- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02055248
Study on Moebius Syndrome and Congenital Facial Weakness Disorders
Study on Moebius Syndrome and Other Congenital Facial Weakness Disorders
Background:
- Moebius syndrome limits the ability to make facial expressions like smile, frown or blink - and move the eyes laterally. It can also cause speech, swallowing or breathing difficulties and affect parts of the body, such as the limbs, jaw, muscles, or the heart. Some individuals with Moebius can have intellectual impairment or behavior problems. Researchers want to study the clinical features of individuals with Moebius or related disorders and explore the genetic and/or environmental causes of these conditions.
Objective:
- To learn more about the genetics and clinical characteristics of Moebius syndrome and other Congenital Facial Weakness disorders.
Eligibility:
- People ages 2 to 80 years with congenital facial weakness, isolated or combined with other congenital anomalies, and their family members.
Design:
- Participants with Moebius syndrome or other congenital facial weakness disorder will be evaluated at the NIH Clinical Research Center over 3 to 5 days and undergo the following procedures:
- Medical and family history and physical examination, including body measurements and vital signs.
- Blood or saliva will be collected for genetic tests and to evaluate liver, kidney, heart and hormonal
functions.
- Eye examination, including having a video taken of their eyes moving.
- Hearing evaluation.
- Speech and language assessment, including swallowing studies.
- Dental exam.
- Detailed neurological evaluation, including electromyogram/nerve conduction and blink reflex study.
- Rehabilitation medicine evaluation, including muscle and tongue strength testing and assessment of balance.
- Neurocognitive and behavioral testing and questionnaires to assess quality of life and copying mechanisms.
- Imaging studies of their head, by magnetic resonance and diffusion tensor imaging -MRI/DTI. Participants
will lie on a table that slides into a metal cylinder that takes images of internal body structures using
magnets. Child participants may be sedated.
- Some adults may have additional X-rays of their head or limbs, if there are abnormal findings.
- Medical photographs of the face and affected body parts may be taken.
- Other specialized tests or consultations, as indicated.
- Participants can choose to have a skin biopsy taken.
- A follow-up visit will be offered to participants for review of genetic test findings and possibly additional clinical tests, as indicated.
Family members of the patients will have a medical and family history and physical examination. Blood or saliva will be obtained for genetic studies.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
INCLUSION CRITERIA:
- Subject is 2-80 years, any gender, race or ethnic group, inclusive.
- Subject has a diagnosis of congenital facial palsy, isolated or combined with other congenital anomalies, based on MPIs review of prior medical records and interview with patient and/or patient physicians.
- Subject is a family member of a patient with a diagnosis of congenital facial palsy, isolated or combined with other congenital anomalies.
- Subject has the ability to travel to the NIH Clinical Center for admissions.
- Subject or subject s legal guardian is able to provide written informed consent.
EXCLUSION CRITERIA:
- Subject has severe respiratory difficulties (i.e., requiring a tracheostomy or other assistive device to maintain respiration) or other disease manifestation that would interfere with the ability to comply with the requirements of this protocol and/or pose a severe anesthesia risk.
- Subject has a psychiatric illness or neurological disease that would interfere with the ability to comply with the requirements of this protocol. This includes, but is not limited to, uncontrolled/untreated psychotic depression, bipolar disorder, schizophrenia, substance abuse or dependence, antisocial personality disorder, or panic disorder.
- Subject shows evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, or gastrointestinal disease, or has a condition that requires immediate surgical intervention.
- Subject is pregnant during the study.
- Subject or subject s legal guardian is unable or unwilling to provide consent or assent.
- The principal investigator may decline to enroll a patient for other reasons.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
---|
Subjects with Moebius or related syndromes and their family me
Subjects with Moebius or related syndromes and their family members and healthy volunteers.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Employ genetic studies to study the molecular bases underlying congenital facial weakness syndromes.
Time Frame: One visit only
|
Employ genetic studies, including comparative genomic hybridization, candidate gene testing and/or whole exome and genome sequencing to study the molecular bases underlying these syndromes.
Our hypothesis is that disease-causing mutations will be present in the proteincoding regions of the genome, as germline or somatic mutations.
In the future whole genome sequencing may be considered.
|
One visit only
|
Characterize the phenotype of patients with typical Moebius syndrome
Time Frame: One visit only
|
To characterize the phenotype of patients with typical Moebius syndrome, defined as uni- or bilateral facial and uni- or bilateral abducens nerve palsy and patients with atypical Moebius-like phenotypes that include facial weakness, including Moebius-Poland, Moebius-Robin or Moebius-Kallmann syndromes, Carey-Fineman-Ziter syndrome, Hereditary Congenital Facial Paresis (HCFP), oculoauriculovertebral dysplasia (Goldenhar syndrome), among others, and determine the prevalence of associated malformations.
Our primary hypothesis is that oculomotor, neuromuscular, skeletal or imaging endophenotypes will help categorize the various groups more accurately and inform subsequent genetic studies.
|
One visit only
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Obtain brain-imaging studies including DTI/tractography
Time Frame: one time only
|
Obtain brain-imaging studies including DTI/tractography in a large cohort of patients with congenital malformations associated with facial weakness to explore anomalies in brain and brainstem structure and associated white matter anomalies and fiber tract connectivity, together with a careful delineation of patients' neurocognitive andbehavioral phenotype.
Results from this distinct developmental disorder will be compared to data from normal children and children with non-syndromic autism.
|
one time only
|
Study the neurocognitive, behavioral, and quality of life outcomes of individuals with congenital facial weakness
Time Frame: one time only
|
Study the neurocognitive, behavioral, and quality of life outcomes of individuals with these syndromes, and provide proper genetic counseling about management, prognosis, and recurrence risk to affected families
|
one time only
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Eirini Manoli, M.D., National Human Genome Research Institute (NHGRI)
Publications and helpful links
General Publications
- Webb BD, Shaaban S, Gaspar H, Cunha LF, Schubert CR, Hao K, Robson CD, Chan WM, Andrews C, MacKinnon S, Oystreck DT, Hunter DG, Iacovelli AJ, Ye X, Camminady A, Engle EC, Jabs EW. HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/- mice. Am J Hum Genet. 2012 Jul 13;91(1):171-9. doi: 10.1016/j.ajhg.2012.05.018. Epub 2012 Jul 5.
- Di Gioia SA, Connors S, Matsunami N, Cannavino J, Rose MF, Gilette NM, Artoni P, de Macena Sobreira NL, Chan WM, Webb BD, Robson CD, Cheng L, Van Ryzin C, Ramirez-Martinez A, Mohassel P, Leppert M, Scholand MB, Grunseich C, Ferreira CR, Hartman T, Hayes IM, Morgan T, Markie DM, Fagiolini M, Swift A, Chines PS, Speck-Martins CE, Collins FS, Jabs EW, Bonnemann CG, Olson EN; Moebius Syndrome Research Consortium; Carey JC, Robertson SP, Manoli I, Engle EC. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017 Jul 6;8:16077. doi: 10.1038/ncomms16077.
- Telegrafi A, Webb BD, Robbins SM, Speck-Martins CE, FitzPatrick D, Fleming L, Redett R, Dufke A, Houge G, van Harssel JJT, Verloes A, Robles A, Manoli I, Engle EC; Moebius Syndrome Research Consortium; Jabs EW, Valle D, Carey J, Hoover-Fong JE, Sobreira NLM. Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome. Am J Med Genet A. 2017 Oct;173(10):2763-2771. doi: 10.1002/ajmg.a.38375. Epub 2017 Aug 4.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Eye Diseases
- Infant, Newborn, Diseases
- Stomatognathic Diseases
- Mouth Diseases
- Cranial Nerve Diseases
- Ocular Motility Disorders
- Abnormalities, Multiple
- Facial Nerve Diseases
- Congenital Cranial Dysinnervation Disorders
- Oculomotor Nerve Diseases
- Congenital Abnormalities
- Brain Diseases
- Asthenia
- Mobius Syndrome
Other Study ID Numbers
- 140055
- 14-HG-0055
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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