LAMA2

LAMA2 is a human gene that encodes laminin subunit alpha-2, a component of the extracellular matrix. The alpha-2 chain combines with beta-1 and gamma-1 chains to form laminin-211, also known as merosin, a major constituent of basement membranes in skeletal muscle and peripheral nerves. Laminin-211 interacts with receptors such as dystroglycan to link the extracellular matrix to the cytoskeleton, contributing to sarcolemma stability and muscle fiber integrity.

Pathogenic variants in LAMA2 cause LAMA2-related muscular dystrophy, most commonly presenting as merosin-deficient congenital muscular dystrophy type 1A (MDC1A). The disorder is inherited in an autosomal recessive manner. Affected individuals typically exhibit severe hypotonia at birth or early infancy, feeding and respiratory difficulties, progressive generalized weakness, and contractures. White matter changes on brain MRI due to hypomyelination are observed in many patients, though intelligence is usually normal or only mildly affected.

Diagnosis is established by molecular genetic testing of LAMA2 and, in some cases, muscle biopsy showing absent or reduced merosin immunostaining. Management is supportive and multidisciplinary, focusing on respiratory support, physical and occupational therapy, mobility aids, nutritional support, and monitoring for orthopedic complications. Genetic counseling is recommended for families due to the autosomal recessive inheritance pattern.

Research efforts include developing gene therapy and other strategies to restore laminin-211 function or stabilize the dystroglycan complex, but as of the current knowledge, there are no approved disease-modifying therapies for LAMA2-related muscular dystrophy.