Screening and diagnosis for the fragile X syndrome among the mentally retarded: an epidemiological and psychological survey. Collaborative Fragile X Study Group.
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.
de Vries
B B
BB
Department of Clinical Genetics, University Hospital Dijkzigt and Erasmus University, Rotterdam, the Netherlands.
van den Ouweland
A M
AM
Mohkamsing
S
S
Duivenvoorden
H J
HJ
Mol
E
E
Gelsema
K
K
van Rijn
M
M
Halley
D J
DJ
Sandkuijl
L A
LA
Oostra
B A
BA
Tibben
A
A
Niermeijer
M F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D005820:Genetic Testing / Q000379:methods / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D010358:Patient Participation; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D016601:RNA-Binding Proteins; D012574:Schools; D012680:Sensitivity and Specificity
D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human