Background: Abnormalities in the hypothalamo-pituitary-gonadal axis have been reported in Noonan syndrome (NS) males but few data are available in female patients. Objective: The aim of this retrospective study was to evaluate the gonadal function of female patients with NS and to look for genotype-phenotype correlations. Patients and Methods: The study population included 19 girls/adolescents with a genetically confirmed diagnosis of NS and with available clinical (Tanner stages and age of first menstruations) and/or hormonal (serum gonadotropins, inhibin B, and anti- Müllerian hormone [AMH] levels) data on gonadal function. Results: Twelve (63.2%) girls had entered puberty and the age at pubertal onset and at menarche were 12.0 and 15.0 years respectively, corresponding to a delay of 1.5 to 2 years compared with the general healthy population. Except two SOS1-patients with AMH values above the upper limit of normal, all AMH values were in the normal range through childhood and adolescence. NS girls had similar levels of inhibin B, transformed to age- and gender-specific SDS using the published reference data, compared with the general population (mean SDS: 0.0; P = 0.94). Serum inhibin B levels SDS were significantly lower in NS with multiple lentigines (NSML)-PTPN11 patients compared with the general population and NS-PTPN11 patients (P = 0.01 for both); there was no other genotype-phenotype correlation. Conclusions: These data suggest that NS females display normal albeit delayed onset at puberty and normal ovarian function.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology