45,X/46,XY mosaicism: phenotypic characteristics, growth, and reproductive function--a retrospective longitudinal study.

CONTEXT: Most previous studies of 45,X/46,XY mosaicism are case reports or have described single aspects of the disease. OBJECTIVE: The objective was to provide longitudinal data of patients with 45,X/46,XY mosaicism. DESIGN: This was a retrospective, longitudinal study conducted from June 1990 to January 2012. SETTING: The study took place at a tertiary pediatric and andrological referral center. PATIENTS OR OTHER PARTICIPANTS: Twenty-five patients (18 boys, seven girls) with 45,X/46,XY mosaicism and its variants were included and were compared to healthy controls. INTERVENTION(S): No interventions were included in the study. MAIN OUTCOME MEASURE(S): Phenotypes were scored using external masculinization scores. Serum LH, FSH, testosterone, estradiol, and inhibin B levels were reported in male patients. IGF-I levels and height were reported in all patients. Available biopsies/gonadectomies were histologically examined. RESULTS: Fourteen of 18 males had external masculinization scores consistent with normal virilization. Ten of 11 male patients experienced spontaneous puberty. Median height sd score was -2.0 (range, -3 to 0.3) for males and -2.2 (range, -2.5 to -1.4) for females, both considerably below genetic potential. Median 1-yr height gain after GH treatment in seven patients was 0.5 sd (0.1 to 1.2). All tissue samples from 15 patients (eight males, seven females) revealed abnormal gonadal histology. Four patients had carcinoma in situ (CIS); two had tissue samples available from early childhood, one showing CIS. CONCLUSIONS: Gonadal function in most 45,X/46,XY males, even those with genital ambiguity, seems sufficient for spontaneous puberty. Short stature and 45,X/46,XY mosaicism seem associated, but patients appear to benefit from GH treatment. Histology from two patients with biopsies from early childhood indicates that CIS originates before puberty.