The Intersection of Androgen Insensitivity Syndrome and Anorectal Malformations
Özet
Androgen Insensitivity Syndrome is a form of 46,XY disorder of sex development caused by mutations in the androgen receptor (AR) gene, leading to partial or complete resistance to androgen action and a variable spectrum of undervirilisation. Clinical phenotypes range from complete female external genitalia to varying degrees of ambiguous genitalia and undervirilisation in males, depending on residual receptor function. The classification and diagnostic framework for AIS, including differentiation into complete, partial, and mild forms, is well established in the literature [1]. The management of AIS and other disorders of sex development requires a structured multidisciplinary approach involving pediatric endocrinology, urology, genetics, psychology, and specialised nursing care. This multidisciplinary model is strongly recommended in established clinical guidelines for the management of infants with ambiguous genitalia [2]. This chapter will also explore the uncommon but clinically important co-occurrence of Anorectal Malformations and Androgen Insensitivity Syndrome, focusing on their diagnostic challenges, embryological considerations, and implications for multidisciplinary neonatal management.
Referanslar
Hughes, I.A., et al. (2012). “Androgen insensitivity syndrome.” The Lancet, 380(9851), 1419– 1428.
Warne, G.L., & Grover, S. (2005). “Disorders of sex development: the management of the child with ambiguous genitalia.” Journal of Paediatric Child Health, 41(5), 232–237.
Hutson, J.M., et al. (2014). “Disorders of Sex Development: An Integrated Approach.” Spring- er.
Levitt, M.A., & Peña, A. (2007). “Anorectal malformations.” Orphanet Journal of Rare Diseas- es, 2(1), 33.
Lee, P.A., et al. (2006). “Consensus statement on management of intersex disorders.” Pediat- rics, 118(2), e488–e500.
Gottlieb, B., et al. (2012). “Androgen Insensitivity Syndrome.” GeneReviews®.
Al-Samahy, A.S., et al. (2019). “Management of scrotal hypoplasia in DSD.” Journal of Pediat- ric Urology.
Wong, M., & Hutson, J. M. (2010). “The embryological and clinical link between the urogen- ital sinus and the rectum.” Journal of Pediatric Surgery.
Ahmed, S.F., et al. (2015). “Society for Endocrinology UK consensus statement on the man- agement of disorders of sex development.” Journal of Pediatric Endocrinology and Metabolism.
Lanciotti, L., et al. (2019). “Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS).” International Journal of Environmental Research and Public Health.
Jafarli, I., John, B., Syed, M., & Huseynova, I. (2025). “Androgen receptors and keloid treat- ment in children: insights on androgen insensitivity syndrome.” Journal of Neonatal Surgery, 14, 1099–1105.
Oladipo, F.T., Jafarli, I., Huseynova, İ., & Reynolds, H.E. (2025). “Androgen receptor expres- sion in the foreskin of children born with hypospadias: a systematic review.” Pediatric Surgery International, 41(1), 301.
Tarulli GA, et al. Spatiotemporal map of key signaling factors during early penis development. Dev Dyn. 2021;251(4):609-24.
Pakula H, et al. A Tale of Two Signals: AR and WNT in Development and Tumorigenesis. Cancers (Basel). 2017;9(2):14.
Lin C, et al. Temporal and spatial dissection of Shh signaling in genital tubercle development. Development. 2009;136(23):3959-67.
Elmelund E. Androgen receptor antagonist flutamide modulates estrogen receptor alpha ex- pression. Front Endocrinol. 2025;16:1654965.
Chang C, et al. AR Physiological Roles in Male and Female Reproductive Systems. Biol Re- prod. 2013;89(6):134.
Lin CC, et al. Androgen receptor as a regulator of ZEB2 expression. Endocr Relat Cancer. 2014;21(3):473-83.
Baskin LS. Hypospadias and urethral development. J Urol. 2000;163(3):951-6.
Karseladze AI, et al. AIS with Bilateral Gonadal Sertoli Cell Lesions. J Clin Med. 2024;13(4):929.
Ko S. Unraveling the Androgen Receptor’s Role in Hypospadias. Int J Mol Sci. 2024;25(19):10644.
