Analysis of neocortex in three males with the fragile X syndrome

TLDR

Fragile X syndrome is a common hereditary disorder marked by a fragile site at Xq27.3 and presenting clinically as mental retardation. The study examined neocortical intra‑layer cell density by counting cresyl violet‑stained neurons in 10 random fields of layers II–VI in Brodmann areas 23 and 38 of cingulate and temporal association cortices in three affected males. Postmortem analysis of three fragile X males revealed no gross neuropathology, preserved neuronal density, but abnormal dendritic spine morphology—immature, long, tortuous spines—consistent across cases, indicating that dendritic abnormalities characterize the neocortex in this form of mental retardation.

Abstract

Abstract Fragile X [fraX] syndrome is a common hereditary disorder associated with a fragile site marker at Xq27.3 which clinically presents as a form of mental retardation (MR). Postmortem investigation of 3 fraX positive males with mild to moderate MR did not document any gross neuropathological changes. Golgi analysis of neocortical dendritic spine morphology extended our previous observations of immature, long, tortuous spines in one adult case of fraX (Rudelli, et al., Acta Neuropathologica 67:289–295, 1985) to 2 new cases. Evidence for similar dendritic spine abnormalities was found, although Golgi analysis was less than optimal because of incomplete dendritic stain impregnation. Neocortical intra‐layer cell density was also investigated in all 3 cases. Cresyl violet stained neurons were counted in 10 randomly selected fields in neocortical layers II–VI of cingulate and temporal association areas (Brodmann's areas 23 and 38). Neuron counts in fraX and control neocortex showed no significant differences. Thus, abnormal dendritic spine morphology with preservation of neuronal density appears to characterize the neocortex in individuals with this common form of mental retardation.