Dystrophin-Deficient Cardiomyopathy Due to a Novel Hemizygous DMD Indel Variant.

BACKGROUND

Variants of dystrophin can lead to diverse phenotypes, ranging from isolated cardiomyopathy to aggressive Duchenne muscular dystrophy with progressive skeletal muscle weakness.

CASE SUMMARY: We present a case of dystrophin-deficient cardiomyopathy in a 36-year-old man who presented in cardiogenic shock due to severe dilated cardiomyopathy requiring a bridge-to-transplant left ventricular assist device Genetic testing identified a DMD c.4857_4859del variant of uncertain significance. After heart transplantation, immunohistochemistry of the explanted heart revealed markedly reduced dystrophin staining, suggesting that the variant is disease-causing. Cascade testing identified multiple family members who were affected.

DISCUSSION: This case report underscores the importance of synthesizing the clinical phenotype with functional testing to classify cardiomyopathy gene variants accurately.

TAKE-HOME MESSAGE: Periodic review of variants of uncertain significance is critical to enable early diagnosis, treatment, and family screening.