Cobblestone Lissencephaly with Normal Eyes and Muscle

Abstract

Cobblestone lissencephaly is the characteristic brain malformation observed in Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome (WWS). The diagnostic criteria for all three require the presence of congenital muscular dystrophy, and criteria for MEB and WWS require retinal abnormalities. We report three patients from two consanguineous families of Middle Eastern origin with cobblestone lissencephaly but no abnormalities of the eyes or muscle. Based on the current diagnostic criteria for the cobblestone lissencephaly syndromes, this disorder must be classified separately from the others, but it may well be allelic to MEB and WWS. Linkage studies have excluded the gene for this disorder from the region of the FCMD gene on chromosome 9q31-32.

GPR56 and the Developing Cerebral Cortex: Cells, Matrix, and Neuronal Migration

“…Some of the MRI findings, namely abnormal signal in the cerebral white matter and hypoplasia of the pons and cerebellar vermis, have many similarities to those seen in conditions with cobblestone lissencephaly, such as muscle-eye-brain disease (MEB), Fukuyama congenital muscular dystrophy (FCMD), and Walker-Warburg syndrome (WWS). Indeed, some of the molecularly confirmed BFPP cases were originally diagnosed as cobblestone lissencephaly with normal eyes and muscle [9,21]. Therefore, it has been suggested that BFPP should be renamed as cobblestone-like cortical malformation (Dobyns, personal communication).…”

Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debré type

“…[32][33][34] Based on a brain imaging appearance that closely resembles MEB, one of the authors first reported this syndrome as "cobblestone lissencephaly with normal eyes and muscle" in 1996. 35 Other authors described the same malformation alternatively as pachygyria 36 or polymicrogyria. 33,34,37 Interestingly, the GPR56 protein is heavily glycosylated.…”

Genetics of the polymicrogyria syndromes

“…21 Thus it is not surprising that BFPP had previously been termed cobblestone lissencephaly with normal eyes and muscle. 35 The main clinical features of BFPP include global developmental delay, dysconjugate gaze (esotropia), pyramidal and cerebellar signs, and seizures, which occur in 94% of patients and are mostly generalised. [26][27][28] Although dysconjugate gaze is common in patients with severe static encephalopathy, it may help to distinguish BFPP from other bilateral polymicrogyria syndromes, in which it has not been described.…”