Search for a rare disease
Other search option(s)
Autosomal recessive centronuclear myopathy
A rare autosomal recessive congenital myopathy characterized by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy including facial weakness, ocular abnormalities (ptosis and external ophthalmoplegia) and predominant proximal muscle weakness of variable severity with possible distal involvement.
ORPHA:169186Classification level: Disorder
The exact prevalence remains unknown.
The age of onset varies from birth to childhood. AR-CNM is characterized by facial weakness including severe involvement of the masticatory muscles, and ocular abnormalities such as ptosis and external ophthalmoplegia. Muscle weakness is observed with variable severity. It is usually prominently proximal, but there may be additional distal weakness and wasting in the lower limbs. Foot abnormalities are frequent and other skeletal deformities (including high arched palate and scoliosis) are common. Respiratory involvement may be severe. An associated cardiomyopathy has been documented in a few, genetically unresolved cases. Urinary incontinence may be an associated feature.
The disease is associated with mutations in BIN1 (2q14), encoding Myc box-dependent-interacting protein 1. AR- CNMs can be also related to biallelic mutation in RYR1 (19q13.2) , SPEG (2q35) and TTN (2q31.2) genes.
Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features. Genetic testing is required to confirm the diagnosis. Muscle MRI may be helpful to distinguish AR-CNM from other forms of CNM.
The main differential diagnoses include other congenital myopathies, myotonic dystrophy and, if facial involvement is prominent, facioscapulohumeral dystrophy.
Prenatal diagnosis is possible where the mutation has previously been identified in a family member.
The pattern of inheritance is autosomal recessive. The risk to siblings of inheriting the disease is 25%. Offspring of affected individuals are obligate carriers. Genetic counseling should be offered to all patients and their families.
Management and treatment
There is no curative treatment currently available. Management is supportive and based on a multidisciplinary approach.
In the absence of severe cardiorespiratory involvement, the prognosis appears favorable, with mild progressive proximal weakness.
Article for general public