The congenital muscular dystrophies (CMDs) are a diverse group of muscle disorders with onset at or shortly after birth. There are at least 30 different diseases within the CMDs, each due to a different gene mutation.
Most CMDs affect the extracellular matrix
Muscle cells are embedded in a web-like structure known as the extracellular matrix (ECM). The ECM is a complex mix of molecules, including many kinds of proteins linked to carbohydrates (called glycoproteins). Glycoproteins have multiple roles in the ECM, including transmitting the force of muscle contraction to the skeleton, connecting individual muscle cells to each other, transmitting signals among cells, and promoting development and repair. Many CMDs are due to mutations in glycoproteins themselves, or in the enzymes that create them. One group of CMDs are due to mutations in genes that help glycosylate (add sugar molecules to) the protein alpha-dystroglycan, a key glycoprotein of the ECM.
Loss of glycoproteins due to mutation interferes with normal muscle function. A consequence of most CMD-causing mutations is increased susceptibility to cellular injury from normal contraction, and/or a reduction in the ability to repair damage.
Despite the variety of causative genes, the consequences of CMD are similar among many of the diseases, and so the therapeutic strategies are also similar. These include replacing the defective gene, correcting the defective gene, replacing the defective protein, replacing injured muscle cells, increasing muscle growth, and mitigating the effects of the mutant gene.