Human and financi<strong>al</strong> costs of screeninggen<strong>et</strong>ic screening. The NHS Centr<strong>al</strong> R&DCommittee (1995) has endorsed this report andraised its own concerns. The Committee expressedthe view that gen<strong>et</strong>ics differs from other biomedic<strong>al</strong>areas in that it involves not only theindividu<strong>al</strong> being tested but <strong>al</strong>so other familymembers. The Department of Trade and Industry(1996), in response to a report of the Houseof Commons Select Committee on Science andTechnology, has advised the Government toestablish an Advisory Committee on Gen<strong>et</strong>icTesting. This committee has now been established(chaired by Professor Polkinghorne) and it islikely that the Department of He<strong>al</strong>th will seekits <strong>et</strong>hic<strong>al</strong> advice should screening <strong>for</strong> fragileX syndrome be seriously considered.48
He<strong>al</strong>th Technology Assessment 1997; Vol. 1: No. 4Chapter 13RecommendationsThis review brings tog<strong>et</strong>her a vast body ofliterature on fragile X syndrome. Much isnow known about the natur<strong>al</strong> history, gen<strong>et</strong>icsand prev<strong>al</strong>ence of the disorder. The variousm<strong>et</strong>a-an<strong>al</strong>yses we have per<strong>for</strong>med on publishedstudies in these areas <strong>for</strong>m a sound basis <strong>for</strong>he<strong>al</strong>th planners to judge wh<strong>et</strong>her or not thesyndrome should be considered <strong>for</strong> screening.However, when it comes to the potenti<strong>al</strong>screening strategies the position is less clear.There is considerable practic<strong>al</strong> experience withactive cascade screening, particularly in NewSouth W<strong>al</strong>es. Cascade screening has been shownto be both feasible and effective in reducingaffected births within affected families; no comparabledata are available on the impact on birthprev<strong>al</strong>ence <strong>for</strong> the whole population. Otheroptions have not been studied sufficiently <strong>for</strong>gener<strong>al</strong> statements to be made about potenti<strong>al</strong>screening per<strong>for</strong>mance from practic<strong>al</strong> experience.Non<strong>et</strong>heless, reasonable estimates of efficacy canbe arrived at <strong>for</strong> antenat<strong>al</strong> screening. A simplemodel of the screening process suggests thatper<strong>for</strong>mance could be high, and certainlycomparable with antenat<strong>al</strong> screening <strong>for</strong> Down’ssyndrome and cystic fibrosis. It is known thatinvasive prenat<strong>al</strong> diagnosis has a high acceptabilityamong carriers and that the termination rate <strong>for</strong>affected pregnancies is high even <strong>for</strong> fem<strong>al</strong>efo<strong>et</strong>uses. However, in<strong>for</strong>mation on likely uptake islacking so it is not possible to compl<strong>et</strong>ely predicteffectiveness. Pre-conceptu<strong>al</strong> screening is compl<strong>et</strong>elyunev<strong>al</strong>uated but is unlikely to be a re<strong>al</strong>isticoption. Paediatric screening is widely practisedbut its effectiveness is unproven, and neonat<strong>al</strong>screening is untried.On the basis of our structured review, we make fiverecommendations <strong>for</strong> further research.1. Studies should be carried out to assess thecurrent practice of paediatric screening whenthere is development<strong>al</strong> delay. Large numbersof samples are being sent to DNA laboratories,mainly by paediatricians, <strong>for</strong> fragile X diagnosis.The percentage yield of cases is notvery high, and it might be more efficient topreselect samples so that only those with thehighest risk of the disorder are tested. A surveythat includes a large number of laboratories isneeded to d<strong>et</strong>ermine the variability of practic<strong>et</strong>hroughout the country and wh<strong>et</strong>her it couldbe improved.2. There should be a nation<strong>al</strong> audit of currentpractice in cascade screening of affectedfamilies. Cascade screening must be regardedas of proven benefit and, in this country, it iscarried out to some extent as part of norm<strong>al</strong>gen<strong>et</strong>ic practice. However, there is no in<strong>for</strong>mationon how actively this is undertaken or howsuccessful the practice is. Be<strong>for</strong>e the fundingof new active schemes of cascade screening<strong>for</strong> fragile X syndrome is considered, currentpractice needs to be ev<strong>al</strong>uated.3. Research should be commissioned into thepsychosoci<strong>al</strong> implications of being identifiedas having a PM. As we have emphasised,screening <strong>for</strong> fragile X syndrome has potenti<strong>al</strong>human benefits but, <strong>for</strong> some individu<strong>al</strong>s, itmay carry a high psychologic<strong>al</strong> price. It isimportant <strong>for</strong> this to be quantified, and aneed <strong>for</strong> research into m<strong>et</strong>hods of amelioratingit. This will be an important part ofany pilot studies of antenat<strong>al</strong> screening andany other screening programmes that maybe proposed.4. Pilot studies should be carried out to assessthe feasibility of routine antenat<strong>al</strong> screening.In the UK over the last 20 years, a number ofantenat<strong>al</strong> screening services have been introducedinto the NHS. Most women are nowroutinely offered matern<strong>al</strong> serum and ultrasoundscreening <strong>for</strong> neur<strong>al</strong> tube defects,Down’s syndrome and a number of grossstructur<strong>al</strong> abnorm<strong>al</strong>ities. Pilot studies ofscreening <strong>for</strong> cystic fibrosis have beensuccessfully undertaken and this serviceis beginning to be introduced. Now thatfragile X screening is technic<strong>al</strong>ly feasible,some centres may want to add this to theirroutine practice. At present, cost will be ad<strong>et</strong>errent but, eventu<strong>al</strong>ly, this is likely to bereduced. Well-designed pilot studies aimedat d<strong>et</strong>ermining the practic<strong>al</strong>ity and acceptabilityof such testing would be of v<strong>al</strong>ue toplanners in the future.49
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