NeurometPlus

Incidence

The syndrome is familial and is transmitted as an autosomal recessive trait. Precise epidemiological data are not available. This form of congenital muscular dystrophy has, however, been described in most ethnic groups.

Clinical Characteristics

Characteristic features are congenital muscular dystrophy in combination with type II lissencephaly and retinal malformation. The central nervous system features typically predominate the clinical presentation. Affected children have virtually absent psychomotor development; encephaloceles and severe hydrocephalus are often detected prenatally. On brain imaging, complete type II lissencephaly or agyria combined with pontocerebellar hypoplasia are visible. An additional feature is blindness, secondary to both anterior and posterior chamber eye malformations. Muscle bulk is reduced, and contractures may already be present at birth or develop rapidly thereafter. The most relevant differential diagnosis is with other conditions with lissencephaly. Presentation is in utero or at birth with hypotonia, poor suck and swallow, and contractures. Progressive disease results in no developmental progress. The average time of death is 9 months. Eye abnormalities include microphthalmos, hypoplastic optic nerve, ocular colobomas, retinal detachment, cataracts, glaucoma, iris malformation, and corneal opacities, all of which lead to blindness. Brain abnormalities include complete type II lissencephaly with agyria. Other cerebral defects include a thin cortical mantle, an absent corpus callosum, fusion of the cerebral hemispheres, and hypoplasia of the pyramidal tracts. Posterior fossa abnormalities include severe cerebellar atrophy of the vermis and hemispheres, arachnoid cysts, and a hypoplastic brainstem. Meningocele or encephalocele, usually of the posterior fossa, are present in 25% of patients. Microcephaly, ventricular dilation, and obstructive hydrocephalus are common. The most severe MRI changes are seen in WWS, with most patients having severe agyria, pontocerebellar hypoplasia, and (in many patients) encephalocele or myelomeningocele. It is due to defects of glycosyltransferases (dystroglycanopathies). Walker-Warburg syndrome is the most severe of the alpha-dystroglycanopathies.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

It is usually a clinical diagnosis. Brain MRI and ophthalmological examination will help to recognize the typical associated features. Serum CK levels are typically elevated (more than 10 times normal values). A muscle biopsy is necessary. The immunostaining of skeletal muscle with alpha-dystroglycan will typically show virtually absent staining using antibodies that recognize a glycosylated epitope. Mutation analysis of the mannosyltransferase 1 and 2 genes are necessary to confirm the involvement of these genes. Recessive mutations in the O-mannosyltransferase 1 gene have been reported in approximately 20% of cases. Recently, mutations in the O-mannosyltransferase 2 gene were found in another 20% of cases.