LAMA2 Congenital Muscular Dystrophy (LAMA2-CMD)
LAMA2-CMD is the result of genetic mutations of the laminin protein
called merosin found in the muscle cells. Affected individuals with
LAMA2-CMD are characterized by muscle weakness and contractures
and may be born with complete or partial merosin deficiency
depending on the genetic mutations.
Characteristics of LAMA2 Congenital Muscular Dystrophy
Respiratory and feeding complications
White matter changes
Prof. Umbertina Conti Reed, Arq. Neuro-Psiquiatr. vol.67 no.1 São Paulo Mar. 2009
The Physiology of LAMA2 Congenital Muscular Dystrophy
LAMA2-CMD is caused by two mutations in the LAMA2 (laminin alpha 2) gene which produces merosin, one of the laminin proteins. Merosin makes up part of the extracellular matrix of the muscle cell membrane. The extracellular matrix forms the outside environment around the muscle cell. It performs critical functions by supporting muscle cell stability and regeneration while allowing the muscle cell to adhere to the matrix. Laminins plays a major role in binding itself and other proteins together not only in the extracellular matrix but also to the muscle cell membrane. Laminins help to maintain muscle fiber stability.
Affected individuals with LAMA2-CMD are born with complete or partial merosin deficiency depending on where the genetic mutations are located.
Those with complete merosin deficiency will have early onset of the disorder (present at birth) with hypotonia (decreased muscle tone or floppiness), progressive joint contractures, and will develop breathing and feeding problems early in life. Scoliosis and rigid spine can develop. Some will have cardiac abnormalities.
Those with partial merosin deficiency may have later or milder onset (late childhood/early adulthood). Symptoms may be milder with some affected individuals able to walk into adulthood.
White matter abnormalities in MRI images of the brain can be present across the LAMA2-CMD spectrum and some affected individuals will develop seizures.
Inheritance and Genetic Testing
LAMA2-CMD is inherited in an autosomal recessive fashion, meaning there must be two pathogenic mutations present to cause symptoms. These mutations may be inherited from each parent, or may be denovo (spontaneous). Because the LAMA2 gene is quite large and researchers are still working to fully map it, it is not uncommon for affected individuals to only have had one of the two mutations identified through genetic testing. One identified mutation along with identifiable physical characteristics, elevated CK, white matter changes, and partial or absence of merosin on muscle or skin biopsy can lead to a confirmed diagnosis of LAMA2-CMD.