ContextThe diagnosis of congenital hypogonadotropic hypogonadism (CHH) in prepuberty has always been challenging. Here, we aimed at studying the clinical and genetic features of paediatric CHH, especially the phenotype of hypospadias and dual defects (patients showing hypothalamic and/or pituitary defects and testicular hypoplasia), so as to have a better understanding of CHH. DesignThe clinical and genetic features of patients with CHH were analysed, and the relationships between hypospadias, dual defects and genetics were investigated. PatientsPatients who visited Beijing Children's Hospital and were positively diagnosed with CHH. MeasurementsThe collected data included sex hormones, MRI of the olfactory bulb, human chorionic gonadotrophin (hCG) test and genetic testing. We analysed clinical features and genetic results, especially hypospadias and dual defects, and compared the stimulated testosterone (T) levels in patients with and without cryptorchidism. ResultsSixty-four patients were positively diagnosed, and forty-seven (73.4%) had Kallmann syndrome (KS). Four patients (6.3%) had hypospadias, including 2 KS. Micropenis combined with cryptorchidism was the most common phenotype (39%). Approximately two-third of patients showed a poor response to hCG; 15 cases were diagnosed with dual defects, and there were no significant differences between those with and without cryptorchidism. Twenty-six cases (51%) of 51 patients were identified as having classical HH mutations, affecting 10 different genes, with oligogenic mutations in 5 cases (9.8%). The most common mutations were in PROKR2 (17.6%), FGFR1 (13.7%) and CHD7 (7.8%). The frequency of PROKR2 mutations was higher in dual HH when compared to other HH cases (6/15 vs 3/36, P=.021). ConclusionsMicropenis and/or cryptorchidism can serve as important signs for the diagnosis of HH in paediatrics, and the coexistence of hypospadias does not exclude the diagnosis of CHH, including KS or normosmic isolated HH (nHH). Testicular function may be impaired earlier than expected, and PROKR2 mutations need to be evaluated to identify presumed dual defects.
基金：
National Key Research and Development Program of China [2016YFC0901505]; Beijing Municipal Science and Technology Funding [Z151100003915103]
第一作者机构：[1]Capital Med Univ, Natl Ctr Childrens Hlth, Beijing, Peoples R China;[2]Capital Med Univ, Beijing Childrens Hosp, Dept Endocrinol Genet Metab & Adolescent Med, Beijing, Peoples R China;[3]Capital Med Univ, Beijing Childrens Hosp, Beijing Key Lab Genet Birth Defects, Beijing, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Natl Ctr Childrens Hlth, Beijing, Peoples R China;[2]Capital Med Univ, Beijing Childrens Hosp, Dept Endocrinol Genet Metab & Adolescent Med, Beijing, Peoples R China;[3]Capital Med Univ, Beijing Childrens Hosp, Beijing Key Lab Genet Birth Defects, Beijing, Peoples R China;
推荐引用方式(GB/T 7714)：
Wang Yi,Gong Chunxiu,Qin Miao,et al.Clinical and genetic features of 64 young male paediatric patients with congenital hypogonadotropic hypogonadism[J].CLINICAL ENDOCRINOLOGY.2017,87(6):757-766.doi:10.1111/cen.13451.
APA：
Wang, Yi,Gong, Chunxiu,Qin, Miao,Liu, Ying&Tian, Yuanyuan.(2017).Clinical and genetic features of 64 young male paediatric patients with congenital hypogonadotropic hypogonadism.CLINICAL ENDOCRINOLOGY,87,(6)
MLA：
Wang, Yi,et al."Clinical and genetic features of 64 young male paediatric patients with congenital hypogonadotropic hypogonadism".CLINICAL ENDOCRINOLOGY 87..6(2017):757-766
