Genital anomalies in Klinefelter's syndrome

Background/aims: Klinefelter's syndrome is characterized by progressive testicular failure causing aspermatogenesis and androgen deficiency. Klinefelter patients classically have complete male sex differentiation, and genital anomalies are generally not recognized as associated features of the syndrome.

Methods: We reviewed the cases of Klinefelter's syndrome with genitalia abnormalities from the Cambridge Disorders of Sex Development Database, and also reviewed previous case reports of genital anomalies associated with Klinefelter's syndrome and its variants.

Results: We present seven Klinefelter patients with abnormalities of the genitalia, ranging from mild anomalies (chordee) to moderate undervirilisation (bifid scrotum and perineal hypospadias). Two cases were true hermaphrodites with karyotypes 47,XXY and 47,XXY/46,XX respectively. Though androgen insensitivity has been postulated previously as a possible pathogenic mechanism, we demonstrated normal androgen binding in 3 cases in which this was studied. Review of other case reports revealed a range of mild-to-severe abnormalities as well as cases reported as sex reversal, testicular feminization, and true hermaphroditism.

Conclusion: Genital anomalies are not commonly observed in Klinefelter's syndrome. However, it is important to acknowledge the association, and recognize Klinefelter's syndrome as one of the causes of abnormal genitalia at birth.