Expanding Spectrum of Desmin-Related Myopathy, Long-term Follow-up, and Cardiac Transplantation.

OBJECTIVE: We aimed to determine the genetic and clinical phenotypes of desmin-related myopathy patients and long-term outcomes after cardiac transplant.

METHODS: Retrospective review of cardiac and neurological manifestations of genetically confirmed desmin-related myopathy patients (Jan 1st , 1999-Jan 1st , 2020).

RESULTS: Twenty-five patients in 20 different families were recognized. Median age at onset of symptoms was 20 years (range: 4-50), median follow-up time of 36 months (range: 1-156). Twelve patients initially presented with skeletal muscle involvement and 13 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) of 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 AV block in 11 patients all of whom required a permanent pacemaker at a median age of 25 years (range: 16-48). Sudden cardiac death resulting in implantable cardioverter defibrillator (ICD) shocks or resuscitation were 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.

CONCLUSIONS: Pathogenic variants in desmin can lead to varied neurological 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 transplant was tolerated with improved cardiac function and quality of life.