RESUMEN
BACKGROUND AND OBJECTIVES: We aimed to determine the genetic and clinical phenotypes of patients with desmin-related myopathy and long-term outcomes after cardiac transplantation. METHODS: We performed a retrospective review of cardiac and neurologic manifestations of patients with genetically confirmed desmin-related myopathy (January 1, 1999-January 1, 2020). RESULTS: Twenty-five patients in 20 different families were recognized. Median age at onset of symptoms was 20 (range 4-50) years; median follow-up time was 36 (range 1-156) months. Twelve patients initially presented with skeletal muscle involvement, and 13 presented with cardiac disease. Sixteen patients had both cardiac and skeletal muscle involvement. Clinically muscle weakness distribution was distal (n = 11), proximal (n = 4), or both (n = 7) in 22 patients. Skeletal muscle biopsy from patients with missense and splice site variants (n = 12) showed abnormal fibers containing amorphous material in Gomori trichrome-stained sections. Patients with cardiac involvement had atrioventricular conduction abnormalities or cardiomyopathy. The most common ECG abnormality was complete atrioventricular block in 11 patients, all of whom required a permanent pacemaker at a median age of 25 (range 16-48) years. Sudden cardiac death resulting in implantable cardioverter-defibrillator (ICD) shocks or resuscitation was reported in 3 patients; a total of 5 patients had ICDs. Orthotopic cardiac transplantation was performed in 3 patients at 20, 35, and 39 years of age. DISCUSSION: Pathogenic variants in desmin can lead to varied neurologic and cardiac phenotypes beginning at a young age. Two-thirds of the patients have both neurologic and cardiac symptoms, usually starting in the third decade. Heart transplantation was tolerated with improved cardiac function and quality of life.