Distal spinal muscular atrophy autosomal recessive 4 (DSMA4) is a form of distal spinal muscular atrophy, which is a group of rare genetic disorders that cause a loss of cells in the spinal cord that control muscles (motor neurons). This loss of motor neuron cells leads to a decrease in muscle tissue (atrophy) in the legs. Individuals with DSMA4 first show symptoms in childhood. The first symptom of the disease is weakness and atrophy in the lower (distal) part of the legs. As time goes on, the weakness and atrophy may spread to upper (proximal) muscles of the legs, the outer (distal) muscles of the arms, or to the muscles used for breathing.
DSMA4 is caused by changes (mutations) in the PLEKHG5 gene. This gene normally provides instructions for the body to create a protein that helps send signals from the brain to the muscles through motor neurons. However, when the PLEKHG5 gene is mutated, clumps of the protein form in the motor neurons, leading to the muscle weakness and atrophy seen in this disease. People have two copies of the PLEKHG5 gene. DSMA4 is inherited in an autosomal recessive manner, which means both copies of the gene must have a mutation in order for a person to have the disease. If a person has a mutation in only one of the two copies, they are known as a carrier and will not show signs of the condition.
DSMA4 is usually considered as a diagnosis in a child with muscular atrophy and weakness. Genetic testing is used to confirm the diagnosis. There is currently not a cure for DSMA4. Treatment options depend on the symptoms, but usually include supportive therapies. In some severe cases, breathing support may be necessary. If your child has been diagnosed with DSMA4, talk with their doctor about the current treatment options. Support groups can provide additional information and connect you with other families affected by DSMA4.