title: Fetal onset ventriculomegaly and subependymal cysts in a pyridoxine dependent epilepsy patient.
abstract: Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene encoding α-aminoadipic semialdehyde dehydrogenase. The classic clinical presentation is neonatal seizures responsive only to pyridoxine therapy. White matter abnormalities, corpus callosum agenesis or hypoplasia, megacisterna magna, cortical dysplasia, neuronal heterotopias, intracerebral hemorrhage, and hydrocephalus in neuroimaging have been reported in patients with PDE. We report a new patient with asymmetric progressive ventriculomegaly noted on fetal sonography at 22 weeks' gestation. Postnatal brain sonography on day 1 and MRI on day 5 confirmed bilateral asymmetric ventriculomegaly caused by bilateral subependymal cysts. Intractable seizures at age 7 days initially responded to phenobarbital. Markedly elevated urinary α-aminoadipic acid semialdehyde levels and compound heterozygous mutations in the ALDH7A1 gene (c.446C>A/c.919C>T) confirmed the diagnosis of PDE caused by ALDH7A1 genetic defect. Despite the presence of structural brain malformations and subependymal cysts, PDE should always be included in the differential diagnosis of neonatal seizures that are refractory to treatment with antiepileptic drugs.
authors.affiliation: Department of Medical Genetics, University of Alberta, Stollery Children's Hospital, Edmonton, Canada; and.
authors.forename: Shailly
authors.initials: S
authors.lastname: Jain-Ghai
authors.forename: Navin
authors.initials: N
authors.lastname: Mishra
authors.forename: Cecil
authors.initials: C
authors.lastname: Hahn
authors.forename: Susan
authors.initials: S
authors.lastname: Blaser
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
mesh_terms: D001927:Brain Diseases / Q000209:etiology; D003560:Cysts / Q000209:etiology*; D004805:Ependyma; D004827:Epilepsy / Q000150:complications* / Q000175:diagnosis; D005315:Fetal Diseases / Q000175:diagnosis; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology*; D007231:Infant, Newborn; D008297:Male
keywords: ALDHA71 deficiency; pyridoxine dependent epilepsy; subependymal cysts; ventriculomegaly