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Clinical and genetic features of 64 young male paediatric patients with congenital hypogonadotropic hypogonadism
Author(s) -
Wang Yi,
Gong Chunxiu,
Qin Miao,
Liu Ying,
Tian Yuanyuan
Publication year - 2017
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13451
Subject(s) - micropenis , kallmann syndrome , hypospadias , hypogonadotropic hypogonadism , medicine , delayed puberty , endocrinology , hypergonadotropic hypogonadism , testosterone (patch) , pediatrics , gynecology , hormone , surgery , disease , covid-19 , infectious disease (medical specialty)
Summary Context The 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 . Design The clinical and genetic features of patients with CHH were analysed, and the relationships between hypospadias, dual defects and genetics were investigated. Patients Patients who visited Beijing Children's Hospital and were positively diagnosed with CHH . Measurements The 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. Results Sixty‐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 PROKR 2 (17.6%), FGFR 1 (13.7%) and CHD 7 (7.8%). The frequency of PROKR 2 mutations was higher in dual HH when compared to other HH cases (6/15 vs 3/36, P = .021). Conclusions Micropenis 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 PROKR 2 mutations need to be evaluated to identify presumed dual defects.