Nemaline myopathy

Nemaline myopathy (NM), also known as nemaline rod myopathy, is a group of inherited neuromuscular disorders characterized by the presence of rod-shaped structures called nemaline bodies (or nemaline rods) in skeletal muscle fibers on biopsy. It is one of the most common congenital myopathies. The disease primarily affects skeletal muscles, leading to muscle weakness that is typically most pronounced in the face, neck, and proximal limb muscles. Respiratory muscles are frequently involved, and respiratory insufficiency is a major cause of morbidity and mortality, particularly in the severe neonatal form. Nemaline myopathy is clinically heterogeneous and has been classified into several forms based on severity and age of onset: severe congenital (neonatal), intermediate congenital, typical congenital (the most common form, presenting in infancy or early childhood), childhood-onset, and adult-onset forms. Common features include hypotonia, generalized muscle weakness, feeding difficulties, a thin and elongated face, high-arched palate, and delayed motor milestones. Patients with the typical congenital form often achieve ambulation but may have progressive weakness over time. The severe neonatal form presents with profound hypotonia, minimal spontaneous movement, severe respiratory failure, and arthrogryposis, and is often fatal in infancy. At least 13 genes have been associated with nemaline myopathy, including NEB (the most commonly implicated gene, accounting for approximately 50% of cases), ACTA1, TPM3, TPM2, TNNT1, CFL2, KBTBD13, KLHL40, KLHL41, LMOD3, MYPN, MYO18B, and RYR3. These genes encode proteins involved in the structure and function of the thin filament of the sarcomere. There is currently no cure or disease-specific treatment for nemaline myopathy. Management is supportive and multidisciplinary, including respiratory support (non-invasive ventilation or tracheostomy), nutritional support (gastrostomy feeding if needed), physical therapy, orthopedic interventions for scoliosis and contractures, and regular monitoring of cardiac and respiratory function. Research into potential therapies, including gene therapy and pharmacological approaches targeting muscle function, is ongoing.

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