To report novel mutation in desmin gene causing desmin myopathy.

Normal desmin (chief intermediate myofilament) and associated filaments are integral to maintain structural integrity of actin filaments during repeated skeletal or cardiac muscle contraction. Disruption of the filamentous network by the mutant desmin impairs the force generated within the contractile filaments and eventually cause skeletal or cardiac myopathy.

Case report

A 23-year-old female was seen in multidisciplinary clinic for progressive weakness in lower>upper extremities (Medical Research Council grading 4/5), dysphagia over the past few years. Family history was unrevealing for any history of progressive muscle weakness or unexplained respiratory failure or cardiac failure. Her past medical history is also significant for recurrent exertional dyspnea with recent hospitalization with cardiology for intravenous diuresis. She underwent transthoracic echocardiography and right heart catheterization which confirmed patient’s NYHA class II, stage C heart failure with preserved ejection fraction as secondary to restrictive cardiomyopathy. EMG/NCS showed a myopathic pattern. A right quadriceps biopsy demonstrated a dystrophic pattern associated with desmin-positive intra-cytoplasmatic aggregates, myofibrillar architecture. She underwent next generation genome sequencing and was found to have a novel DES c.1217G>T (p.Arg406Leu) variant in the highly conserved coil region of desmin gene.

This report is about a novel DES c.1217G>T (p.Arg406Leu) in the highly conserved coil region of desmin gene with a unique phenotype of limb-girdle pattern of muscle weakness and restrictive cardiomyopathy.