{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:26Z","timestamp":1792788386548,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["DWD\/6\/00193\/2022"],"award-info":[{"award-number":["DWD\/6\/00193\/2022"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Myxomatous mitral valve disease (MMVD) is the most prevalent cardiac disorder in small and toy breed dogs, with the Cavalier King Charles Spaniel (CKCS) showing exceptionally high predisposition and early onset of the disease. MMVD is characterized by progressive mitral valve degeneration, volume overload, and eventual development of congestive heart failure (CHF). Given the strong hereditary component in CKCS, considerable research has focused on elucidating the genetic basis of MMVD in this breed. This review article summarizes the current state of knowledge on the phenotypic features, inheritance, and candidate loci potentially responsible for early onset and severe course of the disease. The pathogenesis of the disease, its classification, and the effects of breeding programs aimed at reducing the occurrence of MMVD have been described. Key findings include associations between MMVD severity and polymorphisms in genes such as NEBL, ACE, CDK6, HEPACAM2, COL5A1, and FAH, as well as evidence implicating dysregulated TGF-\u03b2 signaling, serotonin signaling, and extracellular matrix remodeling pathways. The current state of knowledge on the role of miRNA in the pathogenesis of MMVD was also summarized. Despite these findings, no specific high-penetrating mutation has been identified. MMVD is a complex, polygenic condition shaped by regulatory variants and breed-specific genetic bottlenecks. Comparative studies underscore the translational relevance of canine MMVD to human mitral valve disease, while genomic insights may be basis for the future selective breeding strategies and therapeutic approaches. Further large-scale, integrative studies combining genomics, transcriptomics, and functional validation are needed to clarify disease mechanisms and support targeted treatment in CKCS as well as the development of new breeding strategies and programs.<\/jats:p>","DOI":"10.3390\/vetsci12121144","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"1144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Basis of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniel Dogs\u2014A Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0596-8643","authenticated-orcid":false,"given":"Maksymilian","family":"Lewicki","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Wroc\u0142aw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-7216","authenticated-orcid":false,"given":"Sylwia Barbara","family":"G\u00f3rczy\u0144ska-Kosiorz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Diabetology and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6688-3051","authenticated-orcid":false,"given":"Piotr","family":"Frydrychowski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Wroc\u0142aw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzanna","family":"Sidoruk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Wroc\u0142aw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-3936","authenticated-orcid":false,"given":"Agnieszka","family":"Noszczyk-Nowak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Wroc\u0142aw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/j.1939-1676.2009.0392.x","article-title":"Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease","volume":"23","author":"Atkins","year":"2009","journal-title":"J. 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