The comorbidity landscape of 47,XXX syndrome: A nationwide epidemiologic study

Genet Med. 2022 Feb;24(2):475-487. doi: 10.1016/j.gim.2021.10.012. Epub 2021 Nov 30.


Purpose: This study aimed to describe the comorbidity pattern in 47,XXX syndrome.

Methods: This was a registry-based study of hospital diagnoses and prescribed medication in a nationwide cohort of females with 47,XXX (n = 103) and 46,XX/47,XXX (n = 57) in which they were compared with 16,000 age-matched general population female controls.

Results: The overall occurrence of hospital diagnoses was significantly increased in females with 47,XXX when compared with controls (incidence rate ratio = 2.1, CI = 1.7-2.5), and when divided into 19 organ-specific groups, there was a significantly increased risk in the following 14 groups: infection, blood, endocrine and metabolism, mental, nervous system, eye, ear, respiratory, oral cavity and gastrointestinal, musculoskeletal, perinatal, congenital malformations, external factors, and "other." The risk of being prescribed any medication was not significantly increased in females with 47,XXX when compared with controls (hazard ratio = 1.2, CI = 0.9-1.4). However, when stratified according to medication groups, a significantly increased risk was detected in 4 of 13 groups. The overall occurrence of hospital diagnoses was also significantly increased when females with 46,XX/47,XXX were compared with controls (incidence risk ratio = 1.3, CI = 1.01-1.8), but generally, in comparison with controls, females with 46,XX/47,XXX were less severely affected than females with 47,XXX.

Conclusion: The 47,XXX syndrome is associated with an increased occurrence of a wide variety of diseases. Increased awareness of this may contribute to improve counseling and clinical assessment of these patients.

Keywords: 46,XX/47,XXX; 47,XXX; Triple X syndrome; Trisomy X.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, X
  • Comorbidity
  • Epidemiologic Studies
  • Female
  • Humans
  • Pregnancy
  • Sex Chromosome Aberrations*
  • Sex Chromosome Disorders of Sex Development* / diagnosis
  • Trisomy

Supplementary concepts

  • Triple X syndrome