Walker-Warburg syndrome (WWS) is the most severe type of congenital muscular dystrophy, affecting the muscles, brain, and eyes. The disease is also sometimes called dystroglycanopathy because it is caused by mutations in genes such as POMT1, POMT2, CRPPA, FKTN, FKRP, and LARGE1 that play an essential role in the synthesis of a protein called alpha-dystroglycan. This protein is necessary for the structural and functional integrity of muscles and nerve cells.
The signs and symptoms of WWS are already present at birth and in early infancy. Occasionally, they can be detected prenatally with the help of imaging techniques.
Muscle problems in WWS include weak skeletal muscle tone (hypotonia) and strength, which worsen over time and cause mobility issues. Babies affected by WWS are sometimes described as “floppy.” Joint deformities are also sometimes observed. These may become fixed, turning into contractures, and can restrict movement.
There are several structural and functional defects in the eye that can cause partial or complete blindness in patients with WWS. Some of these include:
- Microphthalmia, or small eyeballs;
- Buphthalmos, or enlarged eyeballs caused by increased pressure in the eyes;
- Cataracts, or the clouding of the lens;
- Retinal detachment, where the thin layer of the retina pulls away from the layer of blood vessels that provide oxygen and nutrients;
- Glaucoma, or damage to the optic nerve that relays visual information from the eyes to the brain;
- Structural defects in the iris, which controls the diameter and size of the pupil and affects the amount of light that reaches the retina;
- Corneal opacities, or the scarring or clouding of the cornea, the transparent, dome-shaped structure in front of the retina;
- Optic nerve hypoplasia, or underdeveloped optic nerve;
- Ocular colobomas, or holes in eye structures, including the iris, retina, and others because the normal tissue is not formed during eye development;
- Microcornea, or a smaller-than-normal cornea.
Defects in the brains of WWS patients can cause significant intellectual disabilities. Some patients may also experience seizures.
The characteristic brain abnormalities include:
- Cobblestone lissencephaly, also known as type 2 lissencephaly, caused by nerve cells migrating to the wrong places. The surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones);
- Hydrocephalus, where the cerebrospinal fluid builds up in the ventricles of the brain and increases the pressure within the head;
- Severe atrophy (degeneration) or hypoplasia (underdevelopment) of the cerebellum, which is located at the base of the brain and controls muscle function and movement;
- The fusion of the left and right hemispheres of the brain;
- A flattened brain stem, the portion of the brain that connects it to the spinal cord;
- Encephalocele, where part of the brain protrudes out through the skull bone;
- Absence of corpus callosum, the band of white matter that connects the left and the right brain hemispheres.
Other anomalies observed in some WWS patients include a small penis, undescended testes, and, rarely, facial malformations such as low-set or prominent ears and cleft lip or palate.
Last updated: Aug. 21, 2019
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