Centronuclear Myopathy

Centronuclear myopathy is a group of congenital myopathies with centrally placed nuclei in muscle fibres. Main types are X-linked myotubular myopathy (MTM1), autosomal dominant (DNM2, BIN1) and recessive (BIN1, RYR1, TTN). Prevalence is about 1 in 50,000 live births.

Pathophysiology. Defects of membrane remodelling (myotubularin, dynamin 2, amphiphysin 2) disrupt excitation contraction coupling and organelle positioning.

X-linked myotubular myopathy: severe neonatal hypotonia and respiratory failure in boys, ophthalmoplegia, ptosis, long fingers and macrocephaly, with liver disease (peliosis hepatis) and a high infant mortality. Dominant DNM2: mild to moderate weakness from childhood or adulthood with ptosis, ophthalmoparesis and distal weakness. Recessive forms: infantile or childhood onset. Female carriers of MTM1 may have mild weakness.

Red flags.

• Neonatal respiratory failure.
• Bleeding or abnormal liver tests in myotubular myopathy.

Muscle biopsy shows central nuclei in a large proportion of fibres with radial arrangement of sarcoplasmic strands. Creatine kinase is normal or mildly raised. Muscle MRI shows pattern of involvement. Genetic testing (panel or exome) confirms the diagnosis. Assess respiratory, cardiac, swallowing and liver function.

Differential diagnosis.

• Other congenital myopathies, myotonic dystrophy and congenital muscular dystrophy.
• Spinal muscular atrophy and Pompe disease.
• Centronuclear changes in regenerating muscle.

Supportive care, with specialist centres.

Respiratory care. Early ventilation (non-invasive or tracheostomy) for neonatal disease after discussion with parents, cough assist, and nocturnal ventilation with hypoventilation.

Feeding. Gastrostomy and dietitian input.

Liver and bleeding. In X-linked myotubular myopathy, monitor liver function and clotting, and avoid liver biopsy, owing to bleeding risk.

Physical care. Physiotherapy, orthoses, scoliosis care, ophthalmology for ptosis and strabismus, and dental care.

Education and support. Educational and social support, palliative care for severe disease.

Genetic therapy. Gene therapy for X-linked myotubular myopathy has been studied, with serious hepatic complications, and is not routinely available.

Monitoring. Respiratory function, liver tests, growth and scoliosis.

Referral and escalation. Refer to paediatric neuromuscular services and genetics.

Special groups. Genetic counselling and prenatal diagnosis are offered to carrier women.