Screening for Fragile X Syndrome (Murray et al.) - NIHR Journals ...

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PrevalenceGeneral population prevalenceIn seven studies, attempts have been made toestimate the population prevalence of fragileX syndrome in males (see Table 9). The usualapproach was to carry out diagnostic tests onyoung people with special educational needs.The number of individuals found to be affectedwas then related to the size of the population ofthe same age from which they were drawn. Sincetesting was not acceptable to all subjects, the figureswere generally adjusted upwards proportionally onthe assumption that there was no bias in the thoseaccepting testing. This may not be a valid assumptionas, in one study (Tranebjaerg et al, 1994), therate of acceptance was higher in those individualswith severe learning disabilities than in those withmilder symptoms. One of the studies was based ona cytogenetic register. Of the studies using schoolpopulations, one relied solely on special schoolsbut, for the age range studied, it is unlikely thatmany boys with the disorder would be inmainstream education.The results from each of the seven studies are shownin Table 9. The study based on a register yielded aparticularly low prevalence but it is unclear howcomplete the register was. The studies of youngpeople using a cytogenetic technique for diagnosisyielded much higher prevalence estimates thanthe remainder. This is likely to reflect the knowntendency for cytogenetics to produce false-positiveresults. Of the four studies using DNA methods ofdiagnosis, two had originally been based on cytogeneticsbut were subsequently updated. The cytogenetically-basedfigures for these studies have beenwidely quoted but, when those with positive resultswere DNA tested, it became clear that these weregross overestimates. In the Australian study, four ofthose originally believed to have fragile X syndromecould be excluded, thus reducing the observedprevalence from 3.8 (Turner et al, 1986) to 2.3per 10,000 males (Turner et al, 1996). In the UK –Coventry study, DNA analysis has enabled thereclassification of ten patients diagnosed with fragileX syndrome in the original cytogenetic study. Thus,the original prevalence of 10.5 per 10,000 boys(Webb et al, 1986b) has been reduced to 2.4 per10,000 (Morton et al, 1997). Only one study wascompletely based on DNA techniques (Jacobset al, 1993) and this yielded a prevalence of 2.6per 10,000 in males.Taking all the DNA studies together, the combinedprevalence is about 2.5 per 10,000 males or 1 in4000. From what information is available, this mustbe regarded as the best estimate of populationprevalence. However, it should be regarded as aminimum estimate since, in general, boys wereonly tested if they were at state schools. In theTABLE 9 Population prevalence of fragile X syndrome in males: results from seven studiesStudy Diagnostic Age range Source of Number Fragile X syndrometechnique * (years) samples † testedNumber Rate per 10,000Sweden CG < 18 PD 89 12 5.9Gustavson et al, 1986Finland CG 8–9 MS 61 4 8.3Kähkönen et al, 1987Denmark CG All CR 31 31 0.4Tranebjaerg et al, 1994UK,Wessex I DNA 5–18 MS 180 4 2.8Jacobs et al, 1993UK,Wessex II DNA 5–18 MS 1013 5 2.0Murray et al, 1996UK, Coventry CG/DNA 11–16 SS 219 6 2.4Morton et al, 1997Australia CG/DNA 5–18 SS & MS 472 10 3.0Turner et al, 199622* CG, cytogenetic method; DNA, DNA method; CG/DNA, cytogenetic method originally, but positives later re-analysed usingDNA method.† PD, individuals identified from paediatric records; MS, those with mental handicap in mainstream schools; SS, from special schools;CR, from cytogenetics register.
Health Technology Assessment 1997; Vol. 1: No. 4Australian study it was thought that a large numberof children may have been excluded because theywere at private schools (Turner et al, 1992). Fourof the studies also considered the prevalence offragile X syndrome in females. In the UK – Wessexstudies, an estimate was not possible as no caseswere found in the 74 girls tested (Jacobs et al,1993), but in the other three studies the prevalencewas about half of that found in males (Kähkönenet al, 1987; Webb et al, 1986b; Turner et al, 1986).23
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