Mosaic Turner syndrome shows reduced penetrance in an adult population study

Purpose: Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the penetrance has been overestimated. Methods: We characterized the prevalence and phenotypic consequences of X chromosome aneuploidy in a population of 244,848 women over 40 years of age from UK Biobank, using single-nucleotide polymorphism (SNP) array data. Results: We detected 30 women with 45, X; 186 with mosaic 45, X/46, XX; and 110 with 47, XXX. The prevalence of nonmosaic 45, X (12/100,000) and 47, XXX (45/100,000) was lower than expected, but was higher for mosaic 45, X/46, XX (76/100,000). The characteristics of women with 45, X were consistent with the characteristics of a clinically recognized Turner syndrome phenotype, including short stature and primary amenorrhea. In contrast, women with mosaic 45, X/46, XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. The phenotype of women with 47, XXX included taller stature (5.3 cm; SD = 5.52 cm; P = 5.8 x 10(-20)) and earlier menopause age (5.12 years; SD = 5.1 years; P = 1.2 x 10(-14)). Conclusion: Our results suggest that the clinical management of women with 45, X/46, XX mosaicism should be minimal, particularly those identified incidentally.