Screening for Fragile X Syndrome (Murray et al.) - NIHR Journals ...
Screening for Fragile X Syndrome (Murray et al.) - NIHR Journals ...
Screening for Fragile X Syndrome (Murray et al.) - NIHR Journals ...
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He<strong>al</strong>th Technology Assessment 1997; Vol. 1: No. 4Chapter 9Practic<strong>al</strong> experience of screeningand diagnosisAntenat<strong>al</strong> screeningThere have not y<strong>et</strong> been any large-sc<strong>al</strong>e,population-based screening programmes inthe gener<strong>al</strong> population. However, there issome in<strong>for</strong>mation from two studies in whichattempts to screen selected populations havebeen made.Fairfax, USAA pilot study was initiated at the end of 1993.All women referred to a gen<strong>et</strong>ics institute <strong>for</strong>prenat<strong>al</strong> diagnosis were offered screening ona self-pay basis (Howard-Peebles <strong>et</strong> <strong>al</strong>, 1995;Spence <strong>et</strong> <strong>al</strong>, 1996). The princip<strong>al</strong> reason<strong>for</strong> referr<strong>al</strong> was advanced reproductive age.A tot<strong>al</strong> of 3345 pregnant women were offeredthe test, of whom 688 (21%) accepted. A largeproportion (31%) of those accepting the offerhad a family history of ment<strong>al</strong> r<strong>et</strong>ardation,learning disability, autism or attention-deficitdisorders, which may have influenced theirdecision. Of the three women who werefound to have a PM, <strong>al</strong>l had an unremarkablefamily history.New York, USAA sm<strong>al</strong>l antenat<strong>al</strong> screening programme hasbeen in place since 1992 <strong>for</strong> women with a familyhistory of learning disability of unknown a<strong>et</strong>iology(Brown <strong>et</strong> <strong>al</strong>, 1996). Some 344 women have beenscreened, but no in<strong>for</strong>mation is available on thenumber being offered the test. Six women werefound to have FMR-1 mutations – two had an FMand four a PM.Pre-conceptu<strong>al</strong> screeningThere are no reported studies of screening lowrisk populations prior to pregnancy. However,one centre has reported on testing 271 potenti<strong>al</strong>egg donors in an in-vitro fertilisation programme(Spence <strong>et</strong> <strong>al</strong>, 1996). One woman was found tohave a PM and another produced a result in thegrey zone, with a repeat size of 52. Both womenwere counselled and offered prenat<strong>al</strong> diagnosisin a subsequent pregnancy.Active cascade screeningThree fully active screening programmes havebeen reported so far; a fourth did not start bycase-finding among the ment<strong>al</strong>ly-handicappedbut used cytogen<strong>et</strong>ic records as its basis, tog<strong>et</strong>herwith an education<strong>al</strong> campaign among he<strong>al</strong>thcare providers.New South W<strong>al</strong>es,Austr<strong>al</strong>iaA state-wide screening programme has grown outof the studies aimed at case-finding which werestarted more than 10 years ago in New South W<strong>al</strong>es,Austr<strong>al</strong>ia (Turner <strong>et</strong> <strong>al</strong>, 1986). Over the years theproject has become a full-sc<strong>al</strong>e cascade screeningprogramme, whose stated aim is to in<strong>for</strong>mextended families about the reproductive risksbe<strong>for</strong>e childbearing.By 1990, the clinic<strong>al</strong> history of over 14,000intellectu<strong>al</strong>ly-handicapped individu<strong>al</strong>s, adultsand schoolchildren, had been reviewed and justover h<strong>al</strong>f were selected <strong>for</strong> testing (Turner <strong>et</strong> <strong>al</strong>,1992). Permission to test was received from79%, which resulted in 253 putative cases beingidentified, 30% of whom were not <strong>al</strong>ready knownto have fragile X syndrome. (Subsequent DNAtesting showed that some of these were f<strong>al</strong>sepositivediagnoses).A case-control study has been carried out toexamine the influence of gen<strong>et</strong>ic counsellingon subsequent reproduction among fem<strong>al</strong>eFM and PM carriers identified in the early stagesof the scheme. In 303 case-control pairs, thosegiven counselling had 26% fewer pregnancies(77 versus 104). This reproductive decline wasmost marked in the 85 pairs of women who<strong>al</strong>ready had an affected child; there were 70%fewer pregnancies (six versus 20). There were77 pregnancies in the women who had beencounselled, and <strong>al</strong>though prenat<strong>al</strong> diagnosiswas offered, only 61% accepted. Since theintroduction of DNA testing m<strong>et</strong>hods, 44 fem<strong>al</strong>ecarriers identified by the scheme have subsequentlybecame pregnant (Robinson <strong>et</strong> <strong>al</strong>, 1996).All were offered prenat<strong>al</strong> diagnosis and 34(77%) accepted.33