Familial periventricular heterotopia : Mutation in the FLN1 gene

Abstract

Familial bilateral periventricular heterotopia (BPNP) is a neuronal migration disorder characterized by the presence of uncalcified nodules of neurons ectopically situated along the surface of the lateral ventricles. It is an X-linked dominant condition and has been associated with protein truncations or splicing mutations, which tend to cluster at the N-terminal of the FLN1 protein causing severe predicted loss of the protein function. Prenatal lethality is associated with hemizygous boys. We would like to present two sisters who presented with epilepsy. Their MRI investigation showed bilateral periventricular nodular heterotopia. A third sister presented with recurrent miscarriages but on investigation, her MRI also showed signs of periventricular heterotopia. Their mental capabilities were normal. DNA analysis of their DNA for mutations in the FLN1 gene showed a dinucleotide substitution leading to protein truncation, which was maternally inherited.