Novel cardiac findings in periventricular nodular heterotopia

Periventricular nodular heterotopia (PNH) is a set of neuronal migration disorders that occur during fetal development. Neurons in the brain fail to migrate from the lining of the lateral ventricles to the cortex of the brain. When the neurons fail to migrate, ectopic neuronal nodules form. Epilepsy is a common symptom of PNH. The majority of PNH cases appear to be due to mutations in filamin A, an X-linked gene. Most of the affected individuals are female because affected males typically die in utero. Filamin A anchors integral membrane proteins to the cytoskeleton by binding actin filaments in the cytoplasm. Both animal and human studies indicate that filamin A also plays a role in blood vessel development. In this report, we describe novel cardiac findings in an 18-month-old girl with PNH associated with a nonsense mutation in FLNA, including a dysplastic pulmonary valve and clefting of the mitral valve. These findings broaden the range of cardiac anomalies associated with filamin A mutations to include abnormality of the pulmonary valve and clefting of the mitral valve, consistent with a role for filamin A in valve leaflet development.