Duchenne Muscular Dystrophy and Early onset Hypertrophic Cardiomyopathy Caused by Co-occurring Mutations in Dystrophin and Hypertrophic Cardiomyopathy-Associated Genes

נגה ארואס ¹ Liam Aspit ^2,3 Hana Krimko ¹ Yoram Etzion ⁴ Ruti Parvari ^2,3 Aviva Levitas ¹

¹Pediatric Cardiology Unit, Soroka Medical Center, ישראל
²The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben Gurion University, ישראל
³The National Institute for Biotechnology in the Negev, Ben Gurion University, ישראל
⁴Department of Physiology and Cell Biology, Faculty of Health Sciences and Regenerative Medicine and Stem Cell Research Center, Ben Gurion University, ישראל

Duchenne muscular dystrophy (DMD) is a genetic progressive muscular disorder caused by mutations in dystrophin. The common genetic mutations found in DMD patients are deletions of exons 51-54 of dystrophin. Cardiac involvement may first be clinically evident at age 10 years and increases in incidence with age.

We present a case of a male patient diagnosed at age 18 months with a rare phenotype of DMD in conjunction with early-onset Hypertrophic cardiomyopathy (HCM). The cause for HCM was verified by whole-exome sequencing. Novel missense variations in two genes: MAP2K5, inherited from his healthy mother and ACTN2 inherited from his healthy father, or de-novo. Their combination could be causing HCM.

This is the second published case of a patient diagnosed at a relatively young age with DMD and HCM, presenting novel variations in genes previously associated with HCM. This study demonstrates the need for genetic diagnosis for elucidating the underlying pathology of HCM.