Walker-Warburg Syndrome Health Article

Definition

Walker-Warburg syndrome is a congenital disorder of the central nervous system involving fatal neurological lesions. Multiple malformations of the brain, eyes, and muscle tissue distinguish WWS from similar malformation syndromes. It is also known by the acronym HARD +/- E syndrome (hydroencephalus, agyri, retinal dysplasia, plus or minus "e" for encephalocele).

Description

Affected individuals typically show a combination of severe brain, eye, and muscle defects. Multiple malformations of the brain include type II lissencephaly,a condition in which the brain lacks normal convolutions and is unusually smooth without folds. Eighty-four percent of the infants with WWS have macrocephaly (an enlarged head). In half of these cases, the macrocephaly is apparent at birth, and in a quarter of the cases it develops postnatally. Hydrocephalus, or excessive accumulation of cerebrospinal fluid around the brain, occurs in 95% of infants with WWS. This fluid fills abnormally large ventricles or spaces in the brain. Fifty percent of affected infants have an encephalocele, or gap in the skull that does not seal. The meninges or membranes that cover the brain may protrude through this gap. The formation of an encephalocele may be associated with the failure of the neural tube to close during development of the fetus. A malformed cerebellum characterizes the syndrome as well as distinct muscle abnormalities, including congenital muscular dystrophy.

Ocular defects occur in 100% of infants with WWS. The most common are abnormally small eyes and retinal abnormalities, which arise from the improper development of the light sensitive area at the back of the eye. Cataracts may also be present and more than three quarters of the infants born with WWS have a defect in the anterior chamber of the eye. WWS syndrome leads to severely retarded mental development and is often lethal in infancy.

Genetic profile

WWS is inherited in an autosomal recessive pattern. Offspring of parents who have had one affected infant have a 25% chance of having WWS. The locations of the causitive genes remains unknown.

Demographics

WWS is extremely rare. Cases described in the literature cite siblings with WWS born to consanguineous (closely related) parents as well as cases in families not known to be at risk.