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

Health Technology Assessment 1997; Vol. 1: No. 4Chapter 6PrevalenceStudies of prevalence fall into two distinctgroups. In one group of studies, the investigatorsstudied the cases of fragile X syndromefound in institutions. In the absence of informationon the proportion of affected individualswho are institutionalised, these studiescannot be used to estimate a population prevalence.Nonetheless, they do allow an estimateof the frequency of the disorder among individualswith mental handicap, which is usefulfor case-finding (see page 27). In a secondgroup of studies either multiple sources or asystematic method of ascertainment was usedto obtain a more complete yield of cases in thewhole of a defined population.BiasThere is likely to be marked between-studyvariability in the estimated prevalence of fragileX syndrome owing to important differences instudy design. Those studies which are basedon a cytogenetic diagnosis of fragile X syndromewill tend to yield higher estimates of prevalencethan those using DNA methods. Studies thatinclude females will tend to underestimateprevalence if diagnostic testing is restrictedto institutions and special educational units.The relatively large number of mild cases mayescape detection. Studies that include a disproportionatenumber of children will also tendto yield relatively low estimates. Diagnosis willbe delayed in individuals in whom the clinicalfeatures of fragile X syndrome are not apparentuntil puberty; indeed, in some individuals theintellectual deficit may not be noticed untilthey are of secondary school age.Frequency in thementally handicappedThe frequency of fragile X syndrome in institutionalisedmales was examined in ten studies (Table 8).Of the 2019 males tested in all the studies combined,6% were found to be affected. However, thefrequency varied greatly between studies and theheterogeneity may mean that the overall frequencyis not a reliable estimate of the true rate. TheTABLE 8 Frequency of fragile X syndrome among malesin institutions: results of ten studiesStudy Selection Number Fragile Xcriteria * (%)Finland UA 150 6 (4)Kähkönen et al, 1983Germany All 242 15 (6)Froster-Iskeniuset al, 1983USA, Boston UA 44 6 (14)Paika et al, 1984Belgium UA 354 57 (16)Fryns et al, 1984cJapan All 305 11 (4) †Arinami et al, 1986Hofstee et al, 1994UK UA 100 7 (7)Primrose et al, 1986USA, Colorado UA 267 7 (3)Hagerman et al,1988aSicily All 155 12 (8)Neri et al, 1988USA,Tennessee UA 201 4 (2)Butler & Singh, 1993Poland All 201 6 (3) †Mazurczak et al, 1996All 2019 131 (6)† All males were tested except in studies selecting those withunknown mental impairment of aetiology (UA).* Confirmed by DNA analysis.variability was due to a number of differences instudy design; viz:• admission patterns for the institution• completeness of ascertainment due topatient and parental non-compliance withdiagnostic testing• selection criteria for testing (e.g. in somestudies only those with typical features of fragileX syndrome were tested, while in otherseveryone was tested)• definition of the denominator population.21