FaCD Online Syndrome Fact Sheet

Last updated: 15 May 2009

Name: Androgen Insensitivity Syndrome

Synonym: CAIS, Testicular Feminisation, AIS, Morris syndrome; incl. Reifenstein Syndrome

Mode of Inheritance: X-linked

OMIM number: 300068   312300  


AR, mapped to Xq11-q12

Tumor features

breast cancer, male
testicular gonadoblastoma
testicular hamartoma
testicular Sertoli-Leydig cell tumor

Tumor features (possible)

leukemia, acute myeloid (AML, incl. ANLL)
myelodysplastic syndrome (MDS)

Non-tumor features

male (46,XY) pseudohermaphroditism


Mutations in the androgen receptor coding gene on the X chromosome cause pseudo-hermaphroditism in the XY individual through androgen insensitivity. External genitals in patients with the complete androgen receptor insensitivity syndrome (CAIS) are female. The gonads are undescended testes, located intra-abdominally, inguinally, or in the labia. Mullerian structures, including uterus, are absent, because of the AMH production by the testes.[1]

Sex cord hamartomas and Sertoli cell adenomas are common findings in CAIS, with a prevalence of 63% and 23%, respectively, observed in one series of 43 patients[2]. Patients with AIS show an increased frequency of testicular malignancies with risks estimated between 2 and 33%, 2-5/10 % might be the most realistic estimate. Seminoma[3-8] and sex-cord stromal tumors (particularly Sertoli-cell tumors)[9-14] are the most common tumor types observed. Intra-tubular germ cell tumors have been observed in rare cases[18]. Gonadoblastoma[15], Yolk sac tumor[16], embryonal carcinoma[17]) and Leydig cell tumors[19] have been reported as well. A patient with MDS/AML has been published[22].

Partial androgen insensitivity (Reifenstein syndrome) and, more general, variants of the androgen receptor gene appear to be associated with increased male breast cancer risk[20,21].


Androgen Insensitivity Syndrome Support Group (AISSG) 18 1 08


[1] Loy CJ, Yong EL. Sex, infertility and the molecular biology of the androgen receptor. Current Opinion in Obstetrics and Gynecology 2001; 13(3):315-321.
[2] Rutgers JL, Scully RE. The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases. Int J Gynecol Pathol 1991; 10(2):126-144.
[3] Kocak M, Yalvac S, Pata O, Turan H, Haberal A. A seminoma case which occurred in a patient with familial testicular feminization syndrome. Acta Obstet Gynecol Scand 2000; 79(10):890-891.
[4] Sakai N, Yamada T, Asao T, Baba M, Yoshida M, Murayama T. Bilateral testicular tumors in androgen insensitivity syndrome. Int J Urol 2000; 7(10):390-392.
[5] Chan LY, Wong SF, Yu VS. Advanced stage of dysgerminoma in testicular feminisation: is radical surgery necessary? Aust N Z J Obstet Gynaecol 2000; 40(2):224-225.
[6] Collins GM, Kim DU, Logrono R, Rickert RR, Zablow A, Breen JL. Pure seminoma arising in androgen insensitivity syndrome (testicular feminization syndrome): a case report and review of the literature. Mod Pathol 1993; 6(1):89-93.
[7] Hurt WG, Bodurtha JN, McCall JB, Ali MM. Seminoma in pubertal patient with androgen insensitivity syndrome. Am J Obstet Gynecol 1989; 161(3):530-531.
[8] Horcher E, Grunberger W, Parschalk O. Classical seminoma in a case of testicular feminization syndrome. Prog Pediatr Surg 1983; 16:139-41.:139-141.
[9] Hawkyard S, Poon P, Morgan DR. Sertoli tumour presenting with stress incontinence in a patient with testicular feminization. BJU Int 1999; 84(3):382-383.
[10] Knoke I, Jakubiczka S, Ottersen T, Goppinger A, Wieacker P. A(870)E mutation of the androgen receptor gene in a patient with complete androgen insensitivity syndrome and Sertoli cell tumor. Cancer Genet Cytogenet 1997; 98(2):139-141.
[11] Fleckenstein GH, Gunawan B, Brinck U, Wuttke W, Emons G. Simultaneous sertoli cell tumor and adenocarcinoma of the tunica vaginalis testis in a patient with testicular feminization. Gynecol Oncol 2002; 84(3):460-463.
[12] Wysocka B, Serkies K, Debniak J, Jassem J, Limon J. Sertoli cell tumor in androgen insensitivity syndrome--a case report. Gynecol Oncol 1999; 75(3):480-483.
[13] Damjanov I, Nesbitt KA, Reardon MP, Vidone RA. Giant sertoli cell adenoma in testicular feminization syndrome. Obstet Gynecol 1976; 48(5):624-627.
[14] McNeill SA, O'Donnell M, Donat R, Lessells A, Hargreave TB. Estrogen secretion from a malignant sex cord stromal tumor in a patient with complete androgen insensitivity. Am J Obstet Gynecol 1997; 177(6):1541-1542.
[15] Chen CP, Chen SR, Wang TY, Wang W, Hwu YM. A frame shift mutation in the DNA-binding domain of the androgen receptor gene associated with complete androgen insensitivity, persistent mullerian structures, and germ cell tumors in dysgenetic gonads. Fertil Steril 1999; 72(1):170-173.
[16] Handa N, Nagasaki A, Tsunoda M, Ohgami H, Kawanami T, Sueishi K, Nagoshi M. Yolk sac tumor in a case of testicular feminization syndrome. J Pediatr Surg 1995; 30(9):1366-1367.
[17] Lecca U, Parodo G, Fiore R, Martino E. Embryonal carcinoma in two cases of androgen insensitivity syndrome: clinical, endocrinological and pathological features. Eur J Gynaecol Oncol 1988; 9(6):489-496.
[18] Casellato S, Gazzano G, Musi G, Spinelli M, Carmignani L, Rocco F. First case of bilateral intratubular germ cell tumor in androgen insensivity syndrome. Archivio italiano di urologia, andrologia 2007; 79(3):135-7.
[19] Iwamoto I, Yanazume S, Fujino T, Yoshioka T, Douchi T. Leydig cell tumor in an elderly patient with complete androgen insensitivity syndrome. Gynecologic oncology 2005; 96(3):870-2.
[20] MacLean HE, Brown RW, Beilin J, Warne GL, Zajac JD. Increased frequency of long androgen receptor CAG repeats in male breast cancers. Breast cancer research and treatment 2004; 88(3):239-46.
[21] Wooster R, Mangion J, Eeles R, Smith S, Dowsett M, Averill D, Barrett-Lee P, Easton DF, Ponder BA, Stratton MR. A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nature genetics 1992; 2(2):132-4.
[22] Olshanskayaa YV, Udovichenkoa AI, Kolosovaa LY, Kokhnoa AV. Myelodysplastic syndrome with monosomy 7 in a patient with XY gonadal dysgenesis (incomplete testicular feminization). Cancer Genetics and Cytogenetics, 2009;191:113-114