Early Androgen Deficiency in Infants and Young Boys with 47,XXY Klinefelter Syndrome

Abstract

Background/Aims: Klinefelter syndrome (KS) is characterized by the karyotype 47,XXY. In this study, we evaluated the physical and testicular failure phenotypes of infants and young boys with KS. Methods: The evaluation included auxologic measurements, biologic indices of testicular function, and clinical assessment of muscle tone in 22 infants and young boys with KS, ages 1–23 months. Results: Mean length, weight, and head circumference in SDS were generally within the normal range at –0.3 ± 1.0, –0.1 ± 1.4, and 0.0 ± 1.5, respectively. Mean penile length and testicular volume SDS were –0.9 ± 0.8 and –1.1 ± 0.8, indicating significantly reduced penile and testicular size. Mean testosterone levels for the boys ≤6 and >6–23 months were 128 ± 131 (4.4 ± 4.5 nmol/l) and 9.5 ± 7.2 ng/dl (0.3 ± 0.2 nmol/l), respectively. High-arched palate was observed in 6/17 boys and clinodactyly (5th finger) was observed in 15/16 boys. Hypotonia was evaluated clinically and was noted to be present in 12/17 boys. Conclusion: The physical phenotype in infants and young boys with KS (1–23 months old) includes normal auxologic measurements and early evidence of testicular failure. Muscle tone was decreased in most of the boys. Testicular volume and penile length were diminished, indicating early androgen deficiency. The neonatal surge in testosterone was attenuated in our KS population. Thus, infants and young boys with KS have evidence of early testicular failure. The etiology of this failure and the clinical role of early androgen replacement require further study.

Are Adolescent Boys with Klinefelter Syndrome Androgen Deficient? A Longitudinal Study of Finnish 47,XXY Boys

“…Thus, impaired T secretion is not an evident feature of KS boys during puberty. In fact, to our knowledge, only two studies on KS boys have demonstrated diminished T secretion before puberty (30,31), but these studies comprised infant KS boys, and the results cannot therefore be directly extrapolated to peripubertal and pubertal KS subjects.…”

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

“…Testicular volume is significantly reduced in infants and prepubertal boys with KS as compared with similarly aged healthy boys (15,16), indicating that the number of seminiferous tubules is significantly reduced before puberty.…”

“…The mini-puberty represents a window suitable for studying the function of the pituitary-gonadal axis at this young age by measuring the spontaneous, basal hormone levels (32). Although controversies exist as to whether the HPG axis is impaired in KS infants (16,33,34,35), the latest and largest study on the mini-puberty in KS demonstrated normal testosterone concentrations (35). Importantly, however, the testosterone concentrations were below the median of the controls, which may indicate a subtle Leydig cell dysfunction, although this was not supported by an elevation of LH concentrations (35).…”

Pre-pubertal diagnosis of Klinefelter syndrome due to peno-scrotal malformations; Case report and review of literature

“…17 Androgen deficiency can be a cause of psychosexual underdevelopment in these patients 18 and early prepubertal management with androgen can significantly improve their neurodevelopmental outcome. 17 Following the standard recommendations of karyotyping according to Chicago Conesus Conference on Disorders of Sexual Differentiations can help in early diagnosis and management of Klinefelter patients whom are often undiagnosed before puberty.…”