Preconceptional and prenatal screening for fragile X syndrome: Experience with 40 000 tests

Abstract

There is now sufficient information on screening parameters and prenatal diagnosis of fragile X syndrome to offer testing to women of reproductive age.

Similar prevalence of expanded CGG repeat lengths in the fragile X mental retardation I gene among infertile women and among women with proven fertility: a prospective study

“…In two earlier observational studies, which included large cohorts of unselected women, the prevalence of premutations and full mutations during their reproductive age span was shown to vary between 1.43 24 and 0.5%, 25 whereas among women with close relatives suffering from fragile X syndrome and diagnosed with POI, the prevalence rate of the full mutation was reported to be as high as 16.8% and that of the premutation as high as 52%. 14 By contrast, among women with POI but without cases of the fragile X syndrome among close family members, the prevalence of full mutations and premutations was much lower, with the latter varying from 2.2 26 and 2.5 27 to 4.9%.…”

Carrier screening in preconception consultation in primary care

“…The number of repeats causing FXS is ≥200 (full mutation), while the 'normal' range is 6-44 repeats, and 55-200 repeats is the premutation range (i.e., carrier of FXS) (Fu et al 1991;Snow et al 1993). The length of the CGG repeat is unstable over a certain size such that a premutation can expand to a full mutation when passed onto offspring through female, but not male, carriers (Fu et al 1991;Berkenstadt et al 2007;Nolin et al 1996). Therefore, carrier screening in primary care for reproductive risk in women is more relevant as male carriers are not at risk of having children affected with FXS.…”

“…Some large-scale screening studies have found that the premutation frequency in females is 1 in 549 in Canada (Lévesque et al 2009), 1 in 158 in Israel (Berkenstadt et al 2007) and 1:179 in USA on non-selected individuals (Hantash et al 2011). Carrier frequency may be different again in other population groups, with no carriers found in 370 women screened in a Japanese study (Otsuka et al 2010) and 1,002 women from Taiwan (Huang et al 2003), although these were much smaller sample sizes.…”

“…However, guidelines from the American College of Medical Geneticists state that population carrier screening for FXS is not recommended except within well-defined clinical research protocols ) because of the difficulties around counselling and education regarding the meaning and interpretation of results (McConkie-Rosell et al 2005). Nevertheless, carrier screening for FXS does occur in clinical practice, predominantly during pregnancy, especially in Israel (Berkenstadt et al 2007;Geva et al 2000) and parts of the USA .…”

“…The majority were with pregnant women (Berkenstadt et al 2007;Cronister et al 2005;Fanos et al 2006;Huang et al 2003;Pesso et al 2000;Spence et al 1996;Ryynanen et al 1999;Toledano-Alhadef et al 2001;Kallinen et al 2001), while some included relatively smaller numbers of nonpregnant women (Pesso et al 2000;Spence et al 1996;Toledano-Alhadef et al 2001;Berkenstadt et al 2007;Geva et al 2000). Most studies essentially focused on the uptake of testing, with rates varying between 7.9% ) and 21% (Spence et al 1996) in the USA, 80% in Israel (Pesso et al 2000), and 85% (Ryynanen et al 1999) and 92% respectively in two Finnish studies (Kallinen et al 2001).…”