G.O.6 Autosomal recessive desminopathy with desmin-null mutations presenting in childhood

Abstract

Abstract Desminopathies are intermediate filament disorders with a mainly dominant autosomal inheritance pattern, characterized by skeletal myopathy and/or cardiomyopathy with average onset in the 3rd decade. The clinical phenotype caused by desmin mutations is described as a myofibrillar myopathy (MFM). This term refers to a group of genetically heterogeneous neuromuscular disorders that share histopathological features of cytoplasmic aggregates of multiple proteins, including desmin, αB-crystallin and myotilin on muscle biopsy. We report on two siblings from healthy, non-consanguineous parents presenting with progressive generalized proximal more than distal muscle weakness in legs and arms from the age of 3 years, facial weakness and ptosis, reduced upward gaze, scapular winging, ankle contractures, mild calf hypertrophy, and swallowing difficulties. No cardiac involvement was detected so far. Creatine kinase levels were raised up to 800 and 1000 IU/L. A muscle MRI of the thigh showed more severe involvement of the posterior compartment with relative sparing of the sartorius and gracilis muscles. Muscle histopathology showed myopathic features with atrophic fibers, nuclear bags, internal nuclei and type 1 fibre predominance with remarkably complete absence of desmin labelling which was confirmed by Western blot. Mutation analysis revealed two compound heterozygous mutations in exon 1 of desmin gene resulting in premature stop codons. This novel clinical phenotype linked to autosomal recessive desminopathy widens the clinical spectrum of this class of disease.