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

https://doi.org/10.1016/j.jpeds.2007.10.019Get rights and content

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.

Section snippets

Subjects

Subjects were generally referred to the pediatric endocrine clinic at Thomas Jefferson University. All subjects had postnatal karyotypes confirming the diagnosis of KS. The study was approved by the Human Studies Committee at Thomas Jefferson University and UT Southwestern Medical School. Informed consent/assent was obtained in all cases. The clinical evaluation was performed at Thomas Jefferson University, and the genetic evaluation was performed at UT Southwestern Medical School.

Anthropometric measurements

The clinical

Demographics

Our cohort included 55 boys, aged 2.0 to 14.6 years. The karyotype results included 51 boys; 47,XXY, 2 mosaic; 46,XY/47,XXY, and 2; 48,XXYY. The sample included 49 Caucasian boys, 5 African-American boys, and 1 Asian boy. 40 boys had received the diagnosis before the age of 2 years (35 for prenatal screening, 2 for hypotonia, 1 for developmental delay, and 2 for language delay). In the 35 boys in whom KS was diagnosed prenatally, 1 amniocentesis was performed for elevated alpha-fetoprotein

Discussion

This study describes the physical phenotype and hormonal and genetic findings in 55 boys with KS, aged 2 to14 years. We compared the phenotype of boys in whom the diagnosis was made prenatally through routine antenatal screening with that of boys in whom the diagnosis was made after birth, and we found no significant differences. Tall stature was observed at all ages within our cohort. Weight and BMI, on average, were also increased. There was a high prevalence of reduced penile length and

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    Supported by grants from the National Institutes of Health (RO1NS #050597, NS050597) and Institut de Recherche Endocrinienne et Metabolique (Paris, France).

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