[A large-scale diagnostic program for the fragile X syndrome among the mentally handicapped. I. An epidemiologic...

Screening for the fragile X syndrome among the mentally retarded and estimation of the prevalence of the fragile X syndrome in the Netherlands.

Descriptive.

Department of Clinical Genetics, University Hospital Dijkzigt and Erasmus University, Rotterdam, the Netherlands.

Since 1992 a screening programme for the fragile X syndrome has been conducted in 5 institutions giving residential care (1869 individuals) and 16 special schools (1483 children) in the southwestern Netherlands. After the parents/guardians' written consent, patients with an unknown cause for their mental handicap had a brief physical examination and a blood sample was taken for DNA analysis of the FMRI gene.

Among the 3352 mentally retarded individuals 2189 individuals (65%) were eligible for testing, since they had no valid diagnosis, cerebral palsy, or a previous test for the FMRI gene mutation. Of the 2189 parents/guardians 1531 (70%) 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 0.91 and specificity 0.92). The prevalence of the fragile X syndrome was estimated at 1/6045 for males (95% confidence interval: 1:9981-1:3851). On the basis of the actual number of diagnosed cases in the Netherlands, it was estimated that > 50% of the fragile X patients were undiagnosed.

The majority of parents/guardians gave consent for participation of their mentally retarded relative in the fragile X screening programme. Selection of male patients for FMRI gene analysis can be facilitated by evaluation of dysmorphic features. The calculated prevalence of the fragile X syndrome was lower than previously believed. However, the disorder was still considerably underdiagnosed.