Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder, with an estimated incidence of around 1-2/100,000 live births. In about one third of the cases, Walker-Warburg syndrome is due to defects in genes encoding protein O-mannosyltransferases (POMT 1 or 2), or mutations in fukutin or fukutin related protein (FKRP), which all have a role in regulating the interaction between the cytoskeleton and the extracellular matrix in neurons and muscle cells. The syndrome is characterized by the triad of muscular dystrophy, brain anomalies and eye anomalies. In fact, WWS is considered the most severe form of congenital muscular dystrophy (CMD). Brain abnormalities typically include cobblestone lissencephaly and cerebellar malformations, but hydrocephalus, Dandy-Walker malformation and encephaloceles are also regularly described. Eye abnormalities are commonly retinal and anterior chamber malformations, and glaucoma, cataract, microphthalmia and colobomas are occasionally reported. Facial and oropharyngeal malformations, including micrognathia, small mouth opening, cleft lip and cleft palate, have regularly been reported and may lead to difficulties in airway management. Other features such as urogenital malformations (e.g., hydronephrosis, cystic kidneys, genital anomalies), ventricular septal defect, cardiomyopathy, microtia, absent auditory canals, imperforate anus or hypothyroidism have incidentally been described. Patients may be at increased risk for central and obstructive apnoea, seizures and delayed gastric emptying.
A specific therapy is not available. Surgical interventions are commonly required for treatment of hydrocephalus or to restore malformations. Affected patients typically die before the age of 3 of respiratory failure and pneumonia.
Muscle Eye Brain disease shares many characteristics with Walker-Warburg syndrome and has sometimes been used as synonym. However, most authors consider the two entities as different syndromes. Lissencephaly type II is also sometimes used as synonym, but is actually a broader term applying also to other similar syndromes with cobblestone lissencephaly.