OBJECTIVE: To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD). METHODS: A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children. RESULTS: In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation. CONCLUSION Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.
Humans ; Male ; Female ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Cryptorchidism ; Hypospadias ; Retrospective Studies ; Quality of Life ; Sex Chromosome Aberrations ; Karyotyping ; Mosaicism ; Disorders of Sex Development/genetics*

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) ( P = 0.008) and the average number of operation required to cure ( P < 0.001) between one-stage and staged operations. PHS had a positive effect ( P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.
Male ; Humans ; Child ; Infant ; Hypospadias/surgery* ; Retrospective Studies ; Oxidoreductases ; Postoperative Complications ; Genetic Association Studies

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
Male ; Humans ; Child ; Disorders of Sex Development/pathology* ; Hypospadias/complications* ; Cryptorchidism/complications* ; Retrospective Studies ; Adrenal Hyperplasia, Congenital ; Steroid 21-Hydroxylase

Urethrocutaneous fistula may complicate hypospadias repair. We noticed that double-layered preputial dartos flaps added to tubularized incised plate urethroplasty can reduce the risk of urethrocutaneous fistula. The aim of this study was to compare the outcomes of tubularized incised plate urethroplasty with double-layered preputial dartos flaps to with single-layered local fascial flaps in preventing urethrocutaneous fistula. A retrospective cohort study was conducted between January 2017 and December 2020 at Jordan University Hospital (Amman, Jordan). Boys who were aged between 6 months and 5 years, diagnosed with distal hypospadias, and not circumcised were included. The primary outcome was the occurrence of urethrocutaneous fistula in patients who underwent tubularized incised plate urethroplasty with a double-layered fascial flap. The results showed a total of 163 boys with distal hypospadias; among them, 116 patients underwent tubularized incised plate urethroplasty with a single-layered fascial flap, and 47 underwent tubularized incised plate urethroplasty with a double-layered fascial flap. The development of urethrocutaneous fistula was higher in the group receiving tubularized incised plate urethroplasty with a single-layered fascial flap than in the group receiving tubularized incised plate urethroplasty with a double-layered fascial flap after 1 month, 6 months, and 12 months (6.9% vs 0, 10.3% vs 0, and 5.2% vs 0, respectively), and the difference after 6 months was statistically significant (P = 0.02).
Male ; Humans ; Infant ; Hypospadias/surgery* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Urethra/surgery* ; Fistula/surgery* ; Treatment Outcome

Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.
Child ; Female ; Humans ; Hypospadias/surgery* ; Infant ; Male ; Retrospective Studies ; Treatment Outcome ; Urethra/surgery* ; Urologic Surgical Procedures, Male/methods*

Male ; Humans ; Hypospadias/surgery* ; Urologic Surgical Procedures, Male ; Urethra/surgery*

Male ; Humans ; Infant ; Hypospadias/surgery* ; Urologic Surgical Procedures, Male ; Urethra/surgery* ; Penis/surgery* ; Follow-Up Studies

Male ; Humans ; Penile Neoplasms/surgery* ; Constriction, Pathologic/surgery* ; Urethral Stricture/surgery* ; Surgical Flaps/surgery* ; Amputation, Surgical ; Penis/surgery* ; Plastic Surgery Procedures ; Hypospadias/surgery*

Urethral plate (UP)-preserving urethroplasty is simple and has few complications, but it may affect the development of penis in the long term and lead to recurrent chordee. In this study, we used obliquely cut UP to repair hypospadias with mild chordee after degloving (15°-30°) and compared the results with onlay urethroplasty to explore its rationality and feasibility. Between April 2018 and October 2020, 108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty. Clinical data were prospectively collected, and medium-term outcomes were assessed at follow-up. The complications were compared between the two groups. Forty-four patients underwent the modified onlay procedure (Group I), with follow-up time (mean ± standard deviation [s.d.]) of 23.2 ± 4.5 (range: 17-31) months. Sixty-four patients underwent a standard onlay procedure (Group II), with follow-up time (mean ± s.d.) of 39.7 ± 3.9 (range: 32-46) months. There was no difference in age at surgery. The urethral defect length and operative time were longer in Group I. Six cases of fistula and one case each of stricture and diverticulum were reported in Group I. In Group II, 11 cases of fistula and one case each of stricture and diverticulum were reported. The complication rates were 18.2% and 20.3% in Group I and Group II, respectively (P > 0.05). These medium-term follow-up results demonstrate that the modified onlay procedure (oblique cut UP urethroplasty) is a safe and feasible technique for hypospadias with mild chordee after degloving. Compared with standard onlay urethroplasty, this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications.
Male ; Humans ; Infant ; Hypospadias/surgery* ; Cicatrix/surgery* ; Constriction, Pathologic/surgery* ; Urethra/surgery* ; Diverticulum ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*