Loss-of-function mutations in the X-linked gene FLNA can lead to abnormal neuronal migration, vascular and cardiac defects, and congenital intestinal pseudo-obstruction (CIPO), the latter characterized by anomalous intestinal smooth muscle layering.
FLNAp.V528M was initially detected in a female autopsy case of X-linked bilateral periventricular nodular heterotopia (BPNH), a neuronal migration disorder characterized by subependymal nodules of gray matter.
Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs.3-6).