elizabeth Engle, Boston Children's Hospital:
CFEOM (Congenital Fibrosis of Extraocular Muscles)
CCDD (Congenital Cranial Dysinnervation Disorders)
DRS (Duane Retraction Syndrome)
DRRS (Duane Radial Ray Syndrome)
MGJWS (Marcus Gunn Jaw Winking Syndrome)
HGP (Horizontal Gaze Palsy)
HGPPS (Horizontal Gaze Palsy with Progressive Scoliosis)
Additional relevant MeSH terms:
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Facial Paralysis
Mobius Syndrome
Peripheral Nervous System Diseases
Ocular Motility Disorders
Duane Retraction Syndrome
Oculomotor Nerve Diseases
Trochlear Nerve Diseases
Abducens Nerve Diseases
Accessory Nerve Diseases
Hypoglossal Nerve Diseases
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Disease Attributes
Spinal Curvatures
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Congenital Abnormalities
Cranial Nerve Diseases