Associations of Karyotype and Age at Diagnosis with Physical Features and Comorbidities in Turner Syndrome: A Single-Site Experience.

Abstract

Aim: Turner syndrome (TS) is one of the most common genetic diseases in females, with typical physical features and comorbidities. Karyotype-phenotype associations and clinical significance of childhood versus adolescent/adulthood diagnosis are conflicting.

Purpose: Determining the role of certain TS karyotypes and early (<12 years of age) vs late (≥12 years) diagnosis in TS-specific phenotype and comorbidity penetrance.

Patients and methods: Retrospective analysis of baseline characteristics and 45 TS-specific features and comorbidities of 75 TS patients were diagnosed between 2009 and 2019 and followed-up until 2023 in our tertiary care center.

Results: Thirteen different karyotypes were detected: 45,X,inv(10), 45,X,inv(9)(15), 45,X, 46,X,i(Xq), 46,X,del(Xp), 46,XX,del(X)q21, 45,X/46,X,del(X), 45,X/46,X,+mar, 45,X/46,X,rX, 45,X/46,XX, 45,X/46,XY, 45,X/47,XXX, 46,X,i(Xq)/47,XX,i(Xq). The classic karyotype with 45X monosomy showed an increased risk for hypertrichosis (28.6% vs 7.5%, OR 4.93, 95% CI [1.23-19.73]), pterygium colli (34% vs 12%, OR 3.65, 95% CI [1.13-11.75]) and short stature (91% vs 75%, OR 3.56 [0.89-14.17]. Mosaic karyotypes had a smaller risk of pterygium colli (OR 0.28 [0.073-1.092]) and short stature (OR 0.29 [0.086-1.026]. 45X/46XX mosaicism was associated with an increased risk of hypertension (33% vs 6%, OR 7.75 [1.39-43.08]), and the presence of the iso (Xq) chromosome increased the risk of celiac disease (28% vs 3%, OR 13.2 [1.52-114.52]). 44/75 (58.6%) of the cohort were diagnosed at <12 years of age. In the <12-year-old diagnosis group, facial dysmorphism and low hairline, (OR 3.30, [1.26-8.65]), low-set ears (OR 2.51 [0.98-6.46]), and breasts abnormalities (OR 4.71 [1.72-12.83]), short stature (OR 4.09 [1.13-14.82]) and GH therapy (OR 4.93 [1.31-16.01]) occurred more frequently. If diagnosed <12 years, patients had a decreased risk of hepatosplenomegaly (OR 0.10 [0.02-0.50]) and hypertension (OR 0.097 [0.01-0.85]).

Conclusion: TS patients should be handled as a heterogenous group, as they seem to differ in the penetrance of phenotypical features of the disease and the risk of comorbidities depending on karyotype and age at diagnosis.