Effect of Ascertainment and Genetic Features on the Phenotype of Klinefelter Syndrome

ObjectiveTo describe the Klinefelter Syndrome(KS) phenotype during childhood in a large cohort.Study designClinical 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.ResultsMean 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.ConclusionsBoys 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.