[Association of the extra-gonadal manifestations with different pathogenic gene mutations in male patients with congenital hypogonadotropic hypogonadism].

OBJECTIVE: To explore the relationships between pathogenic gene mutations and extra-gonadal manifestations in male patients with congenital hypogonadotropic hypogonadism (CHH).

METHODS: A total of 15 genes were screened in 259 CHH patients by massively parallel DNA sequencing. The identified pathogenic mutations were confirmed by Sanger polymerase chain reaction (PCR). The extra-gonadal features in all patients were recorded.

RESULTS: Gene mutations were detected in 83 (32.0%) patients, which included FGFR1 (n=20), PROKR2 (n=19), CHD7 (n=16), KAL1 (n=14) and other genes (n=14), such as PROK2, FGF8, GNRHR, KISS1R, NELF and WDR11. Patients with KAL1 mutation displayed CHH related family history (n=5) and obesity (n=3). Patients with FGFR1 mutation presented with short stature (n=3), testicular hydrocele (n=2), lip-palate cleft (n=2) and dental dysplasia (n=1). Patients without detectable mutations may also exhibit obesity, mental retardation and short stature.

CONCLUSIONS: CHH patients may present with extra-gonadal manifestations, including anosmia, obesity, dental dysplasia, short stature and mental retardation. An obscure relationships could be found between the clinical features and different gene mutations, but it is difficult to speculate the types of pathogenic gene mutations according to these extra-gonadal manifestations.