Morbidity, mortality, and socioeconomics in Klinefelter syndrome and 47,XYY syndrome: a comparative review

Abstract

Context Klinefelter syndrome (KS, 47,XXY) and 47,XYY syndrome are genetic conditions characterized by a supernumerary sex chromosome. The conditions share many traits, but considerable phenotypic differences are seen between the two. Focusing on morbidity, mortality, and socioeconomics, this review highlights similarities and differences. Methods Relevant literature was identified through PubMed with the following search terms; 'Klinefelter', '47,XXY', '47,XYY', and 'Jacobs syndrome'. Included journal articles were chosen at the authors’ discretion. Results KS and 47,XYY are the most common sex chromosome disorders in males, with an expected prevalence of 152 and 98 per 100,000 newborn males, respectively. Non-diagnosis is extensive, as only about 38% of KS and 18% of 47,XYY are diagnosed. Both conditions are associated with an increased mortality risk and increased risk of a variety of diseases and other health-related problems affecting virtually every organ system. Early diagnosis seems to predict a lesser comorbidity burden. Neurocognitive deficits as well as social and behavioral problems are commonly described. Both syndromes are associated with poor socioeconomicfor example, lower income and educational level and higher rates of crime. Infertility is a hallmark of KS, but fertility seems also reduced in 47,XYY. Conclusion Being born as a boy with an extra X or Y chromosome is associated with increased mortality and excess morbidity, partially expressed in a sex chromosome-specific pattern.Both syndromes continue to be greatly underdiagnosed, even thoughearly intervention may improve the overall outcome. Earlier diagnosis to initiate timely counseling and treatment should be emphasized.

Prevalence, Morbidity, and Mortality of Men With Sex Chromosome Aneuploidy in the Million Veteran Program Cohort

“…Our results corroborate findings from multiple other studies that associate SCAs with excess morbidity and higher health care utilization . Men with 47,XXY, independent of a known clinical diagnosis, were more likely than controls to endorse a history of numerous medical and psychological conditions, most of which have been previously reported and serve as external validation of our results .…”

“…Our results corroborate findings from multiple other studies that associate SCAs with excess morbidity and higher health care utilization . Men with 47,XXY, independent of a known clinical diagnosis, were more likely than controls to endorse a history of numerous medical and psychological conditions, most of which have been previously reported and serve as external validation of our results . We also observed worse self-reported health and well-being metrics among men with SCA, which is congruent with current research, in which lower QOL outcomes are widely reported in individuals with SCAs .…”

“…2,4,6 Men with 47,XXY, independent of a known clinical diagnosis, were more likely than controls to endorse a history of numerous medical and psychological conditions, most of which have been previously reported and serve as external validation of our results. [2][3][4][5][6][7][8] We also observed worse self-reported health and well-being metrics among men with SCA, which is congruent with current research, in which lower QOL outcomes are widely reported in individuals with SCAs. 8,31,32 In contrast, we did not find greater mortality, 3,5,33 Biased stereotypes for individuals with SCAs 35 can influence expectations and subsequent reporting for subjective measures.…”

“…In a 2018 study, health status was the most significant factor associated with QOL in men with 47,XXY, suggesting QOL may be increased if chronic health conditions are improved. In addition, many conditions contributing to morbidity in individuals with SCAs are preventable or at least treatable . We hypothesize that a more timely diagnosis could optimize medical care, thus leading to better QOL with aging.…”

“…Population registries of clinically ascertained men with SCAs in European countries report a decreased lifespan and higher incidence rates for nearly all clinical diagnostic codes compared with sex- and age-matched controls . A 2022 study using the UK Biobank identified 356 men via genotype array to have X or Y chromosome polysomy .…”