OMIA 000791-9615 : Persistent Mullerian duct syndrome in Canis lupus familiaris

In other species: domestic cat , goat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 235255 , 261550

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2009

Species-specific name: Persistent Mullerian Duct Syndrome

Species-specific symbol: PMDS

Species-specific description: PMDS is a type of XY disorder of sexual development (XY DSD), characterized by the presence of Müllerian duct derivatives in otherwise normal males. The mode of inheritance for the PMDS trait in miniature schnauzers is sex-limited autosomal recessive. Affected dogs are 78,XY and have bilateral testes. Both affected and carrier males appear externally normal, although approximately 50% of affected dogs are unilaterally or bilaterally cryptorchid. Common sequelae are Sertoli cell tumors in cryptorchid PMDS males and pyometra. Treatment in affected dogs is gonadectomy and hysterectomy. Testing for the mutation prior to breeding is recommended, because affected dogs with scrotal testes are fertile and carriers have no clinical signs.

Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Inheritance: The mode of inheritance is sex-limited autosomal recessive, and both affected and carrier dogs are karyotypically normal [Wu et al., 2009].

Affected males are homozygous and will pass the mutation to all of their offspring.

Carrier (heterozygous) males will pass the mutation to half their offspring, on average.

Females are not affected, but can be either homozygous or heterozygous for the mutation.

Homozygous carrier females will pass the mutation to all of their offspring and heterozygous carrier females will pass the mutation to half their offspring, on average.

Molecular basis: The causative mutation of PMDS in the miniature schnauzer is a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor gene (AMHR2, Wu et al., 2009).

Clinical features: Homozygous affected males have normal male external genitalia, except that approximately 50% are unilaterally or bilaterally cryptorchid.

PMDS males having at least one descended testicle can be fertile. Carrier males and carrier females are reproductively normal.

PMDS dogs may present at any age as a dog with normal male external genitalia or a cryptorchid dog. If cryptorchid, they may present as an adult with signs of testicular tumor. As pyometra can be a sequelae, affected dogs may present with typical signs,such as polydipsia, polyuria and inappetance.

Pathology: During development of the male reproductive tract, Müllerian inhibiting substance (MIS), also known as Anti Mullerian hormone (AMh), causes regression of Mullerian duct precursors in males. MIS binding to its type II receptor (AMhR2) in the target organs is necessary to induce regression. If MIS signaling is faulty, the Müllerian ducts fail to regress in males, causing PMDS [Wu et al., 2009]. In addition to having male internal genitalia, PMDS males have bilateral oviducts, a complete uterus , a cervix, and the cranial part of the vagina, which ends in the dorsal prostate. There is a firm attachment between each cranial tip of the uterine horn and the caudal pole of the testis, which likely hinders testicular descent [Wu et al., 2009]. Some common complications are Sertoli cell tumors in cryptorchid PMDS dogs and pyometra. Pyometra may be facilitated by the narrow connection between the cranial vagina and the prostatic urethra, which allows pathogens to ascend to the uterus, but impedes purulent drainage [Wu et al., 2009]. On histologic section, cryptorchid testes from PMDS dogs lack germ cells, though scrotal testes appear normal.

Prevalence: The prevalence is unknown, although the causative mutation seems to be widely distributed in the breed with cases in the USA, Europe and Japan [Meyers-Wallen, 2011].

Control: To prevent PMDS, affected dogs should not be bred and carriers should not be bred to carriers. To reduce the frequency of the mutation in the miniature schnauzer breed, carriers should be removed from the breeding population. Because affected and carrier miniature schnauzers can have normal male external genitalia, testing for the mutation prior to breeding is recommended. As carrier females have no signs and are reproductively normal, testing for the mutation prior to breeding is recommended.

Genetic testing: The causative mutation of PMDS in the miniature schnauzer is a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor gene (AMHR2, Wu et al., 2009). A DNA test for this mutation can identify affected, carrier and normal miniature schnauzers (Pujar et al 2009). This is

a PCR test followed by digestion of the PCR product by a restriction enzyme.

Breeds: Basset Hound, Miniature Schnauzer.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
AMHR2 anti-Mullerian hormone receptor, type II Canis lupus familiaris 27 NC_006609.3 (1795601..1788420) AMHR2 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Miniature Schnauzer Persistent Mullerian duct syndrome AMHR2 nonsense (stop-gain) c.241C>T p.R??* 2009 18723470

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 De Lorenzi, L., Arrighi, S., Groppetti, D., Bonacina, S., Parma, P. :
Persistent Müllerian Duct Syndrome in a German Shepherd Dog. Sex Dev :, 2018. Pubmed reference: 30086548. DOI: 10.1159/000492037.
2012 Meyers-Wallen, V.N. :
Gonadal and sex differentiation abnormalities of dogs and cats. Sex Dev 6:46-60, 2012. Pubmed reference: 22005097. DOI: 10.1159/000332740.
2011 Breshears, M.A., Peters, J.L. :
Ambiguous genitalia in a fertile, unilaterally cryptorchid male miniature schnauzer dog. Vet Pathol 48:1038-40, 2011. Pubmed reference: 21248100. DOI: 10.1177/0300985810396104.
2010 Vegter, A.R., Kooistra, H.S., van Sluijs, F.J., van Bruggen, L.W., Ijzer, J., Zijlstra, C., Okkens, A.C. :
Persistent Mullerian duct syndrome in a Miniature Schnauzer dog with signs of feminization and a Sertoli cell tumour. Reprod Domest Anim 45:447-52, 2010. Pubmed reference: 18954385. DOI: 10.1111/j.1439-0531.2008.01223.x.
2009 Matsuu, A., Hashizume, T., Kanda, T., Nagano, M., Sugiyama, A., Okamoto, Y., Hikasa, Y. :
A case of persistent Müllerian duct syndrome with sertoli cell tumor and hydrometra in a dog J Vet Med Sci 71:379-81, 2009. Pubmed reference: 19346713.
Meyers-Wallen, VN. :
Review and update: genomic and molecular advances in sex determination and differentiation in small animals. Reprod Domest Anim 44 Suppl 2:40-6, 2009. Pubmed reference: 19754534. DOI: 10.1111/j.1439-0531.2009.01433.x.
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. DOI: 10.1159/000273264.
Whyte, A., Monteagudo, L.V., Díaz-Otero, A., Lebrero, M.E., Tejedor, M.T., Falceto, M.V., Whyte, J., Gallego, M. :
Malformations of the epididymis, incomplete regression of the mesonephric tubules and hyperplasia of Leydig cells in canine persistence of Müllerian duct syndrome. Anim Reprod Sci 115:328-33, 2009. Pubmed reference: 19097712. DOI: 10.1016/j.anireprosci.2008.11.008.
Wu, X., Wan, S., Pujar, S., Haskins, ME., Schlafer, DH., Lee, MM., Meyers-Wallen, VN. :
A Single Base Pair Mutation Encoding a Premature Stop Codon in the MIS type II receptor is Responsible for Canine Persistent Mullerian Duct Syndrome. J Androl 30:46-56, 2009. Pubmed reference: 18723470. DOI: 10.2164/jandrol.108.005736.
2004 Kuiper, H., Distl, O. :
[Intersexuality in dogs: causes and genetics] Dtsch Tierarztl Wochenschr 111:251-8, 2004. Pubmed reference: 15287579.
Kuiper, H., Wagner, F., Drögemüller, C., Distl, O. :
Persistent Mullerian duct syndrome causing male pseudohermaphroditism in a mixed-breed dog. Vet Rec 155:400-1, 2004. Pubmed reference: 15499815.
1996 Jonen, H., Nickel, R.F. :
The persistant Mullerian duct syndrome - a hereditary type of male pseudohermaphroditism in a Bassethound [German] Kleintierpraxis 41:911 ff., 1996.
1993 Meyers-Wallen, V.N. :
Genetics of Sexual Differentiation and Anomalies in Dogs and Cats Journal of Reproduction and Fertility :441-452, 1993. Pubmed reference: 8229960.
Meyers-Wallen, V.N., Lee, M.M., Manganaro, T.F., Kuroda, T., Maclaughlin, D., Donahoe, P.K. :
Mullerian Inhibiting Substance Is Present in Embryonic Testes of Dogs with Persistent Mullerian Duct Syndrome Biology of Reproduction 48:1410-1418, 1993. Pubmed reference: 8318594.
1992 Nickel, R.F., Ubbink, G., Vandergaag, I., Vansluijs, F.J. :
Persistent Mullerian Duct Syndrome in the Basset Hound Tijdschrift Voor Diergeneeskunde 117:S31, 1992.
1989 Meyers-Wallen, V.N., Donahoe, P.K., Ueno, S., Manganaro, T.F., Patterson, D.F. :
Mullerian Inhibiting Substance Is Present in Testes of Dogs with Persistent Mullerian Duct Syndrome Biology of Reproduction 41:881-888, 1989. Pubmed reference: 2576223.
1982 Marshall, LS., Oehlert, ML., Haskins, ME., Selden, JR., Patterson, DF. :
Persistent Mullerian duct syndrome in miniature schnauzers. J Am Vet Med Assoc 181:798-801, 1982. Pubmed reference: 7141975.
1976 Brown, T.T., Burek, J.D., McEntee, K. :
Male pseudohermaphroditism, cryptorchidism and sertoli cell neoplasia in three miniature Schnausers Journal of the American Veterinary Medical Association 169:821-825, 1976. Pubmed reference: 10267.

Edit History


  • Created by Frank Nicholas on 09 Sep 2008
  • Changed by Vicki Meyers-Wallen on 11 Aug 2011
  • Changed by Frank Nicholas on 11 Aug 2011
  • Changed by Martha MaloneyHuss on 03 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011