1. Moebius Syndrome: Research Opportunities
Bryn D. Webb, MD, FACMG
Assistant Professor
Depts. of Genetics & Genomic Sciences and Pediatrics
Icahn School of Medicine at Mount Sinai
April 6, 2018

2. What is Moebius Syndrome?
Eponymously named for German neurologist Paul Julius Möbius, who reported features of the condition in 1888
Original description was provided by German ophthalmologist Dr. A. Von Graefe in 1880
Variability/disagreement in the literature regarding the precise definition of Moebius syndrome
Von Graefe
P.J. Möbius

3. Moebius Syndrome: Definition
In 2007, at a MSF research conference, Moebius syndrome was defined as congenital, non-progressive facial weakness with limited abduction of one or both eyes
Webb BD, McCarrell V, Neurology Reviews,

4. Moebius Syndrome: Associated Features
Affected persons may have additional symptoms including, but not limited to:
Other Cranial Nerve involvement
Strabismus
Hearing loss
Club foot
Limb reduction deficits
Other limb anomalies
Poland anomaly
Muscular hypotonia
Congenital heart disease
Developmental delay/ intellectual disability (~30%)
Autism (~25%)

5. Moebius Syndrome: Epidemiology and Etiology
Incidence is roughly 2 to 20 cases per million births
Occurs in all ethnicities
No gender bias (males and females affected similarly)
Most commonly a sporadic occurrence (usually one person in the family affected)

6. Moebius Syndrome Research Consortium
Formally initiated when applying for an NIH grant in 2013
Includes investigators from Mount Sinai, Boston Children’s Hospital, and the NIH
Also collaborations with outside investigators
Funded by NIH (U01 HD079068) from Jan Dec 2018
Multi-center collaboration continues

7. Objectives of Moebius Syndrome Research
Phenotyping
identify associated features and frequency
determine subtypes, if possible
Perform natural history study
Example: how do persons with Moebius syndrome do over time?
Identify etiologies (environmental, genetic)
Employ state of the art sequencing techniques (whole exome sequencing (WES), whole genome sequencing (WGS) to identify genetic changes that may cause Moebius syndrome or related facial weakness disorders

9. Whole Exome Sequencing

10. Known Genetic Etiologies of Facial Weakness Conditions
Hereditary Congenital Facial Paresis (HOXB1)
Congenital fibrosis of extraocular muscles, 3A (TUBB3)
Webb et al, AJHG, 2012.
Chew et al, Brain, 2013.

11. Known Genetic Etiologies of Facial Weakness Conditions Cont’d.
Carey Fineman Ziter syndrome (Moebius plus Pierre Robin) (MYMK)
Native American Myopathy (STAC3)
DiGioia et al, Nat Commun, 2017.
Telegrafi, Webb et al, AJMG A, 2018.

12. How To Participate Complete consent form Complete questionnaire
Also helpful to perform physical exam or share medical records
Provide saliva sample for isolation of DNA
Enrollment can be done today at the conference or can also be completed via phone & mail

13. E-mail: Bryn.webb@mssm.edu
Contact Information:
Bryn D. Webb, MD, FACMG
Assistant Professor
Dept. of Genetics & Genomics Sciences
Icahn Institute for Genomics & Multiscale Biology
Icahn School of Medicine at Mount Sinai
New York, NY, USA
Office tel.: