Association between domains of quality of life and patients with Klinefelter syndrome: a systematic review

Abstract

Klinefelter syndrome (KS) is the second-most prevalent chromosomal disorder in men, though late diagnosis is very common and 50-75% of men remain undiagnosed. Evidence suggests that men with KS have impaired Quality of Life (QoL) but research on how the diagnosis of KS is associated with different QoL domains and what factors influence patients’ QoL is limited. This study aimed to provide a systematic review of the published evidence on factors that influence QoL in men with KS. DESIGN: Systematic review and meta-analysis with narrative synthesis. METHODS: Medline, Cochrane, Embase, Psychinfo, CINAHL, BASE and relevant publication reference lists were searched in January 2021. Eligible studies included RCTs, cohort studies, cross-sectional studies and epidemiology studies on KS and its effect on QoL and all domains of WHOQOL-100. Clinical studies with no date restriction published in English were included. RESULTS: Thematic analysis was completed on thirteen studies, with a meta-analysis of intelligence quotient (IQ) completed on seven studies. Twelve out of 13 studies suggested that KS negatively affected QoL outcomes and KS was associated with impairments in physical, psychological, level independence and social relationship domains of WHOQOL-100. Meta-analysis suggested men with KS have significantly lower full-scale Intelligence Quotient versus controls (P <0.00001). CONCLUSIONS: This is the first evidence synthesis of QoL in men with KS. Current evidence suggests that combined physical and psychological impairments affect men with KS who also experience impairments in relationships and independence in society. Further research is needed to identify factors that influence QoL in men with KS.

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 . 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 , 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 perhaps because MVP does not capture deaths prior to enrollment; thus far, follow-up is relatively short, and the life expectancy of our controls was young (approximately 70 years), possibly reflecting worse health among US veterans. 34 …”

“…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 . In contrast, we did not find greater mortality, perhaps because MVP does not capture deaths prior to enrollment; thus far, follow-up is relatively short, and the life expectancy of our controls was young (approximately 70 years), possibly reflecting worse health among US veterans …”

“…Most of the findings in the study by Zhao et al aligned with prior data, including an 85% nondiagnosis rate and worse overall health outcomes compared with men with 46,XY from both self-report and medical record data sources. In addition to increased morbidity and mortality outcomes, a meta-analysis summarizing the published literature on QOL in men with 47,XXY found a negative association with physical, psychological, and social QOL domains . However, on the individual level, the phenotypic result of an additional sex chromosome is variable, and the net impact of a clinical diagnosis remains uncertain.…”

“…In addition to increased morbidity and mortality outcomes, a meta-analysis summarizing the published literature on QOL in men with 47,XXY found a negative association with physical, psychological, and social QOL domains. 8 However, on the individual level, the phenotypic result of an additional sex chromosome is variable, and the net impact of a clinical diagnosis remains uncertain.…”