PRIMARY OVARIAN INSUFFICIENCY IN TWO GIRLS WITH RETT SYNDROME

Objectives: Rett syndrome (RTT) is a progressive neurodevelopmental disorder, prevalent in female. Mutation of Methyl-CpG-binding protein 2 (MeCP2) gene, localized in the long arm of chromosome X (Xq28), is implicated in about 95% of classic RTT. There are no studies available about gonadal function in these patients. Methods: We report the cases of two girls with RTT (de novo mutation of MeCP2) who came to our attention for secondary amenorrhea at the age of 19 (patient 1) e 11.6 (patient 2) years of age. Both presented spontaneous pubertal development with menarche at the age of 11 and 10.3, respectively. Furthermore, they were both obese (BMI +2.4DS) and clinical hyperandrogenemia was reported in patient 1. Results: We first hypothesized as diagnosis menstrual irregularities in obese subjects, therefore we evaluated the hypothalamus-hypophysis-gonads axis functionality. Basal gonadotropin resulted slightly upper than normal values, estradiol was lower than normal range, adrenal steroids, prolactin, thyroid function e serology for coeliac disease resulted normal. Karyotype was normal (46,XX) in both. Pelvic ultrasound was normal for age in both patients. LHRH test highlighted a pronounced increase of FSH and of LH values in particular (LH peaks 169.95 mUI/ml in patient 1 and 84.36 mUI/ml in patient 2). Conclusions: Based on clinical and laboratory observations we diagnosed hypergonadotropic hypogonadism in both patients. Moreover, we supposed in these patients a primary ovarian insufficiency (POI). FMR1 (fragile X mental retardation 1) and FMR2 genes, often involved in POI with genetic origin, are localized in the long arm of chromosome X (Xq27.3 and Xq28, respectively) near to MeCP2 gene, and their mutations might determine POI in RTT patients. For this reason, we carried out a genetic survey to search FMR1 premutation and/or FMR2 deletions. Meanwhile our patients started a diet and patient 1 also started an estro-progestinic therapy.