Genital Anomalies in Klinefelter’s Syndrome

Abstract

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.

Cytogenetic abnormalities detected in patients with non-obstructive azoospermia and severe oligozoospermia

“…KS is the most common abnormality of sexual differentiation, and occurs in approximately 1 in 500 live births. KS is a form of primary testicular failure with testicular hypotrophy and elevated gonadotropin plasma levels, and it represents the most common form of male hypogonadism [27]. Ferlin et al reported that the prevalence of KS among infertile men is very high, up to 5% in severe oligozoospermia and 10% in azoospermia [28].…”

Cytogenetic abnormalities in 179 cases with male infertility in Western Region of Turkey: Report and review

“…KS is the most common abnormality of sexual differentiation, and occurs in approximately 1 in 500 live births. KS is a form of primary testicular failure with testicular hypotrophy and elevated gonadotropin plasma levels, and it represents the most common form of male hypogonadism [21]. Ferlin et al reported that the prevalence of KS among infertile men is very high, up to 5% in severe oligozoospermia and 10% in azoospermia [22].…”

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

“…5 There are few reported cases and they vary from penile chordee, hypospadias, and penoscrotal transposition. We reviewed the literature for patients diagnosed with Klinefelter syndrome before puberty with penoscrotal malformations; we searched PubMed using key words: Klinefelter syndrome, hypospadias, prepubertal age, chordee, bifid scrotum, and scrotal transposition (Table 1).…”

“…[6][7][8] In addition, 3 cases were excluded from a report due to the presence of ovary, ovotestes or atypical Karyotype. 5 Finally, we collected 15 patients, including our current case.…”