Persistent Mullerian duct syndrome in Schnauzer Miniature

Persistent Mullerian duct syndrome (PMDS) is a disorder of sexual development that affects males. Males with this disorder also develop a part of female reproductive organs. The affected males can also have a uterus, oviducts, ectocervix and a part of vagina that extends to the prostate gland. This anomaly results in unilateral or bilateral cryptorchidism (undescended testis into the scrotum) and its consequences such as infertility and an increased risk for testicular cancer.  This condition is often accompanied with inflammation, e.g., pyometra (infection in the uterus) and associated effects – polydipsia, polyuria, and loss of appetite.

During the normal foetal development, the Anti-Mullerian hormone (AMH) and its receptor (AMHR2) induces the regression of the Mullerian duct. This autosomal recessive nonsense mutation, specifically substitution C to T (c.241C> T; p.R81 *) in AMHR2 has been identified in Miniature Schnauzers. It is not known yet whether this mutation occurs in other breeds. This mutation causes that AMHR2 is not expressed and the regression of Mullerian duct fails during embryonal development in affected males. Females with this mutation develop normal female genitals.

The inheritance pattern of this disease is autosomal recessive. The disease occurs in recessive homozygous males that inherited the mutant allele from both parents. This disease does not develop in recessive homozygous females, who, however, carry over the mutant allele to its offspring. A heterozygote that inherited the mutant allele only from one parent has no symptoms and is clinically healthy, however can pass the mutated allele to its offspring.

As there are hidden carriers of this mutation in the population, genetic tests are recommended that can determine the genotype of an animal and help prevent spreading of this disease.

.

References:

Pujar, S., Meyers-Wallen, VN.: A molecular diagnostic test for persistent Müllerian duct syndrome in miniature schnauzer dogs. Sex Dev 3:326-8, 2009. Pubmed reference: 20051676.

Smit, M.M., Ekenstedt, K.J., Minor, K.M., Lim, C.K., Leegwater, P., Furrow, E.: Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome. Reprod Domest Anim 53:371-376, 2018. Pubmed reference: 29194807.