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Centronuclear myopathy (CNM) is an inherited neuromuscular disorder characterized by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy.
ORPHA:595Classification level: Group of disorders
- Prevalence: Unknown
- Inheritance: Autosomal dominant or Autosomal recessive or X-linked recessive
- Age of onset: Childhood, Neonatal, Infancy, Adolescent, Adult
- ICD-10: G71.2
- OMIM: -
- UMLS: C0175709
- MeSH: -
- GARD: 101
- MedDRA: -
The incidence of X-linked CNM is estimated at 2/50,000 male births but epidemiological data for the other forms are not currently available.
The clinical picture is highly variable. The X-linked form usually gives rise to a severe phenotype in males, with presentation at birth of marked weakness and hypotonia, external ophthalmoplegia, and respiratory failure. Signs of antenatal onset are reduced fetal movements, polyhydramnios and thinning of the ribs on chest radiographs. Birth asphyxia may occur. Affected infants are often macrosomic, with length above the 90th centile and a large head circumference. Testes are frequently undescended. Both autosomal-recessive (AR) and autosomal-dominant (AD) forms differ from the X-linked form with regard to the age at onset, severity, clinical characteristics and prognosis. In general, AD forms have a later onset and milder course than the X-linked form, and the AR form is intermediate in both respects.
Mutations in the myotubularin (MTM1) gene on chromosome Xq28 have been identified in the majority of patients with the X-linked recessive form, whilst the AD and AR forms have been associated with mutations in the dynamin 2 (DNM2) gene on chromosome 19p13.2 and the amphiphysin 2 (BIN1) gene on chromosome 2q14, respectively. Single cases with features of CNM have been associated with mutations in the skeletal muscle ryanodine receptor (RYR1) and the hJUMPY (MTMR14) genes.
Diagnosis is based on typical histopathological findings on muscle biopsy, in combination with suggestive clinical features. Muscle magnetic resonance imaging may complement clinical assessment and be informative for genetic testing in cases with equivocal features.
The main differential diagnoses include congenital myotonic dystrophy and other conditions with severe neonatal hypotonia.
Genetic counseling should be offered to all patients and families in whom a diagnosis of CNM has been made.
Management and treatment
Management of CNM is mainly supportive, based on a multidisciplinary approach.
Whereas the X-linked form due to MTM1 mutations is often fatal in infancy, dominant forms due to DNM2 mutations and some cases of the recessive BIN1 -related form appear to be associated with a globally more favorable prognosis.
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