Cobblestone Lissencephaly

What is Cobblestone Lissencephaly?

Cobblestone lissencephaly (COB) previously designated as lissencephaly “type 2″, is a brain malformation consisting of a complex cortical dysplasia with glioneuronal heterotopia on the brain surface, moderate to severe lissencephaly, dysmyelination, hypoplastic brainstem, and dysplastic cerebellum with cysts. Cobblestone lissencephaly occurs in several genetic disorders, with Walker-Warburg syndrome (WWS) being the most severe form; Fukuyama congenital muscular dystrophy (FCMD), the mildest form; and muscle-eye brain (MEB) disease, the intermediate form.

Characteristics

It is characterized by a nodular brain surface, ocular anomolies, and congenital muscular disorders.

Causes

It results from overmigration of the neuroblasts and glial cells beyond the external glial limitations into the subarachnoid space. The following gene mutations/deletions have been identified with cobblestone lissencephaly:  FKTN, FKRP, LARGE, POMGnT1, POMT1 and POMT2.