Gynecomastia and Its Management In Boys With Partial Androgen Insensitivity Syndrome.

INTRODUCTION: Partial androgen insensitivity syndrome (PAIS) is a rare condition that is reported to be commonly associated with gynecomastia in males. OBJECTIVES: To assess the management of gynecomastia in male PAIS. MATERIALS AND METHODS: Retrospective review of males with PAIS over the age of 10 years in the I-DSD registry. RESULTS: Of the 205 eligible cases, information was available for 57 from 13 centers. An androgen receptor gene variant was confirmed in 45 (79%) with a median age at first presentation of 1.0 year (range 0.1, 26.0). Of the 45 genetically confirmed cases, gynecomastia was present in 41 (91%) with a median age at the time of gynecomastia development of 13.5 years (11.0, 29.0). In the other 4 (9%) with no gynecomastia, the median age at last assessment was 15.7 years (10.6, 17.0). In 30 cases with information available, micropenis was present at the time of gynecomastia development in 23 (77%). Of the 35 with information available, 2 (6%) exhibited spontaneous resolution between the ages of 15 and 21 years and 25 (71%) had breast surgery at a median age of 15.7 years (14.0, 23.0). Of these 25, 9 (26%) had previously received medical therapy. The median clinician score of effectiveness for medical therapy was 3 (1, 8) compared to 10 (3, 10) for surgery (P < .0001). In 31 with information available, 13 (42%) had received psychology support. CONCLUSION: Gynecomastia is common in PAIS but not universal. Surgical management may be more effective than medical therapy, but there is a need for further standardized and systematic studies.

Disorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic Findings.

Background: The clinical profile and genetics of individuals with Disorders/Differences of Sex Development (DSD) has not been reported in Ukraine. Materials and Methods: We established the Ukrainian DSD Register and identified 682 DSD patients. This cohort includes, 357 patients (52.3% [303 patients with Turner syndrome)] with sex chromosome DSD, 119 (17.5%) with 46,XY DSD and 206 (30.2%) with 46,XX DSD. Patients with sex chromosome DSD and congenital adrenal hyperplasia (CAH, n=185) were excluded from further studies. Fluorescence in situ hybridization (FISH) was performed for eight 46,XX boys. 79 patients underwent Whole Exome Sequencing (WES). Results: The majority of patients with 46,XY and 46,XX DSD (n=140), were raised as female (56.3% and 61.9% respectively). WES (n=79) identified pathogenic (P) or likely pathogenic (LP) variants in 43% of the cohort. P/LP variants were identified in the androgen receptor (AR) and NR5A1 genes (20.2%). Variants in other DSD genes including AMHR2, HSD17B3, MYRF, ANOS1, FGFR11, WT1, DHX37, SRD5A1, GATA4, TBCE, CACNA1A and GLI2 were identified in 22.8% of cases. 83.3% of all P/LP variants are novel. 35.3% of patients with a genetic diagnosis had an atypical clinical presentation. A known pathogenic variant in WDR11, which was reported to cause congenital hypogonadotropic hypogonadism (CHH), was identified in individuals with primary hypogonadism. Conclusions: WES is a powerful tool to identify novel causal variants in patients with DSD, including a significant minority that have an atypical clinical presentation. Our data suggest that heterozygous variants in the WDR11 gene are unlikely to cause of CHH.

Risk Factors for Childhood Overweight and Obesity in Ukraine and Germany

Objective: The prevalence of overweight and obesity in childhood and adolescence are rapidly increasing and influenced by genetic, familial, environmental, socioeconomic and cultural factors. The aim of the study was to compare risk factors for childhood obesity in Ukraine (UA) and Germany (DE) using comparable investigative tools. Methods: Two groups of children, aged 8 to 18 years, from DE (93 children) and UA (95 children) were divided into overweight and obese groups. Anthropometric data and detailed medical history were collected. Results: Risk factors in pregnancy (prematurity, weight gain >20 kg, early contractions) were equally frequent in both groups. Positive correlations of body mass index (BMI)-standard deviation score (SDS) between children and mothers were noted. The proportion of family members with diabetes mellitus was lower in the UA group. Obesity was more frequent at one year of age in DE children. The DE group also became overweight at an earlier age and remained overweight over a longer period of time compared to UA. The mean BMI-SDS of obese children was lower in the UA group. In both groups waist circumference to height ratio was >0.5, indicating presence of a cardiometabolic risk factor. About half of the patients in both groups had blood pressure values exceeding the 95th percentile. Conclusion: Similar risk factors for obesity were observed among two groups of children in UA and DE. Differences were observed regarding the prevalence of specific risk factors for childhood obesity. Population-specific distribution of risk factors needs to be considered in order to optimize prevention and treatment strategies.