Walker-Warburg Syndrome

Background and History: 

This disorder is named after the American neurosurgeon A.E. Walker, and the Danish ophthalmologist Mette Warburg.  It belongs to a group of diseases with brain, eye, and muscle abnormalities caused by mutations that impact an important metabolic pathway called glycosylation.

Clinical Correlations: 

The title refers to a category of disease rather than a single entity.  It is sometimes called muscle-eye-brain(MEB) disease.  The responsible gene mutations are all involved in a common metabolic pathway.  Severe malformations of the brain and eye plus a congenital form of muscular dystrophy seem to be the common manifestations but there is considerable clinical variation in the signs and symptoms.  Infants are affected a birth and many never survive beyond one year of age.  In these individuals, normal developmental milestones are often delayed and sometimes never achieved.  Some have seizures but these are uncommon.  Hydrocephalus is sometimes seen.  Others are more mildly affected and able to walk and speak but this is uncommon.

The eyes may be small and glaucoma may be present.  Often the retina is malformed and the optic nerve is not fully developed or is pale.  Vision is likely severely depressed but measurements are difficult to make due to the severity of the mental retardation. 

Genetics: 

This is an autosomal recessive disorder requiring the presence of two mutations before it can be expressed.  At least 6 genes may contain mutations that cause these similar conditions.  Two carrier parents with one mutation are clinically normal but have a risk of 25% that each of their children may inherited this condition. 

Diagnosis and Prognosis: 

Usually signs of the disease are present at birth with ophthalmologists and neurologists collaborating in the diagnosis.  The prognosis is poor and many infants die in the first year of life.  There is no effective treatment.  Brain MRIs may be useful for the diagnosis. 

Additional Information
Inheritance/Pedigree: 
Autosomal recessive