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

Am J Hum Genet. 1997 Sep;61(3):660-7. doi: 10.1086/515496.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • DNA / blood
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / epidemiology*
  • Fragile X Syndrome / genetics
  • Genetic Testing / methods
  • Genetic Testing / psychology*
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Netherlands / epidemiology
  • Patient Participation
  • Polymerase Chain Reaction / methods
  • Prevalence
  • RNA-Binding Proteins*
  • Schools
  • Sensitivity and Specificity


  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein
  • DNA