Causes of WWS

Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy. It is an inherited condition that primarily affects the skeletal muscles, brain, and the muscles in the eyes. The symptoms of this condition manifest in early infancy.

Mutations in several genes have been linked to WWS. Although the function of all the identified genes is not clear, most carry instructions to make proteins that are involved in modifying another protein, called alpha-dystroglycan.


Alpha-dystroglycan is a protein that provides stability to the skeletal muscles and protects them from degradation. It helps anchor the muscle cells to the surrounding matrix and forms a network that promotes cell-to-cell communication. Alpha-dystroglycan also assists the movement of nerve cells in the brain during the early stages of development.

For alpha-dystroglycan to perform its functions correctly, it must first undergo a chemical modification called glycosylation, which is the addition of a sugar molecule.

How mutations affect the function of alpha-dystroglycan

Mutations in genes that encode for proteins that glycosylate alpha-dystroglycan cause these proteins to be non-functional. As a result, alpha-dystroglycan fails to undergo the correct glycosylation and  function correctly.

Any defect in the workings of alpha-dystroglycan destabilizes the skeletal muscles and causes repeated damage to the muscle fibers, resulting in their progressive degeneration.

Defects in alpha-dystroglycan also hinder the proper migration of nerve cells in the brain during early developmental stages and cause them to lose track of their migration path. Instead of stopping at their destination, they continue to leave the brain and enter the fluid surrounding it.

Genes associated with WWS

Some commonly reported WWS-associated genes and the proteins they encode for include:

POMT1 and POMT2 — O-mannosyltransferase enzyme complex;

CRPPA — CDP-L-ribitol pyrophosphorylase A;

FKTN — fukutin;

FKRP — fukutin-related protein.


Last updated: Aug. 21, 2019


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