Study on Moebius Syndrome and Congenital Facial Weakness Disorders

NCT02055248 | Completed

• 2 other identifiers: 14005514-HG-0055
• Study Type: observational
• Target: 207
• Locations: 1 country
• Sites: 1

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.
• 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.

Conditions

Brain Disorders; Birth Defects; Craniofacial Differences

Keywords

Congenital Facial Weakness; Moebius; Cranial Nerve; Whole Exome Sequencing; Natural History

Outcome Measures

Primary Outcomes (2)

• Employ genetic studies to study the molecular bases underlying congenital facial weakness syndromes.

  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

  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 Outcomes (2)

• Obtain brain-imaging studies including DTI/tractography

  one time only

• Study the neurocognitive, behavioral, and quality of life outcomes of individuals with congenital facial weakness

  one time only

Study Arms (1)

Subjects with Moebius or related syndromes and their family me

Subjects with Moebius or related syndromes and their family members and healthy volunteers.

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with Moebius or related syndromes and their family members and healthy volunteers.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): collaborator
• Boston Children's Hospital: collaborator
• National Human Genome Research Institute (NHGRI): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 28681861 BACKGROUND

• 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.

  PMID: 28777491 BACKGROUND

• 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.

  PMID: 22770981 BACKGROUND

• Japee S, Jordan J, Licht J, Lokey S; Moebius Syndrome Research Consortium; Chen G, Snow J, Jabs EW, Webb BD, Engle EC, Manoli I, Baker C, Ungerleider LG. Inability to move one's face dampens facial expression perception. Cortex. 2023 Dec;169:35-49. doi: 10.1016/j.cortex.2023.08.014. Epub 2023 Sep 30.

  PMID: 37852041 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Brain Diseases; Congenital Abnormalities

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Eirini Manoli, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2014
• First Posted: February 5, 2014
• Study Start: May 20, 2014
• Primary Completion: April 29, 2020
• Study Completion: April 29, 2020
• Last Updated: April 8, 2026

Record last verified: 2026-01-14

Locations

US (1)