Abstract
Complete androgen insensitivity syndrome (CAIS) associated with Müllerian remnant is rare during childhood. The Müllerian system usually regresses because of the presence of the anti-Müllerian hormone (AMH) originating from the Sertoli cells of the gonads. Rarely, residual Müllerian structures may exist. We present two cases from the same family, raised as females. They were 12 and 18 years old, respectively, and they had Tanner V breast development but Tanner I-II pubic hair. The older patient had primary amenorrhea. Both have a 46,XY genotype. Pelvic ultrasonography revealed no uterus and ovaries. The patients underwent bilateral laporoscopic gonadectomy. Both had residual Müllerian structures. Mutation analyses were performed, and both patients were found to be carrying a point mutation in exon 4 of the AR gene consisting of a G nucleotide deletion at position c.1890delG, followed by a frame-shift mutation and a stop codon. This mutation has not been described yet in the literature. Although the association with CAIS and Müllerian remnant is rare, no genetic defect specific to androgen insensitivity with Müllerian remnants has been identified so far.
Author contribution:
Ayla Güven, Diagnosis, therapy and follow-up of cases, editing of the manuscript. Fatma Dursun, Writing of the manuscript. Seyma Özkanlı, Pathologic examination of case 2. Berrin Güçlüer, Pathologic examination of case 1. L. İhsan Kuru, Radiologic examination of cases.
We would like to thank Prof. Laura Audi from Hospital Vall d’Hebron, Pediatric Endocrinology Unit for molecular genetics analyses. We also thank Associate Prof. Dr Cigdem Ulukaya Durakbasa from Medeniyet University Medical Faculty Department of Pediatric Surgery for the laparoscopic operation.
Conflict of interest statement
Authors’ conflict of interest disclosure:None of the authors has personal or financial conflict of interests.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
References
1. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, et al. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 1995;16:271–321.10.1210/edrv-16-3-271Search in Google Scholar
2. Michala L, Creighton SM. The XY female. Best Pract Res Clin Obstet Gynaecol 2010;24:139–48.10.1016/j.bpobgyn.2009.09.009Search in Google Scholar
3. Oka M, Katabuchi H, Munemura M, Mizumoto J, Maeyama M. An unusual case of male pseudohermaphroditism: complete testicular feminization associated with incomplete differentiation of the Müllerian duct. Fertil Steril 1984;41:154–6.10.1016/S0015-0282(16)47559-XSearch in Google Scholar
4. Dodge ST, Finkelston MS, Miyazawa K. Testicular feminization with incomplete Müllerian regression. Fertil Steril 1985;43:937–8.10.1016/S0015-0282(16)48626-7Search in Google Scholar
5. Ulloa-Aguirre A, Mendez JP, Angeles A, Fernandez del Castilo C, Chavez B, et al. The presence of müllerian remnants in the complete androgen insensitivity syndrome: a steroid hormone-mediated defect? Fertil Steril 1986;45:302–5.10.1016/S0015-0282(16)49173-9Search in Google Scholar
6. Damiani D, Mascolli MA, Almeida MJ, Jaubert F, Fellous M, et al. Persistence of Müllerian remnants in complete androgen insensitivity syndrome. J Ped Endocrinol Metabol 2002;15:1553–6.10.1515/JPEM.2002.15.9.1553Search in Google Scholar PubMed
7. Menakaya UA, Aligbe J, Iribhogbe P, Agoreyo F, Okonofua FE. Complete androgen insensitivity syndrome with persistent Müllerian derivatives: a case report. J Obstet Gynaecol 2005;25:403–5.10.1080/01443610500143226Search in Google Scholar PubMed
8. Van YH, Lin JL, Huang SF, Luo CC, Hwang CS, et al. Novel point mutations in complete androgen insensitivity syndrome with incomplete Müllerian regression: two Taiwanese patients. Eur J Pediatr 2003;162:781–4.10.1007/s00431-003-1301-0Search in Google Scholar PubMed
9. Sultan CH, Gobinet J, Terouanne B, Paris F, Belon CH, et al. The androgen receptor: molecular pathology. J Soc Biol 2002;196:223–40.10.1051/jbio/2002196030223Search in Google Scholar
10. Nichols JL, Bieber EJ, Gell JS. Case of sisters with complete androgen insensitivity syndrome and discordant Müllerian remnants. Fertil Steril 2009;91:932.e15–8.10.1016/j.fertnstert.2008.09.027Search in Google Scholar PubMed
11. Hiort O, Sinnecker GH, Holterhus PM, Nitsche EM, Kruse K. The clinical molecular spectrum of androgen insensitivity syndromes. Am J Med Genet 1996;63:218–22.10.1002/(SICI)1096-8628(19960503)63:1<218::AID-AJMG38>3.0.CO;2-PSearch in Google Scholar
12. Nitsche EM, Hiort O. The molecular basis of androgen insensitivity. Horm Res 2000;54:327–33.Search in Google Scholar
13. 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 müllerian structures, and germ cell tumors in dysgenetic gonads. Fertil Steril 1999;72:170–3.10.1016/S0015-0282(99)00169-7Search in Google Scholar
14. Philibert P, Audran F, Pienkowski C, Morange I, Kohler B, et al. Complete androgen insensitivity syndrome is frequently due to premature stop codons in exon 1 of the androgen receptor gene: an international collaborative report of 13 new mutations. Fertil Steril 2010;94:472–6.10.1016/j.fertnstert.2009.03.057Search in Google Scholar
15. Boehmer AL, Brinkmann O, Brüggenwirth H, van Assendelft C, Otten BJ, et al. Genotype versus phenotype in families with androgen insensitivity syndrome. J Clin Endocrinol Metabol 2001;86:4151–60.10.1210/jcem.86.9.7825Search in Google Scholar
16. Corbetta S, Muzza M, Avagliano L, Bulfamante G, Gaetti L, et al. Gonadal structures in a fetus with complete androgen insensitivity syndrome and persistent Müllerian derivatives: comparison with normal fetal development. Fertil Steril 2011;95:e9–14.10.1016/j.fertnstert.2010.09.028Search in Google Scholar
17. Audi L, Fernández-Cancio M, Carrascosa A, Andaluz P, Torán N, et al. Grupo de Apoyo al Síndrome de Insensibilidad a los Andrógenos (GrApSIA). Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46, XY disorder of sex development. J Clin Endocrinol Metabol 2010;95:1876–88.10.1210/jc.2009-2146Search in Google Scholar
18. Rey R, Mebarki F, Forest MG, Mowszowicz I, Cate RL, et al. Anti-Müllerian hormone in children with androgen insensitivity. J Clin Endocrinol Metabol 1994;79:960–4.Search in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
