Walker-Warburg syndrome

Abstract

Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of α-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/ dystrophic muscle pathology and altered α-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.

Walker-Warburg syndrome diagnosed by findings of typical ocular abnormalities on prenatal ultrasound

“…cerebral and ocular anomalies [1]. It has recently been shown that WWS is the result of a defective Oglycosylation of α-dextroglycan, which plays a key role in neuronal migration [2]. This defect is caused by mutation in the POMT1, POMT2, FKRP and Fukutin genes.…”

“…Walker-Warburg syndrome (WWS) is a rare, lethal autosomal recessive disorder characterized by congenital muscular dystrophy, brain and eye anomalies: hydrocephalus, abnormal gyration, retinal dysplasia and encephalocele (mnemonic, HARD + E) [1,2].…”

Congenital basis of posterior fossa anomalies

“…Most patients die by the third year of life. 35,36 Joubert syndrome. Joubert syndrome represents a group of sporadic and autosomal recessive disorders that manifest clinically as ataxia, hypotonia, neonatal abnormal breathing, facial dysmorphism, and intellectual disability.…”

POMT1-Associated Walker-Warburg Syndrome: A Disorder of Dendritic Development of Neocortical Neurons

“…[8] ) as well as the application of in vivo MRI [1] . At present, the diagnosis of WWS is based on the presence of four major fi ndings [27] : (a) the presence of congenital muscular dystrophy with hypoglycosylation of alpha-dystroglycan, (b) increased blood levels of creatine kinase, (c) the presence of ocular abnormalities in the anterior or posterior eye chamber, and (d) the disturbed neuronal migration resulting in cobblestone (type II) lissencephaly with concomitant hydrocephalus and abnormal development of cerebellum and brain stem.…”