The aim of this study was to review the growth data, gonadal function and tumour risk of children and adolescents with 45,X/46,XY mosaicism who presented to a single centre in China. We conducted a retrospective review of the records of 32 patients with 45,X/46,XY mosaicism or variants who were hospitalized from August 2005 to September 2018. The main outcomes measured were growth data, genital phenotype, gonadal function, gonadal position, and histological results. A total of 32 patients were included. The age at diagnosis ranged from 0.6 to 16.3 years. Nineteen patients exhibited ambiguous genitalia, 12 had short stature, and 1 showed a lack of breast development. Seventeen patients were raised as males, and 15 were raised as females. The external masculinisation score (EMS) of patients raised as male was 4.5 (1~12) [median (range)]. The EMS of the females was 0 (0~1.5) [median (range)]. Patients showed normal heights under 2 years old, with a height SDS of 0 (− 1.5~1.4) [median (range)]. Growth appeared to decelerate after age 2 years, with SDS decreased to − 2.8 (− 3.0~ − 0.9) [median (range)]. The percentage of short stature was higher in females than in males (76.9% vs 50.0%). Twenty-five patients had gonadal pathological results. Complete gonadal dysgenesis (CGD) and mixed gonadal dysgenesis (MGD) were the most common pathogenic subtypes, accounting for 48.0 and 36.0%, respectively. Ovotesticular tissue was observed in only 4.0% of patients. Gonadoblastoma and positive OCT3/4 results were found in 18.8% of gonads in children over 2 years of age. Palpable gonads accounted for 50% of these. All patients who had gonadoblastoma were raised as females. Patients with 45,X/46,XY might have normal heights until 2 years old. Growth decelerations after 2 years of age were common. Patients who are being raised as females seemed to be shorter than males. CGD and MGD were the most common gonadal pathogenic subtypes. The tumour risk is high in these patients, even in palpable gonads and female patients.

Context The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. Objective This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. Design A prospective, observational, posttrial study (NCT03290235). Setting, participants and intervention Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. Main outcomes measures Height SD score (Ht SDS) at 12, 24, and 36 months. Results A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. Conclusions PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

KBG syndrome (KBGS) is a rare autosomal dominant inherited disease that involves multiple systems and is associated with variations in the ankyrin repeat domain 11 (ANKRD11) gene. We report the clinical and genetic data for 13 Chinese KBGS patients diagnosed by genetic testing and retrospectively analyse the genotypes and phenotypes of previously reported KBGS patients. The 13 patients in this study had heterozygous variations in the ANKRD11 gene, including seven frameshift variations, three nonsense variations, and three missense variations. They carried 11 variation sites, of which eight were previously unreported. The clinical phenotype analysis of these 13 patients and 240 previously reported patients showed that the occurrence rates of craniofacial anomalies, dental anomalies, global developmental delays, intellectual disability/learning difficulties, limb anomalies, and behavioural anomalies were >70%. The occurrence rates of short stature, delayed bone age, and spinal vertebral body anomalies were >50%. The frequency of global developmental delays and intellectual disability/learning difficulties in patients with truncated ANKRD11 gene variation was higher than that in patients with missense variation in the ANKRD11 gene (p < 0.05). Collectively, this study reported the genotypic and phenotypic characteristics of the largest sample of KBGS patients from China and discovered eight new ANKRD11 gene variations, which enriched the variation spectrum of the ANKRD11 gene. Variation in the ANKRD11 gene mainly caused craniofacial anomalies, growth and developmental anomalies, skeletal system anomalies, and nervous system anomalies. Truncated variation in the ANKRD11 gene is more likely to lead to global growth retardation and intellectual disability/learning difficulties than missense variation in ANKRD11.

S: Background and objective: The study was performed to determine whether catch-up growth is associated with the development of insulin resistance and to explore serum endocrine markers associated with the metabolism of adipose tissue in a Chinese population born small for gestational age(SGA) Subjects and methods: We recruited 56 children born SGA with catch-up growth and 55 born without catch-up growth, who were further grouped into groups I (with BMI catch-up) and II (without BMI catch-up) respectively, as well as 52 children born appropriate for gestational age (AGA) with normal height. Their serum fasting insulin, fasting glucose, insulin-like growth factor-1, adiponectin, IGFBP-1, triglyceride concentrations, and the homeostasis assessment model for insulin resistance (HOMA-IR) were evaluated. Results: (1) The HOMA-IR values in SGA-I with catch-up growth group were significantly higher than those in SGA-II with catch-up growth, SGA-I without catch-up growth and AGA children respectively. (2) The serum adiponectin levels of individuals in the SGA-I without catch-up growth and SGA-II with catch-up growth groups were significantly lower than those from the SGA-II without catch-up growth group. There was no difference in triglyceride or IGFBP-1 levels among the groups. (3) The degree of HOMA-IR was positively correlated with age, current BMI and △height SDS in SGA children. Conclusion: The development of insulin resistance and lower levels of adiponectin were closely correlated with higher BMI and the postnatal height catch-up growth in SGA children.

Context and Objective This case control study was designed to investigate the association between mutation of 10 single nucleotide polymorphism (SNP) loci (rs1132506, rs5780218, rs192636495, rs4889, rs184749, rs12985070, rs708910, rs932491, rs8074995, and rs2306877) in all 5 genes (KISS1, GPR54, PLCB1, PRKCA, and ITPR1) in the kisspeptin/GPR54 pathway and the risk of early puberty in Chinese Han girls. Design and Participants A total of 314 pairs of early puberty girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of each SNP were determined and the effect of loci variation on early puberty was investigated. Results rs5780218 was significantly associated with early puberty in additive, dominant, and recessive models of inheritance after adjusting for confounding factors (P_r < .05). After stratification, rs5780218 variation (odds ratio [OR], 1.650, 95% confidence interval [CI], 1.155-2.355 in additive models and OR, 2.116; 95% CI, 1.187-3.770 in recessive models) increased the risk of central precocious puberty (CPP); mutation in rs708910 (OR, 2.768; 95% CI, 1.305-5.872 in recessive model) had a positive association with the risk of CPP; and rs932491 variation was negatively associated with early and fast puberty (EFP) (OR, 0.309; 95% CI, 0.144-0.661 in additive models and OR, 0.317; 95% CI, 0.141-0.713 in dominant models). Conclusions Our study suggests that mutation in rs5780218 and rs708910 increases the risk of CPP. rs932491 variation may have a protective effect on the risk of EFP. Further studies in larger populations or with people from different regions are needed to verify our findings.

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4–8 years with IPT. Methods: IPT girls confirmed by GnRH stimulation test aged 4–8 years hospitalized from January 2015 to April 2018 at Shenzhen Children’s Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. Results: Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p < 0.001). Serum IGF-1 SDS (OR = 1.926, p<0.001), BMI SDS (OR = 1.427, p = 0.001) and DHEAS SDS (OR = 1.131, p = 0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n = 237), overweight (19.15%, n = 81) and obesity (24.82%, n = 105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ² = 18.088, p<0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p = 0.009) and DHEAS SDS (p = 0.003) affected BA advancement independent of BMI SDS. Conclusions: Girls with IPT confirmed by GnRH stimulation test aged 4–8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.