Severe congenital nemaline myopathy

Severe congenital nemaline myopathy (also known as severe neonatal nemaline myopathy) is the most serious form of nemaline myopathy, a group of inherited neuromuscular disorders characterized by the presence of rod-shaped structures called nemaline bodies (or nemaline rods) in skeletal muscle fibers. This severe form presents at birth or in the neonatal period with profound generalized muscle weakness (hypotonia), minimal or absent spontaneous movements, and severe respiratory insufficiency that typically requires immediate ventilatory support. Affected infants often have significant feeding difficulties requiring tube feeding, and many display a lack of antigravity limb movements. The disease primarily affects the skeletal muscular system, but secondary complications involve the respiratory and gastrointestinal systems. Key clinical features include severe diffuse weakness, absent or markedly reduced deep tendon reflexes, facial weakness, a thin and elongated face, high-arched palate, chest deformities, and joint contractures. Bulbar weakness contributes to swallowing difficulties and aspiration risk. Many affected infants also develop fractures due to osteopenia from immobility. The prognosis is generally poor, with many infants dying within the first year of life due to respiratory failure. Severe congenital nemaline myopathy can be caused by mutations in several genes involved in thin filament structure and function, including ACTA1, NEB, TPM3, TPM2, TNNT1, CFL2, KBTBD13, KLHL40, KLHL41, and LMOD3, among others. Diagnosis is confirmed through muscle biopsy showing nemaline rods and genetic testing. There is currently no cure or disease-specific treatment. Management is supportive and includes mechanical ventilation, nutritional support via gastrostomy, physical therapy to manage contractures, and orthopedic interventions as needed. Decisions regarding the extent of life-sustaining interventions are often discussed with families given the severity of the condition.

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