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Background and Aims Alterations in the androgen sensitivity pathway have been identified in severely undermasculinized boys, and mutations of the androgen-receptor gene (AR) are usually found in partial or complete androgen insensitivity syndrome. The aim of this study was to determine whether even the most minor forms of isolated hypospadias are associated with AR mutations and thus whether all types of hypospadias warrant molecular analysis of the AR. Methods 292 Caucasian children presenting with isolated hypospadias (no micropenis, no cryptorchidism) and 345 controls were included prospectively. Mutational analysis of the AR through direct sequencing (exons 1–8) was performed. Results Five missense mutations of the AR were identified in 9 patients with glandular or penile anterior (n=5), penile midshaft (n=2) and penile posterior (n=2) hypospadias, i.e., 3%: p.Q58L (c.1288 A>T), 4 cases of p.P392S (c.2289 C>T), 2 cases of p.A475V (c.2539 C>T), p.D551H (c.1651 G>C) and p.Q799E (c.3510 C>G). None of these mutations was present in the control group. Four mutations are novel findings since 1 has never been reported to date (p.D551H) and 3 have never been reported in patients with genital malformation but only in isolated infertility: p.Q58L, p.P392S, and p.A475V. It is notable that micropenis, a cardinal sign of AIS, was not present in any patients. Conclusion AR mutations may play a role in the cause of isolated hypospadias, even in the most minor forms. Identification of this underlying genetic alteration is important for proper diagnosis and may significantly improve the follow-up of these patients during puberty, especially regarding future fertility.

Background and Aim Bilateral surgery was formerly advocated in premature boys with unilateral inguinal hernia to avoid a metachronous contralateral hernia and the risks of recurrent anesthesia. But the recent progress in pediatric anesthesia and the demonstrated morbidity of herniotomy during the neonatal period on fertility now question this attitude. We aimed to compare the morbidity of preventive bilateral vs elective unilateral herniotomy in premature boys with unilateral hernia and to evaluate the incidence of contralateral metachronous hernia. Methods Retrospective multicenter analysis of 966 premature boys presenting with unilateral inguinal hernia. 558 infants benefited from unilateral herniotomy and 408 from bilateral herniotomy with a median follow up of 20 months. Results The rate of contralateral metachronous hernia after unilateral surgery was 11% (10% on right vs 13% on left). Morbidity on the contralateral side was higher in case of preventive bilateral surgery than in metachronous hernia (2% vs 0.2% p=0.003), especially for testicular hypotrophy (0.70% vs 0.18 %, p= 0.3) and secondary cryptorchidism (1% vs 0%, p=0.03) Comparison between the type anesthesias (general anesthesia versus central block) did not show significant differences depending on the type of care (unilateral or bilateral, planned or emergency). Conclusion Systematic bilateral herniotomy is unnecessary in almost 90% of patients and has a higher morbidity than secondary surgery for metachronous hernia. These results, along with the risk of deferential damage and hypofertility reported in later adulthood, justify treating only the symptomatic side in premature boys.