periventricular nodular heterotopia type 1

periventricular nodular heterotopia type 1

An X-linked dominant developmental disorder (OMIM:300049) characterised by the presence of periventricular nodules of cerebral grey matter, due to a failure of neurons to migrate normally from the lateral ventricular proliferative zone (where they are formed) to the cerebral cortex. Heterozygous females have normal intelligence but suffer from seizures and various manifestations outside the CNS, especially of the cardiovascular system (e.g., patent ductus arteriosus; bicuspid aortic valve; vasculopathy and/or coagulopathy leading to stroke; ruptured aneurysm). Affected males typically die in the prenatal or perinatal period.

Molecular pathology
Defects in FLNA cause periventricular nodular heterotopia type 1. A less common, autosomal recessive form of periventricular nodular heterotopia is caused by mutations in ARFGEF2, which encodes ADP-ribosylation factor guanine nucleotide-exchange factor, a protein involved in membrane trafficking.