Outcomes of Patients With Familial Central Precocious Puberty due to Mutations of MKRN3 Gene After Treatment With Gonadotropin-Releasing Hormone Agonist.

Objective: To assess the therapeutic effects of gonadotropin-releasing hormone agonist (GnRHa) on children with familial central precocious puberty (FCPP) due to Makorin ring finger Protein 3 (MKRN3) gene mutations. Methods: Children with central precocious puberty (CPP) who were admitted to the Pediatric Endocrinology Department of Shanghai Ruijin Hospital from 2014 to 2021 were enrolled, of whom 4 FCPP children with MKRN3 gene mutations, including 3 girls and 1 boy, were selected as research subjects. Their height, weight, body mass index (BMI), predicted adult height (PAH), bone age, bone age advance (BAA, bone age minus chronological age), height-based standard deviation scores (Ht-SDS) corresponding to the chronological age, concentrations of sex hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]), and development of sexual organs were compared before and after at least 2 years of GnRHa treatment. Results: After at least 2-year GnRHa treatment, mean volume of uterus of three girls decreased from 5.72 ± 2.58 to 2.12 ± 1.62 mL (p < 0.05) and mean volume of ovaries decreased from 3.61 ± 1.67 to 0.62 ± 0.22 mL (p < 0.05) as well, indicating that the gonadal development was effectively inhibited. Basal concentrations of LH and FSH in serum decreased, indicating that the secretion of gonadotropin in the anterior pituitary is inhibited. BAA and Ht-SDS decreased, suggesting that the bone age was restrained, and the growth rate was slowed down to some extent. Both average BMI and obesity prevalence (X 2 = 7.188, p=0.029) decreased during the treatment. No obvious adverse reaction was found. Conclusion: Long-term GnRHa treatment could effectively inhibit the gonadal development and FSH secretion in FCPP children with MKRN3 gene mutations, while this inhibitory effect on the bone age and growth rate was not obvious. Adverse reactions such as increased prevalence of obesity were not found. A large-scale, long-term follow-up study is required to indicate whether patients' final height (FH) could reach PAH or target height (TH).