New frontiers on the molecular underpinnings of hypospadias according to severity.

Hypospadias, which is characterised by the displacement of the urethral meatus from its typical anatomical location in males, shows various degrees of severity. In this systematic review, we surveyed our current understanding of the genetics of isolated hypospadias in humans according to the severity of the condition. We found that sequencing and genotyping approaches were the preferred methods of study and that single nucleotide polymorphisms were the most common finding associated with hypospadias. Most genes fell into four gene-pathway categories related to androgens, oestrogens, growth factors, or transcription factors. Few hypospadias studies classify their findings by severity. Taken together, we argue that it is advantageous to take into consideration the severity of the condition in search of novel candidates in the aetiology of hypospadias. Abbreviations: AR: androgen receptor; ATF3: activating transcription factor 3; BMP4: bone morphogenetic protein 4; BMP7: bone morphogenetic protein 7; CYP17: steroid 17-alpha-hydroxylase/17,20 lyase; CYP1A1: cytochrome P450 1A1; CYP3A4: cytochrome P450 3A4; CNVs: copy number variants; DGKK: diacylglycerol kinase kappa; ESR1: oestrogen receptor 1; ESR2: oestrogen receptor 2; FGF8: fibroblast growth factor 8; FGF10: fibroblast growth factor 10; FGFR2: fibroblast growth factor receptor 2; HOXA4: homeobox protein Hox-A4; HOXB6: homeobox protein Hox-B6; HSD17B3: hydroxysteroid 17-beta dehydrogenase 3; MAMLD1: mastermind-like domain-containing protein 1; SF-1: splicing factor 1; SHH: sonic hedgehog; SNPs: single nucleotide polymorphisms; SOX9: SRY-box 9; SRD5A2: steroid 5 alpha-reductase 2; SRY: sex-determining region Y protein; STAR: steroidogenic acute regulatory protein; STARD3: StAR-related lipid transfer protein 3; STS: steryl-sulfatase; WT1: Wilms tumour protein; ZEB1: zinc finger oestrogen-box binding homeobox 1.

Evaluation and Management of the Undescended Testis in Puerto Rico: A Single Surgeon's 10 Years of Experience.

OBJECTIVE: Cryptorchidism is an abnormality of the male genitourinary tract in which one or both testes fail to descend into the scrotum. The American Urological Association (AUA) clinical guidelines for the evaluation and treatment of cryptorchidism were recently published. We reviewed our experience with the evaluation and management of our patients and examined our findings with respect to the AUA and European Association of Urology (EAU) guidelines. METHODS: Data were obtained from pediatric patients who underwent a surgical intervention for an undescended testis from 2007 through 2017 at HIMA Hospital and the University Pediatric Hospital (both in Puerto Rico); all the surgeries were performed by the same surgeon. A total of 754 patients were identified; 142 patients were excluded due to lack of follow-up data (N = 612). The data obtained included age, testes locations, radiologic and surgical findings, and postoperative results. RESULTS: At their initial evaluations, a large proportion of the patients (46.4%) came accompanied with radiographic imaging. These findings were consistent with those of the physical examination in 58.5% of the patients and with the surgical findings in 63.1% (sensitivity 77.9%, specificity 45.8%). Our data showed that the median referral age was 24 months, which suggests that there was a significant delay in diagnosis. At the time of surgery, the average age of the patients who required an orchiectomy was 3.93 years, while those who underwent an orchiopexy had an average age of 3.28 years. CONCLUSION: Our data reveal that, despite its lack of usefulness, radiologic imaging continues to be included in the diagnostic workups of children newly identified with cryptorchidism in Puerto Rico. In addition, and contrary to the guidelines, there tends to be a significant delay in treatment with surgical intervention. It is important to continue to educate our referring physicians on the AUA and EUA guidelines in order to create awareness and encourage the proper diagnostic and treatment approach for cryptorchidism.

Age of the mother as a risk factor and timing of hypospadias repair according to severity.

BACKGROUND & OBJECTIVES: Hypospadias is characterized by a displacement of the urethral opening in males that can change from the typical position within the glans penis to a subcoronal position (Type I), to anywhere along the ventral shaft (Type II), to penoscrotal, scrotal, or perineal positions (Type III). We and others have previously reported that age of the mother (≥ 40 years old) is a risk factor for having a child with hypospadias, but there is a scarcity of reports on whether such risk is higher for having a child with the mild (Type I) or the more severe forms (Types II and III). In addition, we aimed to assess the timing of hypospadias repair according to severity. METHODS: Parents of children with hypospadias were interviewed by using a series of questionnaires (n = 128 cases). Severity was confirmed in the clinic and age of the mother was self-reported. Number of surgeries, age of child by the first and the last intervention was also assessed. Ordered logistic regression and the Brant test were employed to calculate risk between mild (Type I) and severe cases (Types II and III), and the assumption of proportional odds, respectively. The Mann-Whitney U Test was used to compare number of surgeries and age by the last repair between mild and severe cases. One-way ANOVA was employed to compare age of the child at the time of first surgery across severities (Types I - III). RESULTS: Women ≥ 40 years of age are 3.89 times [95% CI: 1.20-12.64] at a higher risk for having a child with the more severe forms of the condition than younger women. Repair of Type I was accomplished with 1 intervention whereas more severe cases required 1 - 4 (2 ± 0.5) surgical interventions. The timing for hypospadias repair of Type I cases occurred at an average age of 16.2 ± 4.88 months, of Type II cases occurred at an average age of 20.3 ± 8.15 months whereas the average age of the first hypospadias repair among Type III cases was 12.68 ± 2.52 months. Number of surgeries according to severity (p ≤ 0.0018, z-ratio = 2.91) and age difference for the timing of last repair (p ≤ 0.045, z-ratio = 1.69) were statistically different, but not the age difference for the first repair. CONCLUSIONS: Increased maternal age is associated with the most severe forms of hypospadias. There is room for improvement for the timing of hypospadias repair according to severity.