SNP Shot: Genomic Insights

LAMA2-related muscular dystrophy is a condition characterized by muscle weakness and wasting (atrophy) in skeletal muscles, which are responsible for movement. The severity of this condition can range from a severe form that appears early in life to a milder form that develops later.

The early-onset form of LAMA2-related muscular dystrophy is typically noticeable at birth or within the first few months of life. It is classified as a congenital muscular dystrophy, sometimes referred to as congenital muscular dystrophy type 1A. Infants with this condition may exhibit significant muscle weakness, reduced muscle tone (hypotonia), minimal spontaneous movement, and joint deformities (contractures). Weakness in the facial and throat muscles can lead to difficulty feeding and failure to thrive. Respiratory insufficiency, caused by weakened chest muscles, can result in a weak cry and breathing difficulties, increasing the risk of frequent and potentially life-threatening lung infections.

As children with early-onset LAMA2-related muscular dystrophy grow, they commonly develop scoliosis, an abnormal sideways curvature of the spine that worsens over time, and lordosis, an exaggerated inward curve of the lower back. Many children with this form of the condition do not learn to walk. Speech difficulties may arise due to weakness in the facial muscles and an enlarged tongue. Seizures occur in approximately one-third of individuals with early-onset LAMA2-related muscular dystrophy. In rare cases, heart problems may also develop.

The late-onset form of LAMA2-related muscular dystrophy manifests later in childhood or adulthood, with symptoms resembling those of limb-girdle muscular dystrophies. In this form, the muscles closest to the body (proximal muscles) are most affected, including those of the shoulders, upper arms, pelvic region, and thighs. Children with late-onset LAMA2-related muscular dystrophy may experience delays in motor skill development, such as walking, but generally achieve independent ambulation. Over time, they may develop back stiffness, joint contractures, scoliosis, and breathing problems. However, most individuals with the late-onset form retain the ability to walk and climb stairs.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that both copies of the LAMA2 gene in each cell must have mutations for the condition to develop. Individuals with autosomal recessive conditions inherit one mutated copy of the gene from each parent, who are typically carriers and do not exhibit symptoms of the condition themselves.