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

Sponsor

Boston Children's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03059420

Collaborator

Howard Hughes Medical Institute (Other), National Eye Institute (NEI) (NIH)

20,000

Enrollment

Location

275

Anticipated Duration (Months)

72.7

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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.

Study Design

Study Type:

Observational

Anticipated 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 :

Feb 1, 2004

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jan 1, 2027

Outcome Measures

Primary Outcome Measures

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. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day and Older

Sexes Eligible for Study:

All

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Children's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

Boston Children's Hospital
Howard Hughes Medical Institute
National Eye Institute (NEI)

Investigators

Principal Investigator: Elizabeth Engle, MD, Boston Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

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

First Posted:

Feb 23, 2017

Last Update Posted:

Sep 10, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Elizabeth Engle, Investigator, Howard Hughes Medical Institute; Professor of Neurology and Ophthalmology, Harvard Medical School, Boston Children's Hospital

CFEOM (Congenital Fibrosis of Extraocular Muscles)

CCDD (Congenital Cranial Dysinnervation Disorders)

DRS (Duane Retraction Syndrome)

DRRS (Duane Radial Ray Syndrome)

Strabismus

MGJWS (Marcus Gunn Jaw Winking Syndrome)

HGP (Horizontal Gaze Palsy)

HGPPS (Horizontal Gaze Palsy with Progressive Scoliosis)

Moebius

Additional relevant MeSH terms:

Scoliosis

Facial Paralysis