Familial case of late diagnosis of Persistence of Müllerian derivatives syndrome type 1

Persistent müllerian duct syndrome (PMDS) is a rare variant of the disorder of sex development (DSD) 46,XY characterized by the presence of Müllerian duct derivatives in 46,XY males. Since cryptorchidism is the only external manifestation of PMDS, until recently, PMDS was not diagnosed in patients and detection of Müllerian duct derivatives during the surgical treatment of cryptorchidism in patients with 46,XY karyotype was regarded as a variant of gonadal dysgenesis, leading to an erroneous choice of treatment strategy in these patients. Only the development of the molecular diagnostics methods, in particular, new generation sequencing, which enable simultaneous investigation of several candidate genes, provided accurate differential diagnosis of the PMDS. This article reports a clinical case of late diagnosis of the familial form of PMDS caused by mutation in the AMH gene. Detected persistent Müllerian derivatives in combination with agenesis of the testicle in the proband at an early age led to the diagnosis gonadal dysgenesis. Given the proven high risk of malignization of the gonads located outside the scrotum in patients with gonadal dysgenesis, the patient underwent removal of the only gonad located in the inguinal canal. The correct diagnosis was established after a comprehensive molecular genetic study using a new generation sequencing with the «disorders of sex development» panel. This study detected a homozygous mutation in the AMH gene.

1. Knebelmann B, Boussin L, Guerrier D, et al. Anti-mullerian hormone Bruxelles: a nonsense mutation associated with the persistent mullerian duct syndrome. PNAS. 1991;88(9):3767-3771. doi: 10.1073/pnas.88.9.3767

2. Barthold JS, Gonzalez R. The epidemiology of congenital cryptorchidism, testicular ascent and orchiopexy. J Urol. 2003;170 (6 Pt 1):2396-2401. doi: 10.1097/01.ju.0000095793.04232.d8

3. Brandli DW, Akbal C, Eugsster E, et al. Persistent mullerian duct syndrome with bilateral abdominal testis: surgical approach and review of the literature. J Pediatr Urol. 2005;1(6):423-427. doi: 10.1016/j.jpurol.2005.03.011

4. Naouar S, Maazoun K, Sahnoun L, et al. Transverse testicular ectopia: a three-case report and review of the literature. Urology. 2008;71(6):1070-1073. doi: 10.1016/j.urology.2007.11.133

5. Wuerstle M, Lesser T, Hurwitz R, et al. Persistent mullerian duct syndrome and transverse testicular ectopia: embryology, presentation, and management. J Pediatr Surg. 2007;42(12):2116-2119. doi: 10.1016/j.jpedsurg.2007.09.003

6. Zhapa E, Castagnetti M, Alaggio R, et al. Testicular fusion in a patient with transverse testicular ectopia and persistent mullerian duct syndrome. Urology. 2010;76(1):62-64. doi: 10.1016/j.urology.2009.10.032

7. Yu TJ. The character of variant persistent mullerian-duct structures. Pediatr Surg Int. 2002;18(5-6):455-458. doi: 10.1007/s00383-002-0718-2

8. Marcus KA, Halbertsma FJ, Picard JY, Otten BJ. A visual pitfall: persistent mullerian duct syndrome (PMDS). Acta Paediatr. 2008;97(1):129-132. doi: 10.1111/j.1651-2227.2007.00573.x

9. Imbeaud S, Faure E, Lamarre I, et al. Insensitivity to anti-mullerian hormone due to a mutation in the human anti-mullerian hormone receptor. Nat Genet. 1995;11(4):382-388. doi: 10.1038/ng1295-382

10. De Santa Barbara P, Bonneaud N, Boizet B, et al. Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-mullerian hormone gene. Mol Cell Biol. 1998;18(11):6653-6665. doi: 10.1128/MCB.18.11.6653

11. Arango NA, Lovell-Badge R, Behringer RR. Targeted mutagenesis of the endogenous mouse mis gene promoter. Cell. 1999;99(4):409-419. doi: 10.1016/s0092-8674(00)81527-5

12. Von Seemen H. Pseudohermaphroditismus masculinus internus-kryptochismus-Hernia inguinalis congenita. Bruns’ Beitr Klin Chir. 1927;141:370-379.

13. Miller A, Hong MKH, Hutson JM. The broad ligament: a review of its anatomy and development in different species and hormonal environments. Clin Anat. 2004;17(3):244-251. doi: 10.1002/ca.10173

14. di Clemente N, Wilson C, Faure E, et al. Cloning, expression, and alternative splicing of the receptor for anti-müllerian hormone. Mol Endocrinol. 1994;8(8):1006-1020. doi: 10.1210/mend.8.8.7997230

15. Меновщикова Л.Б., Калинченко Н.Ю., Тюльпаков А.Н., и др. Синдром персистенции мюллеровых протоков у мальчика с синдромом непальпируемых яичек с двух сторон // Детская хирургия. — 2016. — Т. 20. — №5. — С. 274—276. [Menovshchikova LB, Kalinchenko NY, Tyulpakov AN, et al. Persistent mullerian duct syndrome in a boy with bilateral non-palpable testes. Pediatric surgery. 2016;20(5):274-276. (In Russ.)]. doi: 10.18821/1560-9510-2016-20-5-274-276