ESPE Abstracts (2023) 97 P1-341

ESPE2023 Poster Category 1 Pituitary, Neuroendocrinology and Puberty (73 abstracts)

Correlation Analysis of Genotypes and Phenotypes of 91 young male paediatric patients with congenital hypogonadotropic hypogonadism

Dongxia Fu , Jiajia Chen & Haiyan Wei

Children’s Hospital Affiliated to Zhengzhou University Henan Children’s Hospital Zhengzhou Children’s Hospital, zhengzhou, China

Background: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH can be divided into Kallmann syndrome (KS) with dysosmia and normosmic Congenital hypogonadotropic hypogonadism (nCHH) according to the presence or absence of an olfactory disorder.

Methods: We retrospectively evaluated 91 CHH patients (56 KS and 35 nCHH) aged 0 to 18 years who were diagnosed at the Department of Endocrinology of the Children's Hospital Affiliated to Zhengzhou University from 2016 to 2021. We analysed the patients’ clinical data, including their hormone levels and gene sequences.

Results: In total, 81.3% of the patients had micropenis, including micropenis(24,26.4%), micropenis with cryptorchidism(38,41.8%), micropenis with hypospadias(9,9.9%), micropenis with hypospadias and cryptorchidism(3,3.3%); cryptorchidism(3,3.3%), and puberty absence(14,15.4%). A total of 51 patients with KS completed an MRI examination of the olfactory bulb. and 3.9% (2/51) reported hyposmia, However, no abnormal olfactory bulb, olfactory tract, or olfactory sulcus was found on the MRI. Olfactory bulb MRI showed 47(92.2%) cases of olfactory bulb dysplasia,33 (64.7%) cases of olfactory bundle were not clearly displayed.A total of 68 patients(KS=46, nCHH=22) underwent genetic testing,73.5% of cases(50/68) were found 19 CHH-related pathogenic genes. digenic mutations in 7.4% of cases (5/68), and trigenic mutations in 4.4% of cases (3/68). The most common mutations were PROKR2(10/68,14.7%), FGFR1(10/68,14.7%), CHD7(9/68,13.2%), ANOS1(5/68,7.4%). The most common mutations no signifificant difference in the proportion between KS and nCHH (all P>0.05). Comparing several common genes in CHH, it was found that patients with PROKR2 mutation had a higher proportion of normal testicular function, while patients with TCF12 mutation had relatively poor testicular function.

Conclusion: The diagnosis of CHH should be considered in patients with undescended testis of micropenis. Molecular genetics is an important means to diagnose CHH in children. Abnormalities of ANOS1, PROKR2, PROK2, FGFR1, and CHD7 genes lead to CHH with or without non-reproductive manifestations. Oligogenetic inheritance accounts for 11.8% of all CHH, which may be due to autosomal recessive inheritance or incomplete gene extransion. Except for anosmia, there was no significant difference in clinical phenotype between KS and nCHH. These findings provide greater insight into the diagnosis of CHH and will contribute to its clinical evaluation.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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