ODP402 Adult height and reproductive outcome of Klinefelter men with a 46,XX/47,XXY mosaicism

Abstract

Abstract Background Mosaicism in Klinefelter Syndrome (KS) is reported in 15–20%, but 46,XX/47,XXY mosaicismis extremely rare and presents either during infancy with ambiguous genitalia or during adolescence with gynecomastia or microorchidism. In view of the scarce data on adult outcomes (1,2), we here comprehensively report the skeletal and reproductive health outcome in two individuals with 46,XX/47,XXY KS. Clinical cases The first case was born at 40 weeks after a spontaneous conception with a birth length of 49 cm. At birth right cryptorchidism, but a normally developed penis and scrotum was present. Surgical intervention at the age of 1 year, showed a right abdominal testicular nubbin. He was investigated at the age of 17 years for left microorchidism (6ml) contrasting with a normal genital development (Tanner G5). Hormonal investigation showed hypergonadotropinemia with a normal serum testosterone. Peripheral blood karyotype showed mosaicism 46,XX (60%)/47,XXY (40%). At the age of 18 years, standing height was 164.5 cm (mid-parental height (MPH) 173.5 cm). BMI was 19 kg/m2. Hormonal evaluation showed an unmeasurable serum inhibin B, elevated gonadotropins (LH 43 IU/L and FSH 65 IU/L), but a normal testosterone and estradiol. Ultrasound of the left testis showed a normal echo pattern. Azoospermia was documented. Lumbar spine bone mineral density (LS-BMD) was -1 SDS. The second case was born at 37 weeks after ICSI with a birth length of 49 cm. External genitalia at birth were normal. However, routine karyotyping after ICSI conception showed a mosaicism 46,XX (50)/ 47,XXY (50). A normal pubertal development apart from an arrest in testicular development at the age of 15 years was documented. At the age of 18 years, his height was 176.8 cm (MPH 184 cm), BMI 26 kg/m2, Tanner stage G5 and testes volumes 8/8 ml. Hormonal evaluation showed low inhibin B (43.4 ng/l), slightly elevated gonadotropins (LH 16.1 IU/L and FSH 12.5 IU/L), and normal testosterone and estradiol. Ultrasonography of the scrotum showed normal testicular structure. LS-BMD SDS was 1. Conclusion 46,XX/47,XXY KS men, who present with normal male genitals at birth, can have a normal pubertal progression with the exception of a mid-pubertal testicular regression, but in contrast to men with a 46,XY/ 47,XXY constitution, appear at risk for a shorter stature than expected for parental height. References Velissariou V et al., European Journal of Medical Genetics (2006) 49, 331-337Matsuki S, Journal of Urology (1999) 161 (5), 1573-74 Presentation: No date and time listed