A systematic cytogenetic study of a population of 1170 mentally retarded and/or behaviourly disturbed patients including fragile X-screening. The Hondsberg experience.

Abstract

A cytogenetic study was performed in a population of 1170 mentally retarded and/or behaviourly disturbed patients of the Hondsberg Institute in the south of the Netherlands. The cytogenetic data are presented and discussed. In all patients chromosomal evaluation was performed with Giemsa-banding and Quinacrine fluorescence, and additional banding techniques were performed whenever they were necessary to clarify the chromosomal abnormality. A fragile X screening with M199 cultures was performed in 311 males. In 22.1% of the patients a chromosomal basis was found for their developmental retardation: 14.3% Down syndrome patients, 6.1% other chromosomal abnormalities (mainly partial autosomal trisomies and monosomies and sex-chromosome abnormalities). In 24 males, through 21 index patients, a positive fragile X screening was found, i.e. 6.7% of the screened population and 1.8% of the total population. These results indicate that the diagnostic contribution of the fragile X screening is numerically of equal importance as are advanced chromosome banding techniques, and its contribution to the diagnosis of fragile X syndrome in one index male patient in general leads to the detection of several female relatives at risk to be carrier of this X-linked recessively inherited condition. The causal relationship between the occurrence of mental retardation and chromosomal aberration in genera i.e. autosomal trisomies, partial autosomal trisomies and monosomies, and Xq27-28 fragility is well established and is, to some extent, easy to understand. Whether carriers of other chromosomal rearrangements, mainly of balanced reciprocal and Robertsonian translocations, small extra chromosomes, paracentric inversions and chromosomal variants, have increased risk for mental handicap and/or congenital malformations in their progeny, remains unclear at the present time. Some of these residual problems and questions are discussed in the perspective of their importance for genetic counseling. Detailed data will be presented about the mental development and psychological profile of patients with these different types of chromosomal abnormalities and rearrangements.