Severe X-linked Centronuclear (Myotubular) Myopathy

Cases with neonatal onset and severe respiratory insuf­ficiency have been identified with an X-linked reces­sive mode of inheritance. The gene for this disorder codes for myotubularin (MTM1), and has been linked to chromosome Xq27.3-q28.

Patients present with severe generalized hypoto­nia, associated muscle weakness, swallowing diffi­culty, and respiratory insufficiency. They often become ventilator-dependent at birth. If they are able to be weaned from the ventilator, subsequent death due to pulmonary complications is not uncommon. Mean age of death is 5 months, but some children survive for many years with mechanical ventilation. Aspiration pneumonias are common. Additional clinical features include congenital contractures, facial weakness with an elongated expressionless face, tent-shaped mouth, high arched palate, weakness of the external ocular muscles, and long digits. Progressive kyphoscolio­sis is common. Systemic features in some survivors >1 year of age include pyloric stenosis, spherocyto­sis, gallstones, renal stones or calcinosis, a vitamin K-responsive bleeding diathesis, rapid linear skeletal growth, advanced bone age, and hepatic dysfunction. Electromyography shows many fibrillations and posi­tive sharp waves.