Background: The broad spectrum of associated diseases underlying the diverse phenotypes of patients with Turner syndrome (TS) has been extensively described. However, the underlying pathophysiological mechanisms remain unknown. Few studies have analyzed congenital and acquired diseases as a function of karyotype, and conflicting results have been obtained, calling into question the role of haploinsufficiency for genes located on the X chromosome.
Objective: To investigate the effect of X chromosome gene dosage on the risk of developing congenital and acquired diseases, analysing a large database of patients with TS as a function of karyotype subgroup.
Method: Congenital and acquired diseases were evaluated in 1536 and 993 patients, respectively, and analyzed, by karyotype subgroup, at a median age of 18.9 (16.125.3) years (similar for all karyotype subgroups), in this large observational cohort study.
Results: Congenital heart and kidney malformations were more prevalent among 45X (27 vs 15%) and 45X, XrX, isoXq (25 vs 14%) patients, respectively, than among patients with mosaicism or with a Y chromosome. The cumulative incidence of acquired traits increased with age, and at 20 years, the highest prevalences were associated with isoXq for autoimmune thyroid diseases (31% (24;38)), isoXq and XrX for celiac disease (10% (617)) and isoXq, XrX and 45X for hearing loss (31% (27;35)). Lipid abnormalities were most prevalent among patients with XrX or a Y chromosome (24% (17;34)) and glucose intolerance or type 2 diabetes most prevalent among patients with XrX (12% (6;24)). Patients with XrX were more likely to have poor academic skills and those with mosaicism (45X/46XX) were more likely to display spontaneous puberty.
Conclusion: Phenotypic traits are related to karyotype in TS, highlighting the importance of the effect of gene dosage for genes located on the X chromosome. Further studies are required to determine the genetic mechanisms underlying TS pathogenesis.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology