Testicular Feminization or Androgen Insensitivity Syndrome (AIS) in Iran: a Retrospective Analysis of 30-Year Data
Background: Androgen insensitivity syndrome (AIS) or testicular feminization is a partial or complete inability of cell response to androgen. The cause is enzymatic defect in synthesis of testosterone, resulting sexually immature phenotypically female, with primary amenorrhea. There are three categories of AIS, complete, partial and mild, depending on the degree of external genital masculinization. The aim of this study was to find out chromosomal abnormalities, and correlation between AIS and maternal/paternal age, parents' consanguineous marriage, family history and clinical observation, in Iranian AIS patients.
Method: This study includes a retrospective data analysis of 72,000 families' medical records in the Genetic Clinic in Tehran, during a 30-yr period (1984-2014). The essential basis for the patients' referral to the clinic by gynecologists was primary amenorrhea. Cytogenetic abnormalities has been confirmed by chromosome G-banding and conventional staining methods.
Results: Seventy AIS female patients with 46XY pattern were cytogenetically diagnosed and the frequency of AIS syndrome was estimated about 0.05% (~70/140000). The results showed no association between AIS and maternal or paternal age nor were the marital pattern of the parents. The clinical findings illustrated that primary amenorrhea had the highest indication for referral of AIS patients for genetic counseling and cytogenetic study.
Conclusion: No correlation was observed between AIS and maternal or paternal age or consanguineous marriages. Amenorrhea is the most clinically observed sign of AIS patients.
Morris JM (1953). The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol, 65:1192-1211.
Galani A, Kitsiou-Tzeli S, Sofokleous C, Kanavakis E, Kalpini-Mavrou A (2008). Androgen insensitivity syndrome: clinical features and molecular defects. Hormones (Athens), 7:217-29.
Mendoza N, Motos MA (2013). Androgen insensitivity syndrome. Gynecol Endocrinol, 29:1-5.
Stouffs K, Tournaye H, Liebaers I, Lissens W (2009). Male infertility and the involvement of the X chromosome. Hum Reprod Update, 15:623-37.
Gottlieb B, Beitel LK, Trifiro MA (2014). Androgen Insensitivity Syndrome. Initial Posting: March 24, 1999; Last Update: July 10, 2014. http://www.ncbi.nlm.nih.gov/books/NBK1429/
Boehmer AL, Brinkmann O, Bruggenwirth H et al. (2001). Genotype versus phenotype in families with androgen insensitivity syndrome. J Clin Endocrinol Metab, 86:4151-60.
Mazen I, El-Ruby M, Kamal R, El-Nekhely I, El-Ghandour M, Tantawy S, El-Gammal M (2010). Screening of genital anomalies in newborns and infants in two egyptian governorates. Horm Res Paediatr, 73:438-42.
Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J (2012). Androgen insensitivity syndrome. Lancet, 380:1419-28.
Hughes IA, Deeb A (2006). Androgen resistance. Best Pract Res Clin Endocrinol Metab, 20:577-98.
Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS (1995). Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev, 16:271-321.
Pizzo A, Lagana AS, Borrielli I, Dugo N (2013). Complete androgen insensitivity syndrome: a rare case of disorder of sex development. Case Rep Obstet Gynecol, 2013:232696.
Ferlin A, Vinanzi C, Garolla A, Selice R, Zuccarello D, Cazzadore C, Foresta C (2006). Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin Endocrinol (Oxf), 65:606-10.
Zuccarello D, Ferlin A, Vinanzi C, Prana E, Garolla A, Callewaert L, Claessens F, Brinkmann AO, Foresta C (2008). Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. Clin Endocrinol (Oxf), 68:580-8.
Migeon BR, Brown TR, Axelman J, Migeon CJ (1981). Studies of the locus for androgen receptor: localization on the human X chromosome and evidence for homology with the Tfm locus in the mouse. Proc Natl Acad Sci U S A, 78:6339-43.
Hiort O (2013). Clinical and molecular aspects of androgen insensitivity. Endocr Dev, 24:33-40.
Hughes IA, Werner R, Bunch T, Hiort O (2012). Androgen insensitivity syndrome. Semin Reprod Med, 30:432-42.
Tadokoro-Cuccaro R, Hughes IA (2014). Androgen insensitivity syndrome. Curr Opin Endocrinol Diabetes Obes, 21:499-503.
Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010). Molecular cell biology of androgen receptor signalling. Int J Biochem Cell Biol, 42:813-27.
Brinkmann AO (2011). Molecular mechanisms of androgen action--a historical perspective. Methods Mol Biol, 776:3-24.
Chang C, Yeh S, Lee SO, Chang TM (2013). Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells. Nucl Recept Signal, 11:e001.
Asl Zare M, Kalantari MR, Asadpour AA, Kamalati A (2014). Bilateral laparoscopic gonadectomy in a patient with complete androgen insensitivity syndrome and bilateral sertoli-leydig cell tumor: a case report and brief review of the literature. Nephrourol Mon, 6:e15278.
Iwamoto I, Yanazume S, Fujino T, Yoshioka T, Douchi T (2005). Leydig cell tumor in an elderly patient with complete androgen insensitivity syndrome. Gynecol Oncol, 96:870-2.
Rutgers JL, Scully RE (1991). The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases. Int J Gynecol Pathol, 10:126-44.
Wysocka B, Serkies K, Debniak J, Jassem J, Limon J (1999). Sertoli cell tumor in androgen insensitivity syndrome--a case report. Gynecol Oncol, 75:480-3.
Farhud DD, Mahmoudi M, Kamali MS, Marzban M, Andonian LRS (1991). Consanguinity in Iran. Iran J Public Health, 20:1-13.
Leow MK, Loh KC (2001). 46, XY female--a case report. Ann Acad Med Singapore, 30:71-5.
Starzyk J, Gorska A, Janus D (2005). [Complete androgen insensitivity syndrome in 16-year-old girl with female phenotype]. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw, 11:47-9.
Scott EC, Greenberg TS, Arndt S, Ramsay M, Shires R (2006). Complete androgen insensitivity syndrome in a black South African family: a clinical and molecular investigation. Endocr Pract, 12:664-9.
Jarzabek K, Philibert P, Koda M, Sulkowski S, Kotula-Balak M, Bilinska B, Kottler ML, Wolczynski S, Sultan C (2007). Primary amenorrhea in a young Polish woman with complete androgen insensitivity syndrome and Sertoli-Leydig cell tumor: identification of a new androgen receptor gene mutation and evidence of aromatase hyperactivity and apoptosis dysregulation within the tumor. Gynecol Endocrinol, 23:499-504.
Subramaniam A, Singh R, Tilak P, Devi R, Kulandaivelu M, Kumarasamy T (2013). Androgen insensitivity syndrome: ten years of our experience. Front Biosci (Elite Ed), 5:779-84.
|Issue||Vol 45 No 1 (2016)|
|Androgen insensitivity syndrome (AIS) Testicular feminization Human androgen receptor (HAR) Amenorrhea Iran|
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