Abstract
OBJECTIVE: We aimed to delineate the distribution of periventricular nodular heterotopia (PNH) in patients with 22q11.2 microdeletion syndrome (22q11.2DS) and place this in the context of other genetic forms of PNH. METHODS: We retrospectively analyzed brain imaging and postmortem data available for adult patients with 22q11.2DS. We included only those with good quality MRI data (n = 29) in addition to two patients with PNH identified through postmortem studies. We also reviewed the pattern of PNH in all genetic conditions reported with this phenotype. RESULTS: Of the total seven patients (M = 4, F = 3; age: 19-61 years) identified to have PNH, six had a history of seizures, six had schizophrenia, six had variable levels of intellectual disability, and two had obsessive compulsive disorder. In all seven patients, the nodules were located over the dorsal pole of the frontal horn of the lateral ventricles. The nodules were small, noncontiguous, and ranged in number from 1 to 10 per individual. Our review identified 37 genetic conditions associated with PNH. With the cases reported here, 22q11.2DS becomes the fifth most commonly reported genetic condition, and the third most common copy number variation, associated with PNH. INTERPRETATION: The neuropsychiatric manifestations in our patients with PNH support other data indicating abnormal neurodevelopment as part of the pathogenesis of 22q11.2DS.The location and cellular characteristics of PNH in 22q11.2DS overlaps with a group of migrating postnatal interneurons termed Arc cells, although more research is needed to confirm that PNH in 22q11.2DS represents Arc cells arrested in their migratory pathway.