Persistent Müllerian Duct Syndrome, PMDS

Gene: AMHR2

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, AMHR2 gene; c.238 C>T, p.(R88 STOP), exon3

Medical system: Reproductive

Breeds: American Staffordshire Terrier/Amstaff, Chihuahua, Pembroke Welsh Corgi, Schnauzer - Miniature, Scottish Terrier, Yorkshire Terrier

Age of onset of clinical signs:

Persistent Müllerian duct is a developmental disease of the reproductive system that affects male dogs. All fetuses (male, female) possess structures called the Müllerian ducts, which are the precursors of the uterus, uterine horns and the cranial part of the vagina. In the female fetus, the Müllerian ducts are retained. In a normal male fetus, the Müllerian ducts regress. In a male fetus with a double mutation in the AMHR2 gene, the Müllerian ducts do not regress, resulting in an adult male with remnants of female reproductive organs. In half of these cases, the dog is fertile, as it has normal testicles. In the other half of cases, the animal is infertile and often suffers from cryptorchidism, i.e. the testicles have not fully descended into the scrotum. This cryptorchid condition predisposes the dog to testicular tumours.

References:

OMIA link: [2775-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Szabo Z, Moser J, Vincenti S. (2023) Persistent mullerian duct syndrome in a dog. Schweiz Arch Tierheilkd 165:189-0.  [pubmed/36852872]

Dzimira S, Wydooghe E, Van Soom A, Van Brantegem L, et al. (2018) Sertoli Cell Tumour and Uterine Leiomyoma in Miniature Schnauzer Dogs With Persistent Müllerian Duct Syndrome Caused by Mutation in the AMHR2 Gene.  J Comp Pathol. 161:20-24. [pubmed/30173854]

Smit MM, Ekenstedt KJ, Minor KM, et al. (2018) Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome.  Reprod Domest Anim. 53(2):371-376. [pubmed/29194807]

Park EJ, Lee S-H, Jo Y-K, et al. (2017) Coincidence of persistent Müllerian duct syndrome and testicular tumors in dogs.  BMC Vet Res 13:156. [pubmed/28576146]

Wu X, Wan S, Pujar S, et al. (2009) A single base pair mutation encoding a premature stop codon in the MIS type II receptor is responsible for canine persistent Müllerian duct syndrome. J Androl. 30(1):46-56. [pubmed/18723470]