Characteristics of periventricular nodules in patients with 22q11. 2 deletion syndrome (P2.284)

Objective: We aimed to identify the distribution of periventricular nodular heterotopia (PNH) in patients with 22q11.2 microdeletion syndrome (22q11.2DS) and its pathophysiological significance. Background: 22q11.2 microdeletion syndrome (22q11.2 DS), which encompasses phenotypes formerly known as velocardiofacial syndrome or DiGiorgio(T1) syndrome, is the most common pathological microdeletion in humans affecting 1 in 4,000 people. Although this condition has been extensively studied in the pediatric population, much less in known in adults. Neuropsychiatric disorders such as intellectual disability, seizures and schizophrenia are a significant cause of morbidity in the 22q11.2DS adult population. Design/Methods: We retrospectively analyzed brain imaging and post mortem data available for well characterized adult patients with 22q11.2DS. We included only those with good quality MRI data (n=29) and two previously reported patients with PNH identified through postmortem study. Whole genome sequencing data was available for 6 out of 7 patients. Results: Five (17.2%) of the 29 patients who met study entry criteria had observable PNH. Of the total seven subjects with PNH studied, there were five with a history of seizures, six with schizophrenia, two with obsessive compulsive disorder, and seven with variable levels of intellectual disability. In all seven patients, the nodules were located over the dorsal pole of the frontal horn of lateral ventricles. The nodules were small, non-contiguous, and varied in number from 1 to10 per subject. They were unilateral in five of the seven patients. Conclusions: The location and characteristics of PNH in 22q11.2DS patients suggest that the cells forming these PNH may belong to a recently described group of immature interneurons (termed Arc cells) that migrate during early post-natal period from the cortical subventricular zone to the cingulate and pre-frontal cortex. Possible arrested migration of such cells may contribute, at least in part, to the common neurodevelopmental disorders associated with 22q11.2DS, including intellectual disability, schizophrenia, and epilepsy. Study Supported by: Brain and behaviour foundation (DMA) Disclosure: Dr. Rezazadeh has nothing to disclose. Dr. Bercovici has nothing to disclose. Dr. Chow has nothing to disclose. Dr. Kiehl has nothing to disclose. Dr. Krings has nothing to disclose. Dr. Bassett has nothing to disclose. Dr. Andrade has nothing to disclose.