Vizsla — XX sex reversal, XX DSD testicular/ovotesticular (hereditary; OMIA-verified breed predisposition)

--- license: permission_granted topic_id: companion_breed_health_vizsla_xx_sex_reversal_xx_dsd_testicular_ovotesticular_dog category: companion-breed-health title: "Vizsla — XX sex reversal, XX DSD testicular/ovotesticular (hereditary; OMIA-verified breed predisposition)" lang: en source: "OMIA (Online Mendelian Inheritance in Animals, University of Sydney) breed-specific hereditary-disorder record, saved verbatim to source_file; C1 substring-verified. Pulled 2026-08-02 from local OMIA database dump." source_file: pdf-raw/breed-health/vizsla_xx_sex_reversal_xx_dsd_testicular_ovotesticular_1946.txt date_parsed: 2026-08-02 tokens_estimated: 2075 verification: method: substring_match claims: 10 passed: 10 date: 2026-08-02 recovered: false path: companion-breed-health/companion_breed_health_vizsla_xx_sex_reversal_xx_dsd_testicular_ovotesticular_dog/01_companion_breed_health_vizsla_xx_sex_reversal_xx_dsd_testicular_ovotesticular_dog.md source_document: "OMIA — Online Mendelian Inheritance in Animals (University of Sydney)" citation: authority: "OMIA — Online Mendelian Inheritance in Animals (University of Sydney)" title: "Vizsla — XX sex reversal, XX DSD testicular/ovotesticular (hereditary; OMIA-verified breed predisposition)" url: "https://omia.org/OMIA000901/9615/" retrieved: "2026-08-02" ref: "OMIA breed-specific hereditary-disorder records (omia.org), derived from local OMIA database dump; dataset: https://doi.org/10.25910/2AMR-PV70" doc_type: "academic animal-genetics database (breed-specific disorder entries)" needs_review: false

Vizsla — XX sex reversal, XX DSD testicular/ovotesticular (hereditary; OMIA-verified breed predisposition)

Source: first-hand OMIA (University of Sydney) breed-specific hereditary-disorder record, saved verbatim to source_file; every claim below is a C1 byte-substring of it.

Claims

• Breed: Vizsla (Dog)
• Disorder: XX sex reversal, XX DSD testicular/ovotesticular
• Mode of inheritance: Multifactorial
• Summary: Canine XX sex reversal is a type of XX disorder of sexual development (XX DSD, Pasterski et al 2010) characterized by presence of testicular tissue in the gonads and varying degrees of phenotypic masculinization in dogs that have a female karyotype (78, XX). As both Sry and the Y chromosome are absent in affected dogs, it is called Sry-negative XX sex reversal. Diagnosis is dependent upon karyotype (78,XX), PCR assay confirming that Sry is absent, and histology confirming the presence of testicular tissue in the gonads. This XX DSD has been identified in at least 28 pure bred dogs. It has been most extensively studied in the American cocker spaniel (ACS), in which the mode of inheritance is sex-limited autosomal recessive. Studies in the ACS indicate that approximately 10% of affected dogs develop bilateral testes (XX male, testicular XX DSD) and 90% develop ovotestes ( XX true hermaphrodite, ovotesticular XX DSD). Affected dogs with bilateral testes are sterile, as are most with ovotestes. However, affected dogs in the latter category have rarely reproduced as females. Carrier dogs are fertile. To prevent production of affected dogs, breeding of affected or known carrier dogs should be avoided. SRY-negative XX sex reversal has now been reported in at least 28 breeds and mixed breeds, although not all were tested for SRY, as the PCR assay for canine SRY was not available prior to 1995 ([Meyers-Wallen et al., 1995a) . While this disorder may be genetically heterogeneous in the dog population in general, the mutation is likely to be identical by descent in closely related breeds, such as English and American cocker spaniels. Normal mammalian prenatal sexual development depends upon the serial completion of three steps. The first is normal segregation of the sex chromosomes into the gametes, so that at fertilization, the zygote contains two sex chromosomes, either XX or XY. The second step is to translate chromosomal sex into gonadal sex, with XX individuals developing an ovary and XY individuals developing a testis. In mammals, gonadal sex is determined by genes on the autosomes and sex chromosomes. The third step is differentiation of the internal and external genitalia, which depends upon testicular hormones and their receptors and signaling pathways in target organs. Masculinization of the genitalia occurs in response to testis hormones, whereas female genitalia develop in their absence. Gonadal development begins with the emergence of the bipotential gonad. Shortly thereafter in XY embryos, a gene on the Y chromosome, SRY (sex determining region Y), dramatically upregulates an autosomal gene, SOX9 (SRY related HMG-box protein 9) during the critical period for Sertoli cell differentiation, which initiates testis development. Several other genes play a role in upregulating and maintaining SOX9 expression in the testis. In the ovarian pathway, R-spondin1 (RSPO1), a gene in the wingless-related protein family (WNT) signaling pathway, has a role in suppressing SOX9-mediated testis pathways in the developing ovary (reviewed in Jakob and Lovell-Badge, 2011). Both WNT4 and RSPO1 signaling lead to an increase in stabilized beta catenin. Recent evidence indicates that SOX9 and beta catenin act antagonistically (reviewed in Jakob and Lovell-Badge, 2011). Changes in gene expression in either the testis or ovarian pathway can disrupt gonadal development, leading to development of testes or ovotestes in XX individuals. Molecular mechanisms reported for development of testes or ovotestes in XX individuals of other species include: 1) SOX9 upregulation during gonadal development induces testis development, either by duplication of SOX9 in XX humans (Huang et al 1999, Cox et al 2011, Vetro et al 2011) or by transgenic manipulation in XX mice (Bishop et al. 2000). 2) Mutations that eliminate or reduce RSPO1 expression. A null RSPO1 mutation induced testis development in related XX individuals (Parma et al. 2006), while a different RSPO1 mutation induced ovotestis development in another family (Tomaselli et al. 2008). Transgenic RSPO1 null mice develop ovotestes, not testes (Chassot et al. 2008). 3) SOX3 upregulation during gonadal development induces testis development, either by genomic rearrangement of its regulatory regions in XX humans, or transgenically in XX mice (Sutton et al. 2011). 4) Mutations that eliminate FOXL2 or PISRT1 expression induce testis development in XX polled goats (Pailhoux et al. 2001, Pannetier et al. 2005). This mechanism has not been identified as a cause of XX sex reversal in other species, and human FOXL2 mutations are associated with premature ovarian failure (De Baere et al. 2003). The ACS model is strikingly similar to the subcategory of human XX DSD in which testes or ovotestes develop in 46,XX siblings, or within the same family, and the genetic defect is unknown [Skordis et al., 1987; Ostrer et al., 1989; Palmer et al., 1989; Kuhnle et al., 1993; Ramos et al., 1996; Slaney et al., 1998]. No candidate genes have yet been linked to the affected phenotype in dogs from the ACS research model (Kothapalli et al., 2003; Kothapalli et al., 2004; Kothapalli et al., 2005; Kothapalli et al., 2006; Pujar et al., 2005). ]. Exon scanning ruled out mutations in the coding region of canine RSPO1 in affected dogs of most breeds in which XX DSD has been reported [DeLorenzi et al., 2008]. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT in 2001; updated by FN in 2015.
• Clin feat: Affected dogs (XX male, testicular XX DSD) are most appear as bilaterally cryptorchid male dogs, but have a caudally displaced and pendulous prepuce and hypoplastic penis. Mild hypospadias may also be present. These dogs are sterile (Meyers-Wallen et al., 1988). Variable degrees of masculinization are found in affected dogs with ovotestes (XX true hermaphrodite, ovotesticular DSD). Those most masculinized have an enlarged clitoris containing a bone and/or a misshapen vulva that resembles a prepuce. Clitoral enlargement may be noted within a few months of age or at puberty. Many XX true hermaphrodites in the ACS studies had an apparently normal female external phenotype (Meyers-Wallen and Patterson 1988). Affected dogs with ovotestes may exhibit estrous cycles and rarely, produce offspring. Both XX males and XX true hermaphrodites can occur within the same litter or in the same pedigree.
• Defect: yes
• Pathology: A spectrum of phenotypic variation correlated to the amount of testicular tissue present in the individual was identified in studies of affected ACS dogs (Meyers-Wallen et al., 1988), as follows: 1) XX males with bilateral testes had bilateral epididymides, a prostate, Wolffian duct derivatives, and a complete uterus. The external genitalia included a caudally displaced and pendulous prepuce, hypoplastic penis and usually bilateral cryptorchidism . 2) True hermaphrodites with unilateral or bilateral ovotestes had oviducts and/or epididymides, and a complete uterus. Externally, an enlarged clitoris with a bone and/or misshapen vulva resembling a prepuce, was present in some. In others, the external genitalia had a female phenotype 3) True hermaphrodites with one ovotestis had bilateral oviducts, a complete uterus, and normal female external genitalia. Although biologically active Müllerian inhibiting substance (MIS) is present in neonatal testes and ovotestes from affected dogs, the timing of MIS secretion is delayed. This could explain why the cranial Müllerian ducts regress but the uterus remains (Meyers-Wallen, 2011).
• Prevalence: SRY-negative XX sex reversal has been identified in at least 28 dog breeds and a mixed breed dog.
• Control: While XX males are sterile, some XX true hermaphrodites have exhibited estrous cycles and reproduced as females. Breeding of true hermaphrodites or parents of affected dogs should be discouraged.
• Gen test: Diagnosis is dependent upon karyotype (78,XX), PCR assay confirming that SRY is absent in genomic DNA, and histology confirming the presence of testicular tissue in one or both gonads (ovotestes or testes).

Associated gene(s)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• OMIA entry symbol: XXSR (no structured Phene_Gene link)
• OMIA molecular-genetics note: Rossi et al. (2014) reported a duplication of a 577kb region on chromosome CFA9 (from 11,016,965 to 11,593,933; CanFam2 genome assembly) containing SOX9, a gene with a central involvement in sex determination, in 2 of 7 cases of this disorder. From a larger study involving 16 affected and 30 control dogs, Marcinkowska-Swojak et al. (2015) concluded that "Our extensive studies have excluded duplica…

Evidence (references)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• 1988. XX sex reversal in the American cocker spaniel dog: phenotypic expression and inheritance. Human Genetics — PubMed:PMID3417302 — OMIA Phene_Article / Article
• 1986. [A rare case of true lateral hermaphroditism in a 78,XX bitch]. Recueil de Medecine Veterinaire — OMIA Phene_Article / Article
• 1987. Mullerian inhibiting substance in sex-reversed dogs. Biology of Reproduction — PubMed:PMID3689844 — OMIA Phene_Article / Article
• 1990. Male pseudohermaphroditism - A case of a 78,XX intersex. Recueil de Medecine Veterinaire — OMIA Phene_Article / Article
• 1986. [Canine male pseudohermaphroditism with female chromosomal pattern]. Journal of the Japan Veterinary Medical Association — OMIA Phene_Article / Article
• 1991. XX true hermaphroditism in a Dog. J Am Vet Med Assoc — PubMed:PMID2010338 — OMIA Phene_Article / Article
• 1993. Genetics of sexual differentiation and anomalies in dogs and cats. J Reprod Fertil Suppl — PubMed:PMID8229960 — OMIA Phene_Article / Article
• 1994. Mullerian-inhibiting substance secretion is delayed in XX sex- reversed dog embryos. Molecular Reproduction and Development — PubMed:PMID7999353 | DOI:10.1002/mrd.1080390102 — OMIA Phene_Article / Article
• 1995. SRY-negative XX sex reversal in the American Cocker Spaniel dog. Molecular Reproduction and Development — PubMed:PMID8588928 | DOI:10.1002/mrd.1080410304 — OMIA Phene_Article / Article
• 1995. SRY-negative XX sex reversal in the German Shorthaired Pointer dog. Journal of Heredity — PubMed:PMID7560873 — OMIA Phene_Article / Article
• 1997. Pyovagina and stump pyometra in a neutered XX sex-reversed Beagle - a case report. Journal of the American Animal Hospital Association — PubMed:PMID8974032 — OMIA Phene_Article / Article
• 1999. Inherited disorders in sexual development. Journal of Heredity — PubMed:PMID9987911 — OMIA Phene_Article / Article
• (39 additional references in OMIA)

verification_derived: method: derived_from_dataset source: "OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM" note: "Structured fields (gene, variant rsID/protein change, PubMed/DOI references, OMIM cross-link) extracted from OMIA dump and presented with first-hand values; not verbatim prose."