Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome.

OBJECTIVE: To describe the Klinefelter Syndrome (KS) phenotype during childhood in a large cohort. STUDY DESIGN: Clinical assessment, measurement of hormonal indices of testicular function, and parent of origin of extra X chromosome were assessed in a cross-sectional study of 55 boys with KS, aged 2.0 to 14.6 years, at an outpatient center. RESULTS: Mean height and body mass index SD scores (SDS +/- SD) were 0.9 +/- 1.3 and 0.4 +/- 1.4, respectively. Mean penile length and testicular volume SDS were -0.5 +/- 0.9 and -0.9 +/- 1.4. Testosterone levels were in the lowest quartile of normal in 66% of the cohort. Other features included clinodactyly (74%), hypertelorism (69%), elbow dysplasia (36%), high-arched palate (37%), hypotonia (76%), and requirement for speech therapy (69%). Features were similar in boys in whom the diagnosis was made prenatally versus boys in whom the diagnosis was made postnatally. There was no evidence for a phenotypic effect of parent of origin of the extra X chromosome. CONCLUSIONS: Boys with KS commonly have reduced penile length and small testes in childhood. The phenotype in boys with KS does not differ according to ascertainment or origin of the extra X chromosome. Boys with KS may be identified before puberty by tall stature, relatively decreased penile length, clinodactyly, hypotonia, and requirement for speech therapy.