Familial hydrocephalus with normal cognition and distinctive radiological features

Hydrocephalus is a clinically and genetically heterogeneous condition. Individuals with posterior fossa abnormalities have an increased risk of developing hydrocephalus. The Dandy-Walker malformation, Dandy-Walker variant, and mega-cisterna magna (MCM) seem to represent a continuum of developmental anomalies of the posterior fossa. Here we describe the natural clinical history and the radiological features of a family with autosomal or X-linked dominant inheritance of MCM and hydrocephalus of variable severity. The affected family members demonstrate similar structural brain abnormalities including midline cyst, colpocephaly, MCM with a large posterior fossa and minimal vermian hypoplasia. The cognitive development of the affected individuals is normal. L1CAM and FOXC1 gene involvement in the pathogenesis of the disease in this family was excluded. The rare possibility of autosomal dominant or X-linked dominant inheritance and variable penetrance and expressivity must always be considered in genetic counseling of families with hereditary hydrocephalus.