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

Health Technology Assessment 1997; Vol. 1: No. 4Chapter 13RecommendationsThis review brings together a vast body ofliterature on fragile X syndrome. Much isnow known about the natural history, geneticsand prevalence of the disorder. The variousmeta-analyses we have performed on publishedstudies in these areas form a sound basis forhealth planners to judge whether or not thesyndrome should be considered for screening.However, when it comes to the potentialscreening strategies the position is less clear.There is considerable practical experience withactive cascade screening, particularly in NewSouth Wales. Cascade screening has been shownto be both feasible and effective in reducingaffected births within affected families; no comparabledata are available on the impact on birthprevalence for the whole population. Otheroptions have not been studied sufficiently forgeneral statements to be made about potentialscreening performance from practical experience.Nonetheless, reasonable estimates of efficacy canbe arrived at for antenatal screening. A simplemodel of the screening process suggests thatperformance could be high, and certainlycomparable with antenatal screening for Down’ssyndrome and cystic fibrosis. It is known thatinvasive prenatal diagnosis has a high acceptabilityamong carriers and that the termination rate foraffected pregnancies is high even for femalefoetuses. However, information on likely uptake islacking so it is not possible to completely predicteffectiveness. Pre-conceptual screening is completelyunevaluated but is unlikely to be a realisticoption. Paediatric screening is widely practisedbut its effectiveness is unproven, and neonatalscreening is untried.On the basis of our structured review, we make fiverecommendations for further research.1. Studies should be carried out to assess thecurrent practice of paediatric screening whenthere is developmental delay. Large numbersof samples are being sent to DNA laboratories,mainly by paediatricians, for 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 determine the variability of practicethroughout the country and whether it couldbe improved.2. There should be a national 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 normalgenetic practice. However, there is no informationon how actively this is undertaken or howsuccessful the practice is. Before the fundingof new active schemes of cascade screeningfor fragile X syndrome is considered, currentpractice needs to be evaluated.3. Research should be commissioned into thepsychosocial implications of being identifiedas having a PM. As we have emphasised,screening for fragile X syndrome has potentialhuman benefits but, for some individuals, itmay carry a high psychological price. It isimportant for this to be quantified, and aneed for research into methods of amelioratingit. This will be an important part ofany pilot studies of antenatal screening andany other screening programmes that maybe proposed.4. Pilot studies should be carried out to assessthe feasibility of routine antenatal screening.In the UK over the last 20 years, a number ofantenatal screening services have been introducedinto the NHS. Most women are nowroutinely offered maternal serum and ultrasoundscreening for neural tube defects,Down’s syndrome and a number of grossstructural abnormalities. Pilot studies ofscreening for cystic fibrosis have beensuccessfully undertaken and this serviceis beginning to be introduced. Now thatfragile X screening is technically feasible,some centres may want to add this to theirroutine practice. At present, cost will be adeterrent but, eventually, this is likely to bereduced. Well-designed pilot studies aimedat determining the practicality and acceptabilityof such testing would be of value toplanners in the future.49