LAMA2-related muscular dystrophy is a disorder that causes muscle weakness and wasting. The condition is a result of mutations in the LAMA2 gene that contains instructions for the body to make the laminin alpha2 protein. This protein is part of the laminin 2 (also called merosin) and laminin 4 complexes, which are important skeletal muscle components. There are at least two types of this condition:
Early-onset LAMA2-related MD is the most common presentation of this condition. It is apparent at birth or within the first few months of life, and thus, considered part of a class of muscle disorders called congenital muscular dystrophies. Low muscle tone and muscle weakness are severe and most affected infants experience delays or fail to reach many motor milestones. Most affected infants can sit unsupported and some can stand without assistance. Very few children with the severe form are ever able to walk without help. In addition, affected newborns may experience breathing difficulties that progressively worsen with age. Feeding difficulties can result in poor weight gain and growth. Other symptoms can include stiff joints, dislocation of the hip, progressive curvature of the spine, weak eye muscles, and seizures. Intellectual disability is only seen in a small percentage of patients, who mostly have structural malformations of the brain and/or seizures.
Late-onset LAMA2-related MD occurs later in childhood or in adulthood. Signs and symptoms of this form tend to be milder than the early-onset type and are similar to those of a group of muscle disorders classified as limb-girdle muscular dystrophies. In the late-onset form, the muscles most affected are those closest to the body, such as the shoulders, upper arms, pelvic area, and thighs. Children with late-onset LAMA2-related MD sometimes have delayed development of motor skills such as walking, but typically achieve the ability to walk without assistance. Over time, they may develop rigidity of the back, joint stiffness, progressive curvature of the spine, breathing problems, and heart issues (arrhythmia or weakening of the heart muscles, known as cardiomyopathy).
The worldwide occurrence of LAMA2-related MD is unknown. Where estimated, the occurrence of congenital muscular dystrophies are estimated to be between 1 in 26,000 and 1 in 132,000. However, the number of cases attributed to mutations in LAMA2 varies by country and has been reported between ~6% and ~66%. Of note, one large study from northern England estimated the occurrence of LAMA2-related MD to be approximately 1 in 166,000 births, and a high frequency of the disease has been described in the Irish and Kenyan populations.
Treatment is symptomatic, with the objective of optimizing each patient's abilities, and is usually managed by a team of doctors. For infants and children with early-onset LAMA2-related MD, it may include supplemental feeding, breathing support, physical therapy, orthotics for joint stiffness, occupational therapy, and speech therapy. Seizures or other neurological complications generally require specific medications. Those with the late-onset form benefit from regular physical therapy to stretch the joints and spine, and may need care for progressive breathing difficulties. Monitoring for issues over time, like breathing and heart complications, is also typically recommended for any individual with this condition.
Because of the serious health problems that occur in the early-onset form of the disorder, especially breathing issues, many affected individuals do not survive past adolescence. Those with the rarer, late-onset form have progressive muscle weakness, but life expectancy is typically unaffected.
The CMD International Registry is a patient self-report registry, with the goal to register the global congenital muscle disease population, including congenital myopathy and congenital muscular dystrophy.
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