Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study

Abstract

BackgroundKnowledge on the prevalence of sex chromosome abnormalities (SCAs) is limited, and delayed diagnosis or non-diagnosis of SCAs are a continuous concern. We aimed to investigate change over time in incidence, prevalence and age at diagnosis among Turner syndrome (TS), Klinefelter syndrome (KS), Triple X syndrome (Triple X) and Double Y syndrome (Double Y).MethodsThis study is a nationwide cohort study in a public health care system. The Danish Cytogenetic Central Registry (DCCR) holds information on all karyotypes performed in Denmark since 1961. We identified all individuals in the DCCR with a relevant SCA during 1961–2014; TS: n = 1156; KS: n = 1235; Triple X: n = 197; and Double Y: n = 287. From Statistics Denmark, which holds an extensive collection of data on the Danish population, complete data concerning dates of death and migrations in and out of Denmark were retrieved for all individuals.ResultsThe prevalence among newborns was as follows: TS: 59 per 100,000 females; KS: 57 per 100,000 males; Triple X: 11 per 100,000 females; and Double Y: 18 per 100,000 males. Compared with the expected number among newborns, all TS, 38% of KS, 13% of Triple X, and 18% of Double Y did eventually receive a diagnosis. The incidence of TS with other karyotypes than 45,X (P < 0.0001), KS (P = 0.02), and Double Y (P = 0.03) increased during the study period whereas the incidence of 45,X TS decreased (P = 0.0006). The incidence of Triple X was stable (P = 0.22).ConclusionsThe prevalence of TS is higher than previously identified, and the karyotypic composition of the TS population is changing. Non-diagnosis is extensive among KS, Triple X and Double Y, whereas all TS seem to become diagnosed. The diagnostic activity has increased among TS with other karyotypes than 45,X as well as among KS and Double Y.

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

“…Table compares crude estimates for four European countries, noting that the figures do not account for deaths, duration of study period or immigration, and are based on the total number of diagnoses in comparison to the population size. Acknowledging the differences in study design and the span of 11 years, the highest average prevalence of 40 per 100,000 was found by the Danish registry study (the highest prevalence being 59 per 100,000 of Turner syndrome during 1961–1985) (Berglund et al, ). Based on the assumption that the real prevalence of Turner syndrome is 50 per 100,000 females, Table demonstrates a considerable rate of non‐diagnosis with only 26–80% of the expected number of females with Turner syndrome diagnosed.…”

“…Based on the assumption that the real prevalence of Turner syndrome is 50 per 100,000 females, Table demonstrates a considerable rate of non‐diagnosis with only 26–80% of the expected number of females with Turner syndrome diagnosed. Furthermore, it appears that the Turner syndrome population is changing with decreases in the proportion of 45,X cases, likely due to prenatal testing followed by elective termination (Berglund et al, ).…”

Prenatal diagnosis and pregnancy determination of sex chromosome aneuploidy screened by non-invasive prenatal testing from 52,453 unselected singleton pregnancies: a retrospective analysis of 4-year experience

“…Before NIPT applied to screen fetal SCA, that the detection of SCA is usually incidental during screening for Down syndrome by conventional screening methods [22,23]. Previous studies had shown the distribution of indications for prenatal diagnosis for each SCA-affected pregnancy included ultrasonography findings( such as cystic hygroma and hydrops), advanced maternal age(≥35 years),…”

IVF and ICSI outcomes of female patients with X chromosome mosaicism: A 5-year retrospective cohort study

“…Karyotyping is widely used in the diagnosis of chromosome diseases. Aneuploidy, structure variation and mosaicism can be detected [1,2]. Double X chromosomes are essential for female [3][4][5].…”