Left-sided congenital heart lesions in mosaic Turner syndrome

Abstract

In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

Haplotype analysis of the X chromosome in patients with Turner syndrome in order to verify the possible effect of imprinting on selected symptoms

“…The most common of these are the bicuspid aortic valve -almost 30% -and aortic coarctation in approximately 12% of women with TS. Very often, we also encounter hypoplasia of the left heart and anomalies of the pulmonary veins 4,[8][9][10] .…”

Clinical, cytogenetic, and molecular findings of isodicentric Y chromosomes

“…A few researchers found a potential correlation between isodicentric Y chromosomes and susceptibility to schizophrenia [58], but the evidence was not strong enough [59]. There are some other rare defects that occur in patients carrying isodicentric Y chromosomes, such as Moyamoya disease, aortic dissection, and congenital heart disease [18, 35, 60, 61]. These are either coincidences or consequences of the altered dosage of sex chromosome genes [60, 61].…”

“…There are some other rare defects that occur in patients carrying isodicentric Y chromosomes, such as Moyamoya disease, aortic dissection, and congenital heart disease [18, 35, 60, 61]. These are either coincidences or consequences of the altered dosage of sex chromosome genes [60, 61]. Individual differences in development also play a vital role in the clinical manifestations of patients [62–64].…”

A Systematic Review of Acute Thoracic Aortic Dissections in Africa—The Need for a Registry

“…There were 20 case reports or case series. 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43…”