Background: Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A DHH variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications.Case presentation: Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the SRY gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in DHH exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers.Conclusion: In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a DHH homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.

Abstract Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT.Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital 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 separately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA.Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). 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 advanced BA. In the multiple linear regression model, 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 was significantly higher than that of normal weight and overweight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher 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.

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age, but IPT girls requiring further investigations show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT. Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were divided into two groups with advanced BA of 2 years as the cutoff. 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 seperately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA. Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). IGF-1 SDS (OR=1.642, p＜0.001) and DHEAS SDS (OR=1.125, p=0.021) were independent risk factors for advanced BA. In the multiple linear regression model, IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 18.9% 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 BA advancement in obesity was significantly higher than that of normal weight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affect BA advancement independent of BMI SDS. Conclusions: Chinese girls aged 4-8 years with IPT requiring further investigations 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.

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.