Types of Congenital MD

At least 30 different types of CMD are now recognized (see the Types of CMD chart). At first glance, the various types of CMD seem to have little in common other than their early onset. But on the molecular level, the types can be grouped how their faulty protein affects cells.

A very small group of CMDs are linked to proteins that affect what happens inside muscle fibers, affecting how the fibers process signals from the nervous system, for example, or how they handle calcium.

But the vast majority of CMD types are related to proteins that make up or interact with the extracellular matrix that surrounds muscle fibers (see CMD: The Cellular View). 

Several types of CMD that arise from gene mutations that initially seemed unrelated now appear to be related to defects in proteins that "sugar-coat" (glycosylate) a matrix protein, allowing it to connect with other proteins.

The extracellular matrix and CMD

The extracellular — outside the cell — matrix is the substance that surrounds the cells of a tissue, such as muscle, providing physical and biochemical support.

An important role of the matrix around muscle fibers is force transmission. For a muscle to pull against bones, it needs to have contact with something that transmits force from the muscle fibers onto the tendons and bones.

When all is going well, the matrix transmits that force, as well as chemical signals that muscles need to stay healthy.

The matrix is a key supporting structure for the survival and regeneration of muscle. When cells lose touch with their surrounding matrix  — as happens in most types of CMD  — trouble follows.

CMD: The cellular view

Muscle fibers are surrounded by a membrane that separates the inside of the fiber from the material outside the fiber — the extracellular matrix.
Most of the molecular defects that cause congenital muscular dystrophies affect proteins in the extracellular matrix, such as laminin 211, integrin, collagen 6 or alpha-dystroglycan.
The proteins known as fukutin, fukutin-related protein, POMT1, POMT2, POMGnT1, LARGE and others all participate in a special “sugar coating” (glycosylation) of alpha-dystroglycan. The sugar coating is shown as the blue, branchlike structures in this illustration. The branches are known as glycans.
Various other proteins shown — such as the sarcoglycans and dystrophin — can, when flawed or missing, cause muscular dystrophies other than CMD.
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