Congenital Myopathies

ByMichael Rubin, MDCM, New York Presbyterian Hospital-Cornell Medical Center
Reviewed/Revised Jan 2024
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Congenital myopathy is a term sometimes applied to hundreds of distinct neuromuscular disorders that may be present at birth, but it is usually reserved for a group of rare, inherited, primary muscle disorders that cause hypotonia and weakness at birth or during the neonatal period and, in some cases, delayed motor development later in childhood. Diagnosis is clinical and is confirmed by muscle biopsy and sometimes MRI of the muscles. Treatment is supportive and includes physical therapy.

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually present from birth, with a static or slowly progressive clinical course. Although muscular dystrophies are also genetic disorders causing muscle weakness, they differ from congenital myopathies in age of onset, distribution of affected muscles, and the presence of characteristic dystrophic changes (eg, muscle fiber necrosis and regeneration) not present in biopsy specimens from congenital myopathies.

The 3 most common types of congenital myopathy, in order, are

  • Central core and multiminicore myopathies (core myopathies)

  • Centronuclear myopathy

  • Nemaline myopathy

The types are distinguished primarily by their histologic features, symptoms, and prognosis.

Diagnosis of congenital myopathies is suggested by characteristic clinical findings and is confirmed by muscle biopsy and sometimes MRI of muscles. The genetic variants responsible for many of the different forms of congenital myopathy have been identified, and DNA testing is sometimes done depending on the results of clinical evaluation and other tests.

Treatment of congenital myopathy is supportive and includes physical therapy, which may help preserve function.

Central Core Myopathy and Multiminicore Myopathy (Core Myopathies)

Central core myopathy and multiminicore myopathy (core myopathies) are the most common forms of congenital myopathy and are most commonly associated with RYR1 mutations. Inheritance is usually autosomal dominant, but recessive and sporadic forms exist.

Core myopathies are characterized by regions (cores) on muscle biopsy specimens in which oxidative enzyme staining is absent; regions may be peripheral or central, focal, multiple, or extensive. Central core myopathy was the first congenital myopathy to be identified.

Most affected patients develop hypotonia and mild proximal muscle weakness as neonates, but sometimes symptoms of core myopathy do not manifest until adulthood. Many also have facial weakness. Weakness is nonprogressive, and life expectancy is normal, but some patients are severely affected and require a wheelchair. The gene mutation associated with central core myopathy is also associated with increased susceptibility to malignant hyperthermia.

Centronuclear Myopathy

Centronuclear myopathy is characterized by an abundance of central nuclei on muscle biopsy. This myopathy may be X-linked, autosomal dominant, or autosomal recessive, but most genes implicated encode membrane-trafficking proteins.

X-linked forms are the most common and most severe, and most affected children do not survive beyond the first year of life.

Autosomal dominant forms typically manifest in adolescence or adulthood with exercise-induced myalgia, bifacial weakness, ptosis, and external ophthalmoplegia.

Nemaline Myopathy

This myopathy, one of the more common congenital myopathies, can be autosomal dominant or autosomal recessive. Causative mutations have been identified in 10 genes and all are related to the production of thin-filament proteins.

Nemaline myopathy may be severe, moderate, or mild. Severe disease may cause weakness of respiratory muscles and respiratory failure. Moderate disease causes progressive weakness in muscles of the face, neck, trunk, and feet, but life expectancy may be nearly normal. Mild disease is nonprogressive, and life expectancy is normal.

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