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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1997 Sep;61(3):660–667. doi: 10.1086/515496

Screening and diagnosis for the fragile X syndrome among the mentally retarded: an epidemiological and psychological survey. Collaborative Fragile X Study Group.

B B de Vries 1, A M van den Ouweland 1, S Mohkamsing 1, H J Duivenvoorden 1, E Mol 1, K Gelsema 1, M van Rijn 1, D J Halley 1, L A Sandkuijl 1, B A Oostra 1, A Tibben 1, M F Niermeijer 1
PMCID: PMC1715962  PMID: 9326332

Abstract

The fragile X syndrome is an X-linked mental retardation disorder caused by an expanded CGG repeat in the first exon of the fragile X mental retardation (FMR1) gene. Its frequency, X-linked inheritance, and consequences for relatives all prompt for diagnosis of this disorder on a large scale in all affected individuals. A screening for the fragile X syndrome has been conducted in a representative sample of 3,352 individuals in schools and institutes for the mentally retarded in the southwestern Netherlands, by use of a brief physical examination and the DNA test. The attitudes and reactions of (non)consenting parents/guardians were studied by (pre- and posttest) questionnaires. A total of 2,189 individuals (65%) were eligible for testing, since they had no valid diagnosis, cerebral palsy, or a previous test for the FMR1 gene mutation. Seventy percent (1,531/2,189) of the parents/guardians consented to testing. Besides 32 previously diagnosed fragile X patients, 11 new patients (9 males and 2 females) were diagnosed. Scoring of physical features was effective in preselection, especially for males (sensitivity .91 and specificity .92). Major motives to participate in the screening were the wish to obtain a diagnosis (82%), the hereditary implications (80%), and the support of research into mental retardation (81%). Thirty-four percent of the parents/guardians will seek additional diagnostic workup after exclusion of the fragile X syndrome. The prevalence of the fragile X syndrome was estimated at 1/ 6,045 for males (95% confidence interval 1/9,981-1/ 3,851). On the basis of the actual number of diagnosed cases in the Netherlands, it is estimated that >50% of the fragile X cases are undiagnosed at present.

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Selected References

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