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Autosomal dominant centronuclear myopathy
Autosomal dominant centronuclear myopathy (AD-CNM) is an inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy.
The exact prevalence remains unknown.
Most commonly, the age of onset is in adolescence, although earlier presentations in infancy or childhood have been reported. Muscle weakness of variable severity is the major clinical manifestation. Distal muscle involvement, particularly in the lower limb, may precede more proximal weakness; the latter finding corresponds to a sequential pattern of involvement on muscle magnetic resonance imaging (MRI) with early involvement of the ankle plantarflexors, namely the medial gastrocnemius, followed by signal changes in the posterior and, eventually, anterior compartment of the thighs. Marked ocular involvement including ptosis and ophthalmoparesis are common, whilst contractures other than those affecting the Achilles tendon and/or long finger flexors are rare. Cardiorespiratory function has been reported as normal in most cases. Patients with early onset may improve in terms of muscle strength but may develop restrictive respiratory impairment over time. Neuropathic signs (absence of tendon reflexes on neurological examination and fibrillations or reduction of the compound muscle action potential on electrophysiological examination) may be present.
Mutations in the dynamin 2 (DNM2) gene on chromosome 19p13.2 are responsible for AD-CNM. DNM2 mutations also cause Charcot-Marie-Tooth disease Type 2B (CMT2B) (see this term).
Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features. Muscle MRI may aid the diagnosis which is confirmed on genetic testing.
The main differential diagnoses include other congenital myopathies with predominant distal involvement, myotonic dystrophy and, if facial involvement is prominent, fascio-scapulo-humeral dystrophy (FSH) (see these terms).
Genetic counseling should be offered to all patients and families.
Management and treatment
There is no curative treatment currently available. Management is supportive and based on a multidisciplinary approach.
The disease has usually a slowly progressive course with potential loss of independent ambulation after the sixth decade.