Karyotype-phenotype associations in turner syndrome: a multicenter retrospective cohort study

Establishing clear links between different Turner syndrome (TS) karyotypes and phenotypes would help inform discussions around likely disease trajectories. Here we explored associations between karyotype, clinical features, and growth hormone (GH) responses in individuals with TS.

This was a retrospective observational study of 86 patients diagnosed with TS attending three endocrine centers in Abu Dhabi, UAE. Clinical and genetic data were retrieved from the medical records. Changes in height standard deviation score (SDS) over time were assessed with repeated measured ANOVA with Tukey's post hoc test.

The median (IQR) age of participants at diagnosis was 9.3 (6.5, 13.4) years. 44.2% were classical monosomies, 18.6% were mosaic, and 37.2% were structural X-chromosome abnormalities (isochromosome Xq, deletions, ring chromosome). GH treatment was started at a mean (SD) of 8.7 (4.0) years, which resulted in a significant increase in mean (SD) height SDS, with a greater increase in the first year [0.59 (0.13)] than between years 1 and 3 [0.22 (0.13)]. Spontaneous menarche occurred in 1/23 (4.3%) of evaluable 45, X individuals, compared with 6/12 (50.0%) of mosaic and 10/22 (45.5%) of structural X-chromosome abnormality cases (p=0.002), and autoimmune hypothyroidism was significantly more common in individuals with structural X-chromosome abnormalities (15/32, 46.9%, vs 5/37, 13.5%, and 1/16, 6.2%, in monosomy and mosaic cases, respectively; p<0.001; adjusted OR 5.22 [95% CI 1.55-17.53] after adjustment for current age). No detectable association was observed between karyotype and one-year GH response in the available analyses.

TS remains challenging to recognize and manage, and early detection and management are crucial to optimize growth, pubertal development, and quality of life. Knowledge of karyotype-phenotype associations helps to manage patient and family expectations and plan likely future management.