Incidence of Fragile X syndrome in Ireland

Abstract

Described as the commonest single gene cause of learning disability internationally, the incidence of Fragile X syndrome (FXS) has never previously been determined in Ireland. The aim of this work was to determine the observed incidence of FXS in the island of Ireland; the Republic of Ireland (ROI) and Northern Ireland (NI) separately and combined. Ascertainment was achieved for a cross-sectional study by a retrospective, clinical and laboratory database review of positive FXS cases, born in either ROI or NI, between years 2000-2009 inclusive. The observed incidence of FXS per 10,000 live births in the island of Ireland in males was 0.94 (95%CI: 0.75-1.13) or ∼1:10,600 and in females was 0.23 (95%CI: 0.14-0.32) or ∼1:43,000. Comparable testing rates for FXS are present in ROI and NI, with on average 1.48% (1.30% in ROI, 1.96% in NI) of live male births and 0.4% (0.35% in ROI, 0.55% in NI) of live female births undergoing analysis which is comparable to other centres internationally. This study demonstrates the observed incidence of FXS in the island of Ireland is (i) approximately half the estimated worldwide incidence in males and is not explained by low levels of testing, and (ii) approximately one quarter the estimated worldwide incidence in females which may be explained by low levels of testing. © 2017 Wiley Periodicals, Inc.

Fragile X syndrome and fragile X-associated disorders

“…The frequency of expanded FMR1 alleles varies globally because of both founder effects and racial differences in haplotypes that may predispose individuals in certain regions of the world to CGG expansions 43 . Recently, the highest prevalence of expanded alleles has been reported in Ricuarte, a small town in Colombia 4 .…”

“…In sharp contrast to Ricuarte is Ireland, which has extremely low rates of prevalence of the full mutation: 1:10,619 males and 1:43,540 females. Researchers in Ireland speculate that a lineage-specific haplotype is responsible for this low incidence 43 . China also has a relatively low reported incidence of FXS; however, owing to a gap between China and Western countries regarding FXS awareness, it is likely that a significant number of potential patients with FXS in China have been misdiagnosed or underdiagnosed 6 .…”

Symptomatic Mandibular Fibrous Dysplasia With Concurrent Triple X- and Premutation Stage Fragile-X-Syndrome: Case Report With Short Literature Survey

“…The phenotype was already known from clinical studies (24) and is also known under the eponym Martin-Bell syndrome (25). FXS occurs in men and women, with lower frequency in males (26). Pathfinding symptoms of diagnosis are attentiondeficit/hyperactivity disorders and learning disabilities (27,28).…”