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.
ASJC Scopus subject areas
- Clinical Neurology