Summary
Cobblestone lissencephalies or cobblestone dysplasia (also known as type 2 lissencephaly) is a type of lissencephaly characterized by a bumpy or granular aspect of the brain surface, associated with shallow sulci (hence the aspect of a lissencephaly), abnormal myelination of the white matter, which may have a cystic appearance in proximity to the cortex, enlarged ventricles, brainstem hypoplasia, cerebellar especially vermis hypoplasia. Reliable population data to estimate the incidence at birth are not available (approximateprevalence 1 in 100,000 births). The most common form is characterized by the association of hydrocephaly (H), agyria (A) (complete absence of circumvolutions), and retinal dysplasia (RD), with or without encephalocele (E). All these features explain the acronym HARD(E), a syndrome also known as Walker-Warburg syndrome, which is usually lethal within the first months of life. In 20% of cases, HARD(E) syndrome has been associated with a mutation of the POMT1 gene, which maps to 9q34. Mutations in the fukutin gene are exceptionally retrieved. Cobblestone lissencephalies also include the Fukuyama syndrome (congenital muscular dystrophy due to a mutation in fukutin on 9q31 and the Muscle-Eye-Brain (MEB) disease, caused by mutations in POMGNT1 gene, which has been mapped to 1p34-p33. *Author: Prof. A. Verloes (March 2004)*.
