Socio‐economic factors affect mortality in 47,XYY syndrome—A comparison with the background population and Klinefelter syndrome

Abstract

Mortality among males with 47,XYY is increased due to a host of conditions and diseases. Clinical studies have suggested a poorer educational level and social adaptation among 47,XYY persons. We wanted to study the socio-economic profile in 47,XYY persons and the impact on mortality. We conducted a register study using several Danish nationwide registries. 206 47,XYY men and 20,078 controls from the background population and 1,049 controls with Klinefelter syndrome were included. Information concerning marital status, fatherhood, education, income, and retirement were obtained. Compared to the background population, 47,XYY men had fewer partnerships, were less likely to become fathers, had lower income and educational level, and retired at an earlier age. The mortality among 47,XYY men was significantly increased with a hazard ratio (HR) of 3.6 (95% confidence interval: 2.6-5.1). Adjusting for marital and educational status reduced this HR to 2.7. Compared to Klinefelter syndrome, 47,XYY had significantly fewer partnerships, were more likely to become fathers, but had lower income. Mortality among 47,XYY men was increased compared with Klinefelter syndrome with a HR of 1.36. The results show a severely inferior outcome in all investigated socio-economic parameters compared to the background population and an affected profile compared with Klinefelter syndrome, even though the population in Denmark has equal and free access to health care and education. We conclude that 47,XYY is often associated with a poorer socio-economic profile, which partly explains the increased mortality.

Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study

“…Late diagnosis as well as non-diagnosis of SCAs have been a continuous concern [25–27, 38] since SCAs are associated with increased morbidity and mortality [3, 5, 20, 23, 39], learning and/or behavioral disabilities [40–45] as well as reduced socioeconomic outcomes. Although there is lack of evidence regarding the influence of age at diagnosis on long-term outcomes, we believe that early diagnosis will provide better overall long-term outcome in SCAs by providing an opportunity for timely intervention against associated health problems as well as against learning and behavioral problems.…”

A unique association of Noonan syndrome and 47,XYY syndrome in a male presenting with failure to thrive

“…47,XYY syndrome is also a relatively common genetic condition, occurring in males in ~1 per 1000 live births [ 5 ]. Many are diagnosed in adolescence or adulthood, as many who have this condition present only with tall stature.…”

“…In fact, it is believed that 85% or more of males with XYY are never diagnosed [ 2 ]. Tall stature in 47,XYY syndrome is thought to be due to triplicate expression of the short stature homeobox-containing gene ( SHOX ) located on the distal ends of Xp and Yp [ 5 ]. Other characteristics include autistic traits and neurocognitive changes, such as speech and language problems, and reduced motor skills and educational achievement [ 5 ].…”

“…Tall stature in 47,XYY syndrome is thought to be due to triplicate expression of the short stature homeobox-containing gene ( SHOX ) located on the distal ends of Xp and Yp [ 5 ]. Other characteristics include autistic traits and neurocognitive changes, such as speech and language problems, and reduced motor skills and educational achievement [ 5 ]. There is also increased risk of impulsivity, poor adaptation to social situations and behavioral problems related to externalizing behaviors [ 6 ].…”

Brain morphology in children with 47,XYY syndrome: a voxel‐ and surface‐based morphometric study

“…Finally, WM, GMV, SA and CT abnormalities observed in the posterior parietal cortex could negatively impact attention, sensorimotor processing and integration of visual and auditory constructs (Arnsten & Rubia ; Cohen et al ; Iacoboni ). Taken together, it is possible that the cognitive profile resulting from these brain alterations could contribute to the increased risk for a diagnosis of ASD (Ross et al ) and the relatively decreased socioeconomic outcome (Stochholm et al ) reported in the XYY population.…”