LAMA2 related congenital muscular dystrophy

LAMA2-related congenital muscular dystrophy (LAMA2-CMD) is a genetic disorder characterized by muscle weakness and wasting, typically presenting at birth or in early infancy. It is caused by mutations in the LAMA2 gene, which encodes the laminin alpha-2 chain, a crucial component of the extracellular matrix in muscle tissue.

Pathophysiology

Diagrammatic illustration of laminin-211 or Laminin-alpha2 chain. The alpha2 chain is shown in red.

The LAMA2 gene provides instructions for making the laminin alpha-2 chain, which is part of the laminin-211 complex. This complex is essential for the structural integrity and function of muscle fibers. Mutations in LAMA2 disrupt the formation of laminin-211, leading to muscle fiber instability and degeneration.

Clinical Features

LAMA2-CMD is characterized by hypotonia (decreased muscle tone), muscle weakness, and delayed motor milestones. Affected individuals may also exhibit joint contractures, scoliosis, and respiratory difficulties.

Types of scoliosis according to Movshovich.

Neurological Involvement

Some patients with LAMA2-CMD may present with white matter abnormalities in the brain, detectable via magnetic resonance imaging (MRI). These abnormalities do not typically correlate with significant cognitive impairment.

Brain MRI of a patient with late-onset LAMA2-MD showing white matter abnormalities (hyperintensities) in T2.

Diagnosis

Diagnosis of LAMA2-CMD is based on clinical evaluation, muscle biopsy, and genetic testing. Muscle biopsy may reveal a deficiency of laminin alpha-2 in the muscle tissue. Genetic testing can confirm mutations in the LAMA2 gene.

Management

There is currently no cure for LAMA2-CMD. Management focuses on supportive care, including physical therapy, orthopedic interventions, and respiratory support. Regular monitoring and multidisciplinary care are essential to address the various complications associated with the disorder.

Research and Animal Models

Research into LAMA2-CMD includes studies on animal models, such as mice, to better understand the disease mechanism and explore potential therapies.

Laminin-alpha2 congenital muscular dystrophy Mouse model.

Prognosis

The prognosis for individuals with LAMA2-CMD varies depending on the severity of the condition. While some individuals may achieve independent ambulation, others may require lifelong assistance and adaptive devices.

Lama2 congenital muscular dystrophy deformities.

Related Pages

• Congenital muscular dystrophy
• Laminin
• Genetic disorders