DES c.1360C>T: A Rare Desmin Variant Causing Early Distal Myopathy and Cardiomyopathy

Desmin-related myopathies are characterized by progressive, distal skeletal muscle weakness, cardiomyopathy, and cardiac conduction disease caused by mutations of Desmin. A 43-year-old man with a history of heart transplant due to heart failure associated with restrictive cardiomyopathy, presented with slowly progressive distal muscle weakness in all four extremities for five years. On examination, predominantly distal quadriparesis and atrophy were noted, worse on the upper limbs, and reduced reflexes with normal sensation. His electromyographic studies were suggestive of subacute moderate motor axonal polyneuropathy secondary to the transplant immunosuppression. The patient's father died at 33 years due to heart failure, and his 37-year-old brother, who also had a heart transplant, had noticed the development of muscle atrophy. Another electroneuromyography performed on our index patient confirmed features consistent with a distal myopathy. A genetic panel for distal myopathies with cardiac involvement identified the pathological desmin gene mutation DES (NM_001927.4) - c.1360C>T; (p.(Arg454Trp)). Desmin-related myopathies are a diagnostic challenge. The beginning of neurological symptoms several years after the cardiac symptoms and the use of immunosuppressive agents may have contributed to the early misdiagnosis.