Poster 55

by in  Poster Session 1

COMMAD: A Novel Syndrome Caused by Biallelic Mutation of the MITF Gene

Brian P. Brooks; Dina J. Zand; Robert B. Hufnagel; Ruchi Sharma; Yuri V. Sergeev; David M. Gamm; Kapil Bharti;Aman George
National Eye Institute, Children’s National Medical Center and University of Wisconsin
Bethesda, MD; Washington, DC; Madison, WI

 

Introduction: Waardenburg syndrome, type2a (WS2a), is caused by mutations in the basic helix-loop-helix zipper gene, MITF, and often includes prominent ophthalmic features. Biallelic mutations in MITF have recently been found to cause COMMAD (coloboma, osteopetrosis, macrocephaly, microphthalmia, albinism and deafness) syndrome (1).

Methods: Deep clinical phenotyping, DNA sequencing, in vitro molecular characterization

Results: Two unrelated probands exhibit the COMMAD phenotype, reminiscent of the mi/mi mouse model. DNA binding, nuclear localization, & transactivation were variably affected by different mutations. Examination of WS2a parents revealed variable decreased best-corrected visual acuity, anterior segment dysgenesis, and foveal hypoplasia.

Discussion: Visual impairment due to foveal hypoplasia in WS2a is not widely recognized. Neither set of WS2a parents was aware of their underlying diagnosis or their risk for having a profoundly-affected deaf-blind child.

Conclusion: COMMAD represents a novel constellation of signs and symptoms, leading to|profound sensory system impairment. Recognition of WS2a and COMMAD syndrome by pediatric ophthalmologists is critical for genetic counseling and ophthalmic and medical care.

References: 1. George A et al. Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness [Internet]. Am. J. Hum. Genet. 2016;99(6):1388-1394.

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