This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Disorders of sex development (DSD) are characterized by atypical development of chromosomal, gonadal, or phenotypic sex. 45X,46XY mosaicism is a type of sex chromosome DSD which presents with a wide heterogeneity of manifestations. We report the case of a 13-year-old phenotypically female who presented with clitoromegaly at puberty. Testosterone level was elevated on serology. Out of the 50 cells examined, 43 cells had Monosomy X while 7 cells had a normal male karyotype. She was managed by a multidisciplinary team. Due to the presence of Y chromosome, the solid nodular structure seen on the right gonad in magnetic resonance imaging and the pain caused by the phallus, Laparoscopic bilateral gonadectomy, salpingectomy and clitoroplasty were done after a shared decision making. Histopathology revealed Gonadoblastoma and Germ cell neoplasia-in-situ of the right gonad justifying timely removal. She was then maintained on estrogen for induction of secondary sexual characteristics.

With the increasing rate of overweight and obesity in children worldwide, adiposity rebound(AR)closely related to obesity has become the spotlight, and early AR phase has a broad impact on pubertal development in girls, but the specific mechanism of action isn't very clear.This paper is review of the prevalence of early AR at home and abroad, and its influencing factors, the impact of AR on the adolescent development of girls and related mechanisms, to identify high-risk individuals with early AR, early AR to identify early adolescent development, and take early intervention measures to promote children's health.
Female ; Adolescent ; Child ; Humans ; Adiposity ; Pediatric Obesity/epidemiology* ; Adolescent Development ; Body Mass Index ; Overweight/epidemiology*

OBJECTIVE: To explore the genetic basis for a rare case with Disorder of sex development. METHODS: Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out. RESULTS: The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223). CONCLUSION The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
Female ; Humans ; Adolescent ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Y Chromosome ; Sexual Development ; Mosaicism

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective: To examine increases in average height among Chinese children and adolescents. Methods: The data were obtained from the China Health and Nutrition Survey conducted during the period 1989-2015. A stratified multistage cluster sampling method was utilized to select participants aged 2-22 years in each province. Linear regression was used to examine the effects of age, birth cohort, and survey period on height. Results: A total of 15,227 males and 13,737 females were included in the final analysis. Age (A) showed a continuous effect on height. The average heights of the investigated groups increased continuously during the investigation period. By 2015, the average height of the overall group increased by 7.87 cm compared to the average height during the 1989 survey. Moreover, birth year (cohort, C) also had a stable effect on height. Using the height of individuals born in or before 1975 as a reference, the average height of each birth cohort increased in comparison to the previous birth cohort. Conclusions The height of Chinese children and adolescents was affected by age, period, and cohort effects, and this effect is governed by certain rules. The age-period-cohort model can be used to analyze the trends of children's and adolescent's heights. The findings provide a scientific basis for the formulation of children's and adolescents' growth and development policies in China.
Adolescent ; Adolescent Development ; Adolescent Health ; Age Factors ; Body Height ; Child ; Child Development ; Child Health ; Child, Preschool ; China ; Female ; Health Status Indicators ; Health Surveys ; Humans ; Linear Models ; Male ; Sex Factors ; Young Adult

The main purpose of the National Nutrition and Health Systematic Survey for children 0-17 years of age in China (CNHSC) was to collect basic data on the nutrition, development, and health status for children in different regions across China using evidence-based, reliable, and cost-effective approaches. Children and their parents or guardians from seven regions (south, southwest, north, northwest, eastern, central, and northeast China) in China were recruited. A multi-stage stratified randomized sampling method was used. Two provinces were randomly sampled from each of the seven regions, from which one urban district and one rural country were also randomly sampled, resulting in a total of 28 survey counties/districts. Dietary surveys, health examinations, laboratory testing, and questionnaires were used to collect dietary intake, nutritional status, child development, and health status information. Nutrition, health, and lifestyle assessment of children and their parents was determined using the Knowledge Attitude Practice (KAP) survey. Greater than 100,000 children (38,000 children < 6 years of age and 66,000 children 6-17 years of age) completed the survey. The survey provided comprehensive data on child nutrition and health status for future studies and will serve as the basis for an integrated nutrition and health improvement strategies proposal for children in China.
Adolescent ; Child ; Child Development ; Child, Preschool ; China ; Health Status ; Health Surveys ; Humans ; Infant ; Infant, Newborn ; Nutrition Surveys

BACKGROUND: The incidence of melanoma increased rapidly throughout the last decades, with overexposure to ultraviolet (UV) radiation being an established risk factor. Due to their intensive sun exposure, many student athletes (SAs) have an increased risk for skin cancer. The Clever in Sun and Shade Program (CSSP) aims at enforcing positive attitudes toward UV protection (UVP) and at supporting sports schools in establishing UVP strategies. METHODS: CSSP was developed in 2019 using participatory program planning (PPP) as well as following WHO recommendations for UVP at schools. After drafting first material, within a PPP groups were conducted at a partner school (convenience sample 1) with students (n = 20), teachers (n = 5), school administration (n = 2), and coaches (n = 5). Materials were then adapted. Program acceptance and feasibility were tested at two further schools (convenience sample 2) with PPP groups of students (n = 95) and school administration (n = 2). Content analyses and descriptive statistics were conducted. RESULTS: Less than 50% of SAs and coaches of sample 1 expressed positive attitudes toward UVP, less than 10% reported appropriate UVP behavior. By using PPP, program material was adapted to the target groups' needs, i.e., by including specific barriers and solutions. Only the most accepted video drafts were produced. The majority of SAs of sample 2 (80-86%) used predominantly positive adjectives such as "important" and "positive" to describe the completed videos and the behavior self-check poster. CONCLUSIONS PPP process has greatly influenced concept and materials of CSSP for sports schools. Integration of future program participants has proven to be an important component in creating a fitting and feasible program. CSSP for sports schools is a program free of charge that enables sports schools to integrate UVP into their daily routine. It will be disseminated in cooperation with German Olympic Sports Confederation and German Cancer Aid in 2021.
Adolescent ; Athletes ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Melanoma ; prevention & control ; Program Development ; Schools ; Skin Neoplasms ; prevention & control ; Sports ; Ultraviolet Rays

To evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). Seventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. HV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( =2.78 and 2.20, all < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( >0.05), and both were higher than that in no intervention group (162±4 cm, < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. Long term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.
Adolescent ; Body Height ; Bone Development ; Child ; Gonadotropin-Releasing Hormone ; Growth Disorders ; Humans ; Letrozole ; therapeutic use ; Male

OBJECTIVE: To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD). METHODS: Clinical data of 12 male DSD children with a mean age of 14.6±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients were treated with letrozole (1.25-2.5 mg, once a day) for 3 months or longer, and followed up for 0.5-2.5 years. Clinical manifestation and laboratory test findings were documented, and the efficacy and safety were evaluated. RESULTS: After half-year treatment, the blood luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels of patients increased (all < 0.05), and estrogen levels decreased from baseline ( < 0.05). After 1 year of treatment, the blood testosterone level was significantly higher ( < 0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease, but there was no significant statistical difference ( >0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant changes in biochemical results after treatment, and no significant adverse event was observed during the treatment. CONCLUSIONS Letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.
Adolescent ; Child ; Disorders of Sex Development ; drug therapy ; Follicle Stimulating Hormone ; Humans ; Letrozole ; therapeutic use ; Luteinizing Hormone ; Male ; Retrospective Studies ; Testosterone