Two brothers with macrocephaly, progressive cerebral atrophy and abnormal white matter, severe mental retardation, and Lennox-Gastaut spectrum type epilepsy: An inherited encephalopathy of childhood?

Two brothers with severe mental retardation of unknown origin were found to share several physical anomalies, including large round head, small concav e nose, down-slanted palpebral fissures, and gingival hyperplasia. In addit ion to relative macrocephaly, magnetic resonance imaging (MRI) showed sever e cerebral atrophy, especially fronto-temporally. The brothers also had a t hin corpus callosum and atrophic caudate nuclei. The reduced white matter s howed patchy periventricular signal intensity changes. The lateral and thir d ventricles were large, but the fourth ventricle was of normal size. The b oys had large cisterna magna, communicating widely with the fourth ventricl e, but no vermian hypoplasia. Both boys had Lennox-Gastaut spectrum type ep ilepsy. No chromosomal anomalies were found, despite the suggestive clinica l picture. Some of the clinical findings resembled fetal alcohol effects/fe tal alcohol syndrome (FAE/FAS), which was also suggested by history. Curren t diagnostic criteria for FAE/FAS, however, excluded full-blown FAS in thes e cases and failed to explain the entire clinical picture in the boys. We a rgue that these boys had an unidentified inherited syndrome, possibly modif ied by fetal alcohol exposure. (C) 2001 Wiley-Liss, Inc.