X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood

Objective Turner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup. Design and methods This national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87). Results Median age was 9.4 (3.7–13.7) years at first evaluation and 16.8 (11.2–21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P