Activating germline mutations in PI3KR2 (Phosphatidylinositol 3-kinase regulatory subunit 2) have been associated with a syndrome of macrencephaly, polydactyly and Polygyria (MIM#603387), which is well described in the clinical and radiological literature not histologically. We present the first pathological description of the condition of which we are aware in a 20 week gestation fetus. Midgestation ultrasound demonstrated complex congenital heart disease, and the pregnancy was interrupted at 20 weeks gestation. Neuropathological examination demonstrated cerebral macroencephaly, with a weight greater than twice that expected for gestational age. The hemispheres were symmetrically swollen with blunted Sylvian fissures, mildly enlarged lateral ventricles and thickened cerebral mantles. Histology demonstrated leptomeningeal and subcortical heterotopia, as well as premature and abnormal neocortical lamination, principally in the frontal lobes. Cajal Retzius cells displayed enlarged Reelin (+) varicosities extending into the superficial cellular layers of the cortex, and layer II demonstrated a population of large pyramidal cells. An intracortical calretinin (+) hypocellular band was sometimes present.
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