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

Health Technology Assessment 1997; Vol. 1: No. 4Chapter 5DefinitionsInterpreting the literature on fragile X syndromeis complicated by variable and changing usageof the terms affected, carrier and screening. Forthe purposes of this review, explicit definitionsare used in an attempt to avoid ambiguity in theconclusions and recommendations.AffectedStudies vary in the extent to which individualswith a normal phenotype but a genetic lesionare regarded as affected. Males do not constitutea problem as the clinical, cytogeneticand DNA diagnosis is likely to coincide butthis is not the case for females (see page 13).In this review, we have restricted the termaffected to individuals with the fragile Xsyndrome phenotype.CarrierBefore the introduction of DNA testing that wascapable of distinguishing females with an FM orPM, the term carrier was used ambiguously. Womenwho were phenotypically normal mothers ofaffected individuals or who themselves had fragileX syndrome were classified together as obligatecarriers. Other family members may only havebeen classified as carriers if this could be demonstratedcytogenetically. In this review we havetried to avoid the term carrier; however, whereits use was deemed necessary it is prefixed byPM or FM, and in FM carriers we distinguishbetween those with and without clinical fragileX syndrome by referring to affected andunaffected carriers, respectively.Screening for fragile X syndromeIn common usage, screening includes any kindof testing carried out to detect a disorder. This istoo vague a concept for public health purposes,where four aspects of the screening process needemphasis. These are that• it is routine and systematic• it is applied to apparently healthy individuals• it aims to select those who are at high risk ofa well defined disease• those in the high risk group are offered provenpreventive action which would be too expensiveor hazardous for general use.Sometimes fragile X testing is carried out onindividuals with learning disabilities in order toimprove or confirm a clinical diagnosis. Thisis not screening. However, if such a populationis systematically tested it might be regarded asscreening, depending on the intention. If theaim is simply case-finding, for example, in orderto provide an estimate of prevalence, this wouldnot be considered screening. If, however, theendpoint of the case-finding is preventive, sayas the starting point of a systematic attempt toidentify affected families for counselling ortesting, then it would be considered as partof a screening programme.19