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  • Updated 07.07.2021
  • Released 11.30.1996
  • Expires For CME 07.07.2024

Desmin body myofibrillar myopathy

Introduction

Overview

Myofibrillar myopathies refer to a heterogeneous group of genetic disorders associated with disintegration of myofibrils and accumulation of Z-disc related proteins, with variable age of onset and disease progression. Typically, patients present with lower limb muscle weakness, which slowly spreads to involve the upper limbs, truncal, neck-flexor, facial, bulbar, and respiratory muscles. Distribution of the weakness may be distal or both proximal and distal. Skeletal myopathy may be combined with or preceded by cardiomyopathy, conduction blocks, and arrhythmias that can result in sudden death. Respiratory muscle weakness can also be a major complication in some patients. In this updated article, the author highlights advances in the diagnosis and management of myofibrillar myopathies.

Key points

• Myofibrillar myopathies are a subgroup of hereditary protein aggregate myopathies.

• Muscle biopsy reveals characteristic amorphous or granular material, with focal areas of myofibrillar disintegration, reduced oxidative enzyme activity, and vacuolar changes.

• The clinical phenotype is highly variable; most commonly it presents as a distal myopathy involving the hands and feet, with progressive muscle weakness, respiratory dysfunction, and cardiomyopathy.


• Treatment remains primarily supportive; those with significant cardiac complications may require pacemaker implantation or cardiac transplant.

Historical note and terminology

Myofibrillar myopathies refer to a heterogeneous group of rare inherited primary chronic noninflammatory myopathies characterized by abnormal accumulation of cytoplasmic inclusion bodies and myofibrillar disarray in skeletal or cardiac muscles (39; 05; 34). The disease was originally described more than 30 years ago based on common muscle histopathological features (38). The onset usually occurs in adult life (between the second and fourth decade) but may be congenital or present in early childhood. A combination of distal and proximal weakness, cardiomyopathy, peripheral neuropathy, and autosomal dominant inheritance should suggest this disorder (74). However, these symptoms may be sporadic, and autosomal recessive or X-linked inheritance has also been described (33; 103).

The first description of cytoplasmic body as a structural anomaly of the Z-disc was in 1969 (68). Cytoplasmic bodies occur in a number of unrelated neuromuscular disorders, but their relationship to desmin-related neuromuscular diseases was only recognized in the 1980s (28; 116; 81).

A report of a sporadic adult-onset myopathy describing spheroid inclusions on the basis of the ultrastructural findings and the formation of the inclusions in muscle fibers was postulated (75). Other early reports of sporadic cases include postmortem findings of cytoplasmic bodies and myofibrillar aggregates (56; 53). Autosomal dominant inheritance was described in 4 successive generations with a benign proximal myopathy of adolescent onset with spheroid bodies (41) or granulofilamentous inclusions (30). Similarly, a late-onset myopathy showed myofibrillar inclusions in all 3 symptomatic and in 4 of the 7 asymptomatic family members (17). Intermediate filaments were identified in association with sarcoplasmic bodies in a severe progressive late-onset autosomal dominant distal myopathy, with patients becoming wheelchair-bound within 10 years (28). Sixteen patients representing 7 different pedigrees with an adult-onset limb-girdle myopathy (27) and 16 family members with a distal myopathy were described (50). A cardiomyopathy found in 3 brothers showed large proteinaceous inclusions in the cardiac muscle consisting of intermediate filaments (88) that were immunofluorescent desmin-positive (116). Desmin body myofibrillar myopathy was also found to be associated with a congenital form of myopathy with or without cardiomyopathy (42; 130). The cardiomyopathy could precede the myopathy (09; 43).

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