Hypospadias

Hypospadias is one of the most common congenital anomalies in men. The condition is typically characterized by proximal displacement of the urethral opening, penile curvature, and a ventrally deficient hooded foreskin. In about 70%, the urethral meatus is located distally on the penile shaft; this is considered a mild form that is not associated with other urogenital deformities. The remaining 30% are proximal and often more complex. In these cases, endocrinological evaluation is advised to exclude disorders of sexual differentiation, especially in case of concomitant unilateral or bilateral undescended testis. Although the etiology of hypospadias is largely unknown, many hypotheses exist about genetic predisposition and hormonal influences. The goal of hypospadias repair is to achieve cosmetic and functional normality, and currently, surgery is recommended between 6 and 18 months of age. Hypospadias can be corrected at any age with comparable complication risk, functional, and cosmetic outcome; however, the optimal age of repair remains conclusive. Although long-term overall outcome concerning cosmetic appearance and sexual function is fairly good, after correction, men may more often be inhibited in seeking sexual contact. Moreover, lower urinary tract symptoms occur twice as often in patients undergoing hypospadias repair and can still occur many years after the initial repair.ConclusionThis study explores the most recent insights into the management of hypospadias. What is Known: • Guidelines advise referral for treatment between 6 and 18 months of age. • Cosmetic outcome is considered satisfactory in over 70% of all patients. What is New: • Long-term complications include urinary tract symptoms and sexual and cosmetic issues. • New developments allow a more individualized approach, hopefully leading to less complications and more patient satisfaction.

Male reproductive health has declined as indicated by increasing rates of cryptorchidism, i.e., undescended testis, poor semen quality, low serum testosterone level, and testicular cancer. Exposure to endocrine disrupting chemicals (EDCs) has been proposed to have a role in this finding. In utero exposure to antiandrogenic EDCs, particularly at a sensitive period of fetal testicular development, the so-called 'masculinization programming window (MPW)', can disturb testicular development and function. Low androgen effect during the MPW can cause both short- and long-term reproductive disorders. A concurrent exposure to EDCs may also affect testicular function or damage testicular cells. Evidence from animal studies supports the role of endocrine disrupting chemicals in development of male reproductive disorders. However, evidence from epidemiological studies is relatively mixed. In this article, we review the current literature that evaluated relationship between prenatal EDC exposures and anogenital distance, cryptorchidism, and congenital penile abnormality called hypospadias. We review also studies on the association between early life and postnatal EDC exposure and semen quality, hypothalamic-pituitary-gonadal axis hormone levels and testicular cancer.

The scalp-ear-nipple (SEN) syndrome is an autosomal-dominant disorder characterized by cutis aplasia of the scalp and malformations of breast, external ears, digits, and nails. Genetic analyses have shown that the disease is caused by missense mutations of the KCTD1 protein, although the functional/structural basis of SEN insurgence is hitherto unknown. With the aim of unravelling the molecular basis of the SEN syndrome associated with KCTD1 mutations we here expressed and characterized several disease causing mutants. A preliminary dissection of the protein provides insights into the role that individual domains play in KCTD1 stability. The characterization of SEN-causing mutants indicates that, although the mutation sites are located in distant regions of the BTB domain or of the pre-BTB region, all of them are unable to interact with the transcription factor AP-2α, a well-known KCTD1 biological partner. Notably, all mutations, including the one located in the pre-BTB region, produce a significant destabilization of the protein. The structural role of the pre-BTB region in KCTD1 and other proteins of the family is corroborated by its sequence conservation in orthologs and paralogs. Interestingly, SEN-causing mutations also favor the tendency of KCTD1 to adopt structural states that are characterized by the ability to bind the β-amyloid fluorescent dye thioflavin T. The formation of aggregation-prone species may have important implications for the disease etiology. Collectively, these findings provide an intriguing picture of the functional and structural alterations induced by KCTD1 mutations that ultimately lead to disease.

BackgroundHypospadias is a common congenital malformation requiring surgery. Caregivers face substantial perioperative information needs, and large language models (LLMs) offer a potential health education channel, but their performance in pediatric urology and the relation between citation accuracy and clinical content safety lack systematic evaluation.ObjectiveThis study aimed to evaluate 5 LLMs (ChatGPT-4o, Gemini-2.5-Pro, OpenEvidence, Zhipu Qingyan, and DeepSeek) for pediatric hypospadias perioperative consultation, and to characterize the dimensions clinicians and caregivers prioritize.MethodsA noninterventional cross-sectional study was conducted at a tertiary hospital in April 2025. From a 40-item bank, 10 high-priority questions were selected by an independent caregiver screening cohort (N=34, cohort A) and classified into 3 risk levels. Twenty-three pediatric urology experts (6 dimensions) and 36 primary caregivers (cohort B; 4 dimensions) evaluated responses by double-blind forced-ranking (reverse-scored, 5=best). Friedman tests with Kendall W assessed overall differences; paired Wilcoxon tests with Bonferroni correction (adjusted α=.005) and rank-biserial r with Hodges-Lehmann 95% CIs were used post hoc. Reference authenticity was independently verified by 2 reviewers (XH and WH) using a 5-category scheme (V/PV/F/G/NR [V: Verifiable, PV: Partially Verifiable, F: Fabricated, G: Guideline-Based, Nonspecific, and NR: No References]), with consensus after canonical-source reverification (Cohen κ=0.702 preadjudication). An 8-reviewer clinical safety audit (7 senior specialists plus 1 European Association of Urology [EAU]-anchored intermediate-title clinician) applied a 4-level severity scheme (None/Mild/Moderate/Severe).ResultsModels differed significantly (caregiver: χ²4=77.5, W=0.538, PConclusionsHigh citation accuracy does not guarantee clinical safety. In the first dual-perspective evaluation, no model was uniformly best. Gemini-2.5-Pro was most comprehensive but relied on nonspecific guidelines. DeepSeek scored highest on caregiver-rated Empathy, yet it had the highest fabrication rate. OpenEvidence produced the most verifiable citations but carried the heaviest Severe-flag burden. These dimension-level priorities, the dissociation between citation quality and safety, and the portable evaluation framework can inform future pediatric medical-artificial intelligence (AI) development. For perioperative use, AI should follow a tiered human-machine collaboration model with mandatory clinician oversight in high-risk scenarios.