Childhood-onset nemaline myopathy

Childhood-onset nemaline myopathy (also called childhood-onset NM or typical nemaline myopathy) is a rare inherited neuromuscular disorder characterized by progressive or nonprogressive muscle weakness that becomes apparent during childhood, typically between 1 and 10 years of age. It belongs to the broader group of nemaline myopathies, which are defined by the presence of rod-shaped structures called nemaline bodies (or nemaline rods) visible on muscle biopsy. The disease primarily affects skeletal muscles, leading to generalized muscle weakness that is often more prominent in proximal muscles (those closer to the trunk), facial muscles, and the muscles of the neck and limbs. Affected children may present with delayed motor milestones, difficulty running or climbing stairs, facial weakness with an elongated face, a high-arched palate, nasal speech, and reduced muscle bulk. Respiratory muscles can also be involved, potentially leading to respiratory insufficiency that may require ventilatory support. The childhood-onset form is generally considered to have a more favorable prognosis compared to the severe congenital form of nemaline myopathy, though the clinical course is variable. Some patients remain relatively stable, while others experience slow progression of weakness over time. Skeletal complications such as scoliosis, foot deformities, and joint contractures may develop. Cardiac involvement is uncommon but has been reported in rare cases. Nemaline myopathy can be caused by pathogenic variants in several genes encoding components of the thin filament of the sarcomere, including NEB (nebulin), ACTA1 (skeletal muscle alpha-actin), TPM3, TPM2, TNNT1, CFL2, KBTBD13, KLHL40, KLHL41, and LMOD3, among others. There is currently no cure or disease-specific treatment for childhood-onset nemaline myopathy. Management is supportive and multidisciplinary, including physical therapy to maintain mobility and prevent contractures, respiratory monitoring and support when needed, orthopedic interventions for skeletal deformities, and speech therapy for feeding or swallowing difficulties.

Common questions about Childhood-onset nemaline myopathy