Clinical Trial: Study on Moebius Syndrome and Other Congenital Facial Weakness Disorders

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Study on Moebius Syndrome and Other Congenital Facial Weakness Disorders

Brief Summary:

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.

  Detailed Summary: This is a natural history study with a cross-sectional design of Moebius syndrome (MIM 157900), a heterogeneous developmental disorder defined as a congenital, non-progressive facial weakness with limited abduction of one or both eyes, often associated with additional features such as other cranial nerve dysfunction, craniofacial, skeletal and limb deformities, as well as intellectual or behavioral impairments. In this study we will attempt to characterize the clinical phenotype of Moebius and associated congenital facial weakness syndromes, collect thorough information on possible prenatal environmental exposures and use genetic studies, including whole exome sequencing, on DNA from patients and family members of patients to identify disease-causing genes. We will also conduct brain magnetic resonance- and diffusion tensor imaging- studies in these patients in order to explore brainstem and cranial nerve structure and associated white matter tract anomalies. Through this combined clinical, molecular and imaging approach, we anticipate that phenotype-genotype correlations will be revealed. These results will lead to new insights into the clinical definition of these conditions, molecular pathways, and potential networks involved in the pathogenesis of facial weakness and associated multisystem dysmorphogenesis. Our population will consist of patients, ages 2 to 80 years, inclusive of any gender, race, or ethnic group, with congenital facial palsy, isolated or combined with other congenital anomalies, and their families. We will recruit approximately 24 probands each year of the first three-years of the study, ages 2 to 80 years, inclusive of any gender, race, or ethnic group, and their parents and unaffected family members for a total of 72 patients/families. In most cases, patients will be referred through the Moebius Syndrome Foundation, a patient organization with a current membership of 2000 people in its database, 1400 of whom have been diagnosed with Moebius s
  Sponsor: National Human Genome Research Institute (NHGRI)
  

  Current Primary Outcome: Characterize the phenotype of Moebius syndrome and other congenital facial weakness disorders to determine the prevalence of associated malformations and inform subsequent genetic studies. [ Time Frame: 3 years ]
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome: Obtain imaging studies to explore cranial nerve structure and associated brain/brainstem and white matter tract anomalies and associate with the neurocognitive and behavioral phenotype of the patients. [ Time Frame: 3 years ]
  
  

  Original Secondary Outcome: Same as current
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: February 4, 2014
  Date Started: January 27, 2014
  Date Completion: September 4, 2017
  Last Updated: May 5, 2017
  Last Verified: December 28, 2013