The Changing Face of Turner Syndrome

Abstract

Turner syndrome is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated with a wide range of clinical stigmata, such as short stature, ovarian dysgenesis, delayed puberty and infertility, congenital malformations, endocrine disorders, including a range of autoimmune conditions and type 2 diabetes and neurocognitive deficits. Morbidity and mortality is clearly increased compared with the general population and the average age at diagnosis is quite delayed. During recent years it has become clear that a multidisciplinary approach is necessary towards the patient with Turner syndrome. A number of clinical advances has been implemented, and these are reviewed. Our understanding of the genomic architecture of Turner syndrome is advancing rapidly, and these latest developments are reviewed and discussed. Several candidate genes, genomic pathways and mechanisms, including an altered transcriptome and epigenome are also presented.

Sex chromosome aneuploidies give rise to changes in the circular RNA profile: A circular transcriptome-wide study of Turner and Klinefelter syndrome across different tissues

“…Despite an incidence of one in 2,000 females for TS and one in 660 males for KS (Nielsen and Wohlert, 1991;Berglund et al, 2020), the underlying pathophysiology for both syndromes is largely unknown. Recent studies have demonstrated that changes in the transcriptome and methylome may explain part of the biological mechanisms underlying the phenotypes of sex chromosome aneuploidies (SCAs) (Sharma et al, 2015;Raznahan et al, 2018;Zhang X. et al, 2020;Gravholt et al, 2022). Based on fibroblast cell lines, peripheral blood mononuclear cells (PBMCs), amniotic fluid cells and pluripotent human cell lines, an altered expression of genes from both autosomes and sex chromosomes, in part due to global methylation changes, has been suggested in TS (Bakalov et al, 2009;Zhang et al, 2013;Massingham et al, 2014;Rajpathak et al, 2014).…”

CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome

“…Whereas misclassification would have decreased our study power and as such, our robust association of CRELD1 is likely a valid finding. We opted to include all individuals with a karyotypically-confirmed diagnosis of TS given the lack of robust karyotype-phenotype correlation in TS, and the possibility of somatic mosaicism in those with only a 45,X cell line (Gravholt et al 2022 ; Youssoufian and Pyeritz 2002 ).…”

“…Turner syndrome (TS) is a common, non-heritable genetic disorder affecting ~ 1 in 2000 females. TS is caused by a complete or partial absence of the second sex chromosome (Gravholt et al 2022 ). Individuals with TS have one or more clinical manifestations, including short stature and ovarian insufficiency.…”

“…45,X karyotype has the strongest association with CHD in TS (Fiot et al 2019 ), however, this is neither necessary nor sufficient to cause CHD in TS. Documented mosaicism with a 46,XX cell line may mitigate CHD risk (El-Mansoury et al 2007 ), but no definitive phenotype-karyotype correlations have been made with regards to CHD in TS (Gravholt et al 2022 ).…”

Turner syndrome: fertility counselling in childhood and through the reproductive lifespan

“…A small number of girls with Turner syndrome with spontaneous menarche achieve unassisted pregnancy, but most develop early secondary amenorrhea and ovarian failure. Rates of unassisted pregnancy are reported as less than 8% [1 ▪▪ ], yet a few single-centre studies have reported unassisted pregnancy rates and live birth rates as high as 13.5% [33 ▪▪ ,34] and 7.6–11.5% [33 ▪▪ ], respectively, with the preponderance seen in 45,X/46,XX karyotypes. These are obviously selected populations of girls with Turner syndrome.…”