Phenotype and Adverse Quality of Life in Boys with Klinefelter Syndrome

To characterize associations among psychosocial well-being, physical phenotype, and sex hormones in a sample of youth with Klinefelter syndrome (KS). We hypothesized that KS physical traits (phenotype) are associated with adverse psychosocial health measures and that testosterone levels are associated with adverse psychosocial health.

Forty-three boys with KS (ages 8-18 years) participated in a cross-sectional study. Participants underwent physical examination, hormone analyses, and psychosocial health questionnaires.

Using an investigator-developed Klinefelter Phenotype Index Scale, the number of KS physical traits ranged from 1-13 (mean 5.1 ± 1.9). Pubertal boys presented with more KS traits compared with prepubertal boys (5.6 vs 4.2, P = .01). Boys diagnosed prenatally had a milder phenotype compared with those diagnosed postnatally. Gonadotropins were elevated without androgen deficiency in 45%. Psychosocial health scores indicated adverse quality of life (QOL) (67%), low self-esteem (38%), poor self-concept (26%), and risk for depression (16%) without a difference between pubertal groups. Linear regression showed that 22% of the variance in QOL (P = .0001) was explained by phenotype. Testosterone level was not associated with psychosocial health measures.

Depending on the degree of phenotypic abnormality, boys with KS may be at risk for impaired QOL. Testosterone levels were not shown to influence psychosocial health. The Klinefelter Phenotype Index Scale may be a useful tool to characterize KS features in boys.