DO: 0050561;
Nokelainen et al. (2001) described 2 brothers, aged 9 and 11 years, with severe mental retardation of unknown origin who shared several physical anomalies including large round head, small concave nose, downslanted palpebral fissures, and gingival hyperplasia. In addition to relative macrocephaly, magnetic resonance imaging showed severe cerebral atrophy, especially in the frontotemporal regions. The brothers also had a thin corpus callosum and atrophic caudate nuclei. The reduced white matter showed patchy periventricular signal intensity changes. The lateral and third ventricles were large, and the fourth ventricle was of normal size. The boys had large cisterna magna, communicating widely with the fourth ventricle, but no vermian hypoplasia. Both boys had Lennox-Gastaut spectrum type epilepsy. No chromosomal anomalies were found. Some of the clinical findings resembled fetal alcohol effects/fetal alcohol syndrome, which was also suggested by history. The severe epilepsy in the brothers was of multiple seizure type (especially myoclonic), necessitating polytherapy. Nokelainen et al. (2001) suggested that these brothers had an unidentified inherited syndrome, possibly modified by fetal alcohol exposure, which they referred to as an inherited encephalopathy. The extent of the exposure to alcohol was not detailed; however, it was thought that many of the features were not explained by fetal alcohol syndrome, including macrocephaly. The disease had progressed slowly during the first decade of life. The patients were Finnish, but none of the features satisfied those of any of the identified 'Finnish diseases.'
Nokelainen, P., Heiskala, H., Raininko, R., Autti, T., Wirtavuori, K., Hakkinen, A.-M., Flint, J. 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? Am. J. Med. Genet. 103: 198-206, 2001. [PubMed: 11745991] [Full Text: https://doi.org/10.1002/ajmg.1536.abs]