Moebius Syndrome Research Opportunities Bryn D Webb MD

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

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

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, Mc. Carrell V, Neurology Reviews, 2019.

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%)

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)

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 (U 01 HD 079068) from Jan 2014 - Dec 2018 ▶ Multi-center collaboration continues

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

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Whole Exome Sequencing

Known Genetic Etiologies of Facial Weakness Conditions ▶ Hereditary Congenital Facial Paresis (HOXB 1) Webb et al, AJHG, 2012. ▶ Congenital fibrosis of extraocular muscles, 3 A (TUBB 3) Chew et al, Brain, 2013.

Known Genetic Etiologies of Facial Weakness Conditions Cont’d. ▶ Carey Fineman Ziter syndrome (Moebius plus Pierre Robin) (MYMK) Di. Gioia et al, Nat Commun, 2017. ▶ Native American Myopathy (STAC 3) Telegrafi, Webb et al, AJMG A, 2018.

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

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. : 212. 241. 1481 E-mail: Bryn. webb@mssm. edu