Revisiting the Neuropsychological and Clinical Profile of Mosaic Turner Syndrome With a Ring X Chromosome

Determining karyotype-phenotype correlations for individuals with Turner syndrome ("TS individuals") is a longstanding research endeavor. The limited literature on Turner syndrome (TS) with a ring X chromosome hinders counseling about the neuropsychological and clinical features. To further characterize these phenotypes, we compared 27 TS individuals with 46,X,r(X)/45,X ("ring X") to 50 non-mosaic 45,X, and 27 mosaic 45,X/46,XX ("mosaic 45,X") individuals. This retrospective cohort study of 104 individuals reported on cardiac and renal malformations, endocrine and neuropsychological conditions, and applied contemporary terminology in a nuanced framework to assess intellectual developmental disorder (IDD). We noted an increased IDD risk for TS individuals with ring X compared to mosaic 45,X and non-mosaic 45,X, though at a lower frequency (26%, 6 of 23) than previously reported. Across karyotypes, 49% (16 of 33) of TS individuals with neuropsychological evaluations had a diagnosis of other specified neurodevelopmental disorder due to TS. In TS individuals with ring X, there was an increased risk for hypothyroidism, whereas bicuspid aortic valve and horseshoe kidney were less frequent compared to other karyotypes. These results add to the limited literature on TS individuals with ring X and can inform the counseling of TS individuals, caregivers, and expectant parents.