Hypospadias: a review
DOI:
https://doi.org/10.18203/2320-6012.ijrms20232483Keywords:
External genital development, Pediatric surgery, Pediatric urology, Hypospadias, Hypospadias repair, Hypospadias complicationsAbstract
Hypospadias is a congenital malformation of the male external genitalia, which includes: anomalous location proximal to the urethral meatus, in any portion of the glans penis and perineum, hooded dorsal foreskin, and inverted penile curvature on the dorsal side of the foreskin. The etiology has been considered multifactorial, secondary to the interaction of environmental factors with specific genetic background. It represents the second most frequent congenital defect in male newborns. It has increasing prevalence rates of 0.25 new cases per 10,000 newborns per year. Risk factors that have been identified include infants small for gestational age with weight below the 10th percentile, head length and/or circumference, intrauterine growth restriction, and placental insufficiency. Regarding environmental risk factors, maternal exposure to pesticides has been linked. Prenatal diagnosis has been described, however proximal hypospadias is usually detected, making it difficult to diagnose distal hypospadias using this method. So usually the diagnosis is made after birth during the physical examination. To date, more than 300 surgical techniques are known for the correction of hypospadias. The treatment of distal hypospadias is currently performed in one time; the management of proximal hypospadias is controversial; one group favors the one-stage procedure, while other groups choose to perform the two-stage procedure.
References
Cimador M, Vallasciani S, Manzoni G, Rigamonti W, De Grazia E, Castagnetti M. Failed hypospadias in paediatric patients. Nat Rev Urol. 2013;10(11):657-66.
Fernandez N, Chua M, Villanueva J, Varela D, Bagli D, Shnorhavorian M. Neural network non-linear modeling to predict hypospadias genotype-phenotype correlation. J Pediatr Urol. 2023;19(3):288.
Halaseh SA, Halaseh S, Ashour M. Hypospadias: A Comprehensive Review Including Its Embryology, Etiology and Surgical Techniques. Cureus. 2022;14(7):e27544.
Govers LC, Phillips TR, Mattiske DM, Rashoo N, Black JR, Sinclair A, et al. A critical role for estrogen signaling in penis development. FASEB J. 2019;33(9):10383-92.
Blaschko SD, Cunha GR, Baskin LS. Molecular mechanisms of external genitalia development. Differentiation. 2012;84(3):261-8.
Inanc I, Avlan D, Eker D, Gurkan H. A Genetics Study in the Foreskin of Boys with Hypospadias. Mol Syndromol. 2023;14(3):185-90.
Kaefer M, Rink R, Misseri R, Winchester P, Proctor C, Ben Maamar M, et al. Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations. Sci Rep. 2023;13(1):555.
Yu X, Nassar N, Mastroiacovo P, Canfield M, Groisman B, Bermejo-Sanchez E, et al. Hypospadias prevalence and trends in international birth defect surveillance systems. Eur Urol. 2019;76(4):482-49.
Duckett JW Jr. Hypospadias. Pediatr Rev. 1989;11(2):37-42.
Hussain N, Chaghtai A, Herndon CD, Herson VC, Rosenkrantz TS, McKenna PH: Hypospadias and early gestation growth restriction in infants. Pediatrics. 2002;109:473-8.
Gaspari L, Paris F, Jandel C, Kalfa N, Orsini M, Daures JP, et al. Prenatal environmental risk factors for genital malformations in a population of 1442 French male newborns: a nested case control study. Hum Reprod. 2011;26(11):3155-62.
Das D, Dutta HK, Borbora D, Brahma RC, Das JM. Assessing the relationship between hypospadias risk and parental occupational exposure to potential endocrine-disrupting chemicals. Occup Environ Med. 2023;80(2):93-6.
Zhou Y, Huang F, Liu Y, Li D, Zhou Y, Shen L, et al. TGF-β1 relieves epithelial–mesenchymal transition reduction in hypospadias induced by DEHP in rats. Pediatr Res. 2019;87(4):639-46.
Wang CH, Zeng Q, Jiang XZ, Wan B, He LY. Distribution of HoxA13 in the prepuce and urethral plate in different types of hypospadias and its implication. Zhonghua Nan Ke Xue. 2013;19(9):806-10.
Samtani R, Bajpai M, Vashisht K, Ghosh PK, Saraswathy KN. Hypospadias risk and polymorphism in SRD5A2 and CYP17 genes: case-control study among Indian children. J Urol. 2011;185(6):2334-9.
Wang Y, Li Q, Xu J, Liu Q, Wang W, Lin Y, et al. Mutation analysis of five candidate genes in Chinese patients with hypospadias. Eur J Hum Genet. 2004;12(9):706-12.
Beleza-Meireles A, Tohonen V, Soderhall C, Schwentner C, Radmayr C, Kockum I, et al. Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias. Eur J Endocrinol. 2008;158(5):729-39.
Kalfa N, Liu B, Klein O, Wang MH, Cao M, Baskin LS. Genomic variants of ATF3 in patients with hypospadias. J Urol. 2008;180(5):2183-8.
Beleza-Meireles A, Kockum I, Lundberg F, Soderhall C, Nordenskjold A. Risk factors for hypospadias in the estrogen receptor 2 gene. J Clin Endocrinol Metab. 2007;92(9):3712-8.
Beleza-Meireles A, Lundberg F, Lagerstedt K, Zhou X, Omrani D, Frisen L, et al. FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. Eur J Hum Genet. 2007;15(4):405-10.
Liu B, Agras K, Willingham E, Vilela ML, Baskin LS. Activating transcription factor 3 is estrogen-responsive in utero and upregulated during sexual differentiation. Horm Res. 2006;65(5):217-22.
Petiot A, Perriton CL, Dickson C, Cohn MJ. Development of the mammalian urethra is controlled by Fgfr2-IIIb. Development. 2005;132(10):2441-50.
Geller F, Feenstra B, Carstensen L, Pers TH, van Rooij IA, Körberg IB. Genome-wide association analyses identify variants in developmental genes associated with hypospadias. Nat Genet. 2014;46(9):957-63.
Priyadarshi V, Singh JP, Mishra S, Vijay MK, Pal DK, Kundu AK: Prostatic utricle cyst: a clinical dilemma. APSP J Case Rep. 2013;4:16.
Uygur L, Sivrikoz TS, Kalelioglu IH, Has R, Isguder CK, Oktar T, et al. Predictive value of ultrasound in prenatal diagnosis of hypospadias: hints for accurate diagnosis. J Perinat Med. 2023;1-8.
Keays MA, Dave S. Current hypospadias management: Diagnosis, surgical management, and long-term patient-centred outcomes. Can Urol Assoc J. 2017;11(1-2):S48-53.
Cox MJ, Coplen DE, Austin PF. The incidence of disorders of sexual differentiation and chromosomal abnormalities or cryptorchidism and hypospadias stratified by meatal location. J Urol. 2008;180:2649-52.
Bhat A, Mandal AK. Acute postoperative complications of hypospadias repair. Indian J Urol. 2008;24(2):241-8.
Duarsa GWK, Tirtayasa PMW, Daryanto B, Nurhadi P, Renaldo J, Tarmono T, et al. Common Practice of Hypospadias Management by Pediatric Urologists in Indonesia: A Multicenter Descriptive Study from Referral Hospitals. Open Access Maced J Med Sci. 2019;7(14):2242-5.
Arlen AM, Kirsch AJ, Leong T, Broecker BH, Smith EA, Elmore JM. Further analysis of the Glans-Urethral Meatus-Shaft (GMS) hypospadias score: correlation with postoperative complications. J Pediatr Urol. 2015;11:1-5.
Shoukry A, Abbas A, Abdelwahab M, Ghoneima W, Shouman A, El Ghoneimy M, et al. Glans–urethral meatus–shaft score and penile parameters as preoperative assessment tools for hypospadias surgery outcome. Afr J Urol. 2021;27(1):1-8.
Immergut M, Boldus R, Yannone E, Bunge R, Flocks R. The local application of testosterone cream to the prepubertal phallus. J Urol. 1971;105(6):905-6.
Bhat A. General considerations in hypospadias surgery. Indian J Urol. 2008;24(2):188-94.
Manzoni G, Bracka A, Palminteri E, Marrocco G. Hypospadias surgery: when, what and by whom? BJU Int. 2004;94(8):1188-95.
Castagnetti M, El-Ghoneimi A. Surgical management of primary severe hypospadias in children: an update focusing on penile curvature. Nat Rev Urol. 2022;19(3):147-60.
Springer A, Krois W, Horcher E. Trends in hypospadias surgery: results of a worldwide survey. Eur Urol. 2011;60(6):1184-9.
Weber BA, Braga LH, Patel P, Pippi Salle JL, Bägli DJ, Khoury AE, et al. Impact of penile degloving and proximal ventral dissection on curvature correction in children with proximal hypospadias. Can Urol Assoc J. 2014;8(11-12):424-7.
Roshandel MR, Aghaei Badr T, Kazemi Rashed F, Salomon S, Ghahestani SM, Ferrer FA. Hypospadias in toddlers: a multivariable study of prognostic factors in distal to mid-shaft hypospadias and review of literature. World J Pediatr Surg. 2022;5(1):e000225.
Khalil M, Gharib T, El-Shaer W, Sebaey A, Elmohamady B, Elgamal K. Mathieu technique with incision of the urethral plate versus standard tubularised incised-plate urethroplasty in primary repair of distal hypospadias: A prospective randomised study. Arab J Urol. 2017;15(3):242-7.
Djordjevic ML, Majstorovic M, Stanojevic D, Bizic M, Kojovic V, Vukadinovic V, et al. Combined buccal mucosa graft and dorsal penile skin flap for repair of severe hypospadias. Urology. 2008;71(5):821-5.
Zu J, Chen Y, Liu Y, He T, Wang Y, Zu Y, et al. Neomodified Koyanagi technique for severe hypospadias with one-stage sealed Y-shaped penis foreskin vascular protection surgery. Clin Case Rep. 2022;10(3):e05575.
Badawy H, Orabi S, Hanno A, Abdelhamid H. Posterior hypospadias: Evaluation of a paradigm shift from single to staged repair. J Pediatr Urol. 2018;14(1):28.
Gozar H, Bara Z, Dicu E, Derzsi Z. Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review). Exp Ther Med. 2023;25(5):211.
Al-Adl AM, Abdel Aal AM, El-Karamany TM, Noureldin YA. Two-stage repair of proximal hypospadias with moderate to severe chordee using inner preputial skin graft: prospective evaluation of functional and cosmetic outcomes. World J Urol. 2020;38(11):2873-9.
Steven L, Cherian A, Yankovic F, Mathur A, Kulkarni M, Cuckow P. Current practice in paediatric hypospadias surgery; a specialist survey. J Pediatr Urol. 2013;9(6):1126-30.
Blanc T, Peycelon M, Siddiqui M, Muller C, Paye-Jaouen A, El-Ghoneimi A. Double-face preputial island flap revisited: is it a reliable one-stage repair for severe hypospadias? World J Urol. 2002;39(5):1613-24.
Fernandez N, Maxwell A, Noonavath M, Shnorhavorian M. Comprehensive multidisciplinary phenotyping of patients with hypospadias. A pilot study. J Pediatr Urol. 2023;1477-5131.
Di H, Wen Y, Li Y. Preoperative hormone therapy in single-stage repair of hypospadias: A comprehensive systematic review. J Pediatr Urol. 2023;19(3):250-60.
Cooper CS, Lockwood GM, Edwards AB, Perry SS, Storm DW. What is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee. J Pediatr Urol. 2023;e1-9.
Villanueva CA. Ventral penile curvature estimation using an app. J Pediatr Urol. 2020;16(4):437.
Aldabek K, Luketich S, Abdelhalim A, Elbakry A, Al-Omar O. Double versus single diaper technique after hypospadias repair, does it really matter? J Pediatr Urol. 2023;23:227-9.
