Study on Moebius Syndrome and Congenital Facial Weakness Disorders
Condition: Brain Disorders; Birth Defects; Craniofacial Differences
MeSH terms: Mobius Syndrome; Brain Diseases; Congenital Abnormalities; Asthenia
Study type: Observational

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.

        -  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.
    

Detailed description: 
      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 continue to recruit approximately 24 probands each year, 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 syndrome. Outcome measures will
      include the results from a battery of clinical evaluations, including ophthalmology,
      audiology, neurology, psychiatry, and rehabilitative medicine. Patients will also undergo
      neurocognitive and autism screening assessments, electromyography/nerve conduction, and blink
      reflex studies. Imaging and genetic studies will provide the most robust data for analysis in
      this study. A skin biopsy may be performed on some patients in order to culture fibroblasts
      for additional biochemical, cell biological, and molecular analyses.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects with Moebius or related syndromes and their family members and healthy volunteers.
      
Keywords: Congenital Facial Weakness; Moebius; Cranial Nerve; Whole Exome Sequencing; Natural History