Familial Occurrence of Congenital Anomalies of the Central Nervous System

Abstract

The pathogeneses of the majority of congenital central nervous system (CNS) anomalies have been explained from an organopathogenetic standpoint based on embryopathic (or fetopathic) findings relating to specific developmental stages. There have been, however, numerous reports from Europe and North America suggesting that genopathic or gametopathic disorders are involved in these embryopathogeneses. Perhaps because congenital CNS anomalies are not encountered in Japan as frequently as in western countries, to date no systematic or comprehensive studies of such syndromes have been published in Japan. The authors analyzed data obtained during the last 7 years from seven families in which CNS anomalies, all affecting siblings, occurred. Among this series were three cases of craniosynostosis, two of hydrocephalus, one of lissencephaly, and one of arachnoid cyst. With the exception of the arachnoid cyst, in all cases the incidence pattern suggested an hereditary mode other than X-linked. For at least three generations, only siblings had been affected; there were no documented chromosome anomalies in any other family members. In six cases of CNS anomalies there were associated chromosome anomalies, but there was no evidence that these were inherited. In this series the incidences of sibling involvement by type of anomaly were 16.7% for lissencephaly, 10.7% for craniosynostosis, 2.6% for congenital hydrocephalus, and 2.6% for arachnoid cyst. These data strongly suggest that genopathic processes are more important than gametopathic factors in the embryopathogeneses of CNS anomalies. Also, in Japan, the genetic syndromes may be relatively mild and their transmission may be predominantly autosomal recessive.