Genital anomalies in Klinefelter's syndrome.
OBJECTIVE
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.


CONCLUSIONS
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.
Lee
Yung Seng
YS
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Cheng
Anna Wai Fun
AW
Ahmed
Syed Faisal
SF
Shaw
Nick J
NJ
Hughes
Ieuan A
IA
D005837:Genitalia, Male / Q000002:abnormalities*; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D007713:Klinefelter Syndrome / Q000473:pathology*; D008297:Male; D050090:Ovotesticular Disorders of Sex Development / Q000473:pathology