Diagnosis and treatment of familial male precocious puberty caused by LHCGR gene mutation: two case reports and literature review

Abstract

Objective: To report the clinical features, gene detection results and treatment results of two patients with familial male limited precocious puberty(FMPP). Methods: Detailed medical history collection and physical examination were carried out in 2 FMPP patients. LHRH challenge test, sex hormone, adrenal cortical hormone and other tests and relevant imaging examinations were performed. At the same time, peripheral blood of related family members was collected for gene detection, and relevant literature was retrieved in the Chinese database and PubMed database for comprehensive discussion. Results: The initial diagnosis age of the two patients was 6 years and 1 month (case 1) and 3 years and 7 months (case 2), respectively. The symptoms were penis and testis enlargement, accelerated growth, and advanced bone age. Case 2 was accompanied by aggressive behavior. Laboratory examination indicated that the peak value of luteinizing hormone was 7.28 mIU/mL and 4.96 mIU/mL respectively, and the basal testosterone level rose to 2.49 ng/mL and 3.58 ng/mL, while no abnormality was found in imaging examination. According to the medical history and various examination results of 2 patients, central precocious puberty was clinically diagnosed. Gene testing showed that there were heterozygous variations in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene boys including c.1756TCTdel (p.Ser586del) variation and c.1723A>C (p.Ile575Leu) variation were identified in case 1 and case 2). It revealed that genetic variation in case 1 resulted from his father, while in case 2 came from his mother. According to the guidelines of The American College of Medical Genetics and Genomics(ACMG), genovariation of LHCGR gene was assessed as possible pathogenic variation, so it was clear that central precocious puberty was caused by LHCGR gene mutation. Conclusions: Two male FMPP caused by LHCGR genetic variation are reported in this paper, and c.1756TCTdel(p.Ser586del) in case 1 which is first reported both in demastic and aboard. For boys with central precocious onseting in low age or with poor treatment effect, test on LHCGR genetic variation may be performed.

Keywords

• |familial male precocious puberty|luteinizing hormone/choriogonadotropin receptor gene|functional acquired mutation|etiology diagnosis