Autosomal recessive frontotemporal pachygyria

Abstract

Pachygyria is a cortical malformation that results from the abnormal migration of neurons. Regions of the brain with pachygyria have an abnormally thick cortex that lacks normal folding and has deficient layering. We describe three siblings, born to nonconsanguineous Mexican parents, who have bilateral frontotemporal pachygyria without polymicrogyria. The pachygyria is accompanied by moderate mental retardation, esotropia, and either hypertelorism or telecanthus. They are otherwise morphologically normal and do not have microcephaly. Two experienced a single seizure in infancy. The characteristic phenotype present in this family suggests a new genetic syndrome that is likely inherited as an autosomal recessive trait.

Genetics of the polymicrogyria syndromes

“…Interestingly, esotropia was recently described in a family with autosomal recessive frontotemporal pachygyria without polymicrogyria. 36 These patients lack the cerebellar and pyramidal features described in BFPP and their seizure phenotype is less severe. However, linkage to the BFPP locus has not been ruled out in this family.…”

Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant

“…Similar phenotypes have been reported a few times, but with no underlying cause identified (MIM: 610279 ). 11 , 12 , 13 , 14 We performed trio-based whole-exome sequencing in two families with TLIS and detected a homozygous mutation of CRADD (GenBank: NM_003805.3 ; c.382G>C [p.Gly128Arg] [MIM: 603454 ]) in two siblings from a Mennonite family. Targeted re-sequencing of an additional 18 unrelated individuals with TLIS identified two other homozygous missense mutations in CRADD (c.508C>T [p.Arg170Cys] and c.509G>A [p.Arg170His]) in families of Turkish and Finnish ancestry, respectively, and a fourth missense change (c.491T>G [p.Phe164Cys]) in trans with a 3.07 Mb deletion of chromosome 12q22 that includes CRADD in an affected child of a fourth family.…”

The syndrome of pachygyria, mental retardation, and arachnoid cysts maps to 11p15

“…Several genes are known to cause familial forms of lissencephaly/pachygyria including LIS1 at 17p [Hattori et al, 1994], DCX on Xq [Pilz et al, 1998], RELN on 7q [Hong et al, 2000], and ARX on Xp [Kitamura et al, 2002]. Recently Ramirez et al 2004 described a syndrome of autosomal recessive frontotemporal pachygyria [Ramirez et al, 2004]. However, normal genitalia, cerebellar structures, and opthalmologic findings distinguish the present family from those previously presented.…”