Genetic diseases are a significant concern for both mixed-breed and purebred dogs, often stemming from ancient genes that predate breed separation and are distributed throughout the domestic dog genome. While the incidence of these diseases can vary between breeds due to differences in gene pool frequencies, a hallmark of inherited conditions is their predictable onset and progression. Understanding these predictable triggers and modifying factors is crucial for improving diagnosis, treatment, and overall management of genetic disorders in dogs. By monitoring insurance claims and centralized hospital databases, veterinarians can identify the most common genetic diseases, which often involve complex inheritance patterns influenced by multiple genes and environmental factors. It is essential to recognize these genetic diseases as chronic conditions rather than episodic illnesses.
Allergic Skin Disease
Allergic skin disease, manifesting as chronic inflammatory otitis, recurrent hot spots, and pruritus, is among the most frequent presentations in veterinary practice. Both mixed-breed and purebred dogs are affected, with certain breeds exhibiting a higher predisposition. Research indicates that atopic dermatitis in Golden and Labrador Retrievers has a heritability of 47%, highlighting a substantial environmental contribution as well. A molecular genetic study in German Shepherd Dogs has identified a specific chromosome segment associated with this condition. Currently, no genetic liability tests are available for allergic skin disease. However, predictable seasonality, observed in 15% to 62% of affected dogs, allows for proactive management. Interventional measures to control pruritus should be implemented before the condition progresses.
Canine Hip Dysplasia
Hip dysplasia is the most prevalent inherited musculoskeletal disorder, affecting both mixed-breed and purebred dogs. Approximately 14.6% of dogs with submitted radiographs to the Orthopedic Foundation for Animals (www.ofa.org) are rated as dysplastic, though this figure likely underestimates the true prevalence. Smaller dogs with hip dysplasia may not exhibit the same level of pain and discomfort as larger breeds, suggesting a relationship between size, weight, and clinical presentation. Diagnosis is typically made through ventrodorsal radiographs or by assessing the distraction index. Palpable hip laxity can be an early indicator of hip dysplasia and subsequent osteoarthritic changes. Performing gentle Ortolani procedures during puppy examinations and checking for hip laxity under anesthesia during neutering are recommended. Early identification of severe hip laxity may warrant interventional surgery. Experimental development of estimated breeding values and genotypic breeding values using DNA marker panels aims to aid in selecting for hip normalcy. Breeders are encouraged to prioritize familial breadth and depth of normalcy, evident in vertical pedigrees.
Brachycephalic Obstructive Airway Syndrome (BOAS)
Brachycephalic Obstructive Airway Syndrome (BOAS) is a breathing disorder characterized by difficulty breathing in short-snouted and “bully” breeds, with Bulldogs, French Bulldogs, and Pugs being most commonly affected. This condition arises from a disproportionate relationship between skull structure and the soft tissues of the nose and pharynx. Clinical signs include dyspnea, exercise and heat intolerance, abnormal respiratory noises, cyanosis, syncope, and even death. One study reported that 16.7% of high-risk dogs succumbed to respiratory failure. BOAS encompasses several anatomical abnormalities, including stenotic nares, an elongated soft palate, everted laryngeal saccules, laryngeal collapse, and/or a hypoplastic trachea. Affected dogs may also experience facial skin fold dermatitis and corneal ulceration. Corrective surgeries, such as rhinoplasty for stenotic nares, soft palate resection, and laryngeal saccule removal, can significantly improve the quality of life for severely affected dogs. Responsible breeders should select for dogs exhibiting normal respiration, a defined muzzle, a normal tracheal diameter, and wide nostrils.
Myxomatous Mitral Valve Disease
Myxomatous mitral valve disease, also known as mitral valve endocardiosis, is predominantly observed in older toy breeds and small dogs. In certain breeds, such as the Norfolk Terrier and Cavalier King Charles Spaniel, it can lead to heart disease at an average age of 6.25 years. To address this, some Cavalier King Charles Spaniel clubs have implemented a generational breeding control program, restricting breeding to dogs free of murmurs and Doppler evidence of mitral regurgitation. This initiative has successfully reduced the frequency of the disorder.
Cranial Cruciate Ligament Rupture
While cranial cruciate ligament rupture is often viewed as a traumatic injury, studies indicate an increased risk in breeds like Rottweilers, West Highland White Terriers, Golden Retrievers, Yorkshire Terriers, Staffordshire Bull Terriers, and certain mixed breeds. Research on Newfoundlands suggests a heritability of 27% for this condition. Potential genetic predisposing factors include issues with ligament extracellular matrix metabolism, degeneration, and inflammation. Biomechanical and conformational variations, such as bone length, stifle angulation, tibial plateau variation, or a narrowed distal femoral intercondylar notch, can also contribute to the risk of rupture.
Patellar Luxation
Patellar luxation is a complex inherited disorder where the kneecap dislocates medially or laterally from the trochlea. It is more common in smaller breeds but also affects several larger breeds with a high incidence. The condition can range from subclinical to causing pain, instability, and arthritic changes. Weight management plays a crucial role in mitigating morbidity. Affected dogs typically progress through four grades of luxation over time. Breeders must utilize pedigree information to select against this disorder.
Hereditary Cancers
While all cancers involve mutations, some are considered hereditary due to inherited predisposing influences. Common hereditary canine cancers include lymphoma/lymphosarcoma, hemangiosarcoma, mast cell tumors, and osteosarcoma. Other genetically predisposed cancers include malignant melanoma, squamous cell carcinoma, mammary tumors, transitional cell carcinoma, and histiocytic sarcoma. Cancer susceptibility is linked to genes involved in cell surveillance and those that can promote malignant transformation. While numerous genetic anomalies are found in tumor tissues, their direct correlation to “cancer-causing genes” in the normal genotype is still under investigation. Current research is identifying genetic markers associated with increased cancer risk, which may eventually lead to screening tests for genetic cancer susceptibility.
Cryptorchidism
Retained testicles, or cryptorchidism, are frequently observed in both mixed-breed and purebred dogs, with a reported prevalence of 6.8%. This condition can be unilateral or bilateral and the retained testicle may be located abdominally or subcutaneously. Testes typically descend into the scrotum by eight weeks of age. Cryptorchidism is a sex-limited trait, meaning both sexes inherit the predisposition, but only males express it. Therefore, genetic control must involve selective breeding against female close relatives of affected males. Late descent of testicles, up to 14 weeks of age, is also an expression of the disorder and should be selected against.
Hypothyroidism
Hypothyroidism is a commonly reported disorder in dogs, caused by autoimmune thyroiditis where autoantibodies destroy thyroid hormone-producing tissue. Thyroid screening indicates that 6.3% of dog blood samples test positive for thyroglobulin autoantibodies (TgAA). However, the progression rate from positive TgAA to clinical hypothyroidism is not well-documented. Resting T4 measurements are unreliable indicators, as many dogs with non-thyroidal illnesses exhibit low T4 levels. Furthermore, numerous thyroid hormone-responsive conditions, such as obesity, lethargy, and poor coat quality, can mimic hypothyroidism. While autoimmune thyroiditis is a hereditary disease in dogs, it may be over- or misdiagnosed.
Inherited Cataracts
Many older dogs develop slowly progressive cataracts, and it is likely that all spontaneous cataracts have hereditary components. Eye screening programs have shown a reduction in cataracts in Dachshunds over time. A specific mutation (HSA1) causes autosomal recessive early-onset cataracts in Boston Terriers, Staffordshire Bull Terriers, and French Bulldogs. Another mutation in the same gene results in autosomal dominant early-age cataracts in Australian Shepherds. Numerous breed-related inherited cataracts are documented, with some breeds exhibiting multiple forms differentiated by age of onset, progression, and location within the lens. Further research is needed to uncover all causative mutations.
Other Common Genetic Disorders
Other frequently encountered genetic disorders in dogs include non-struvite bladder stones, elbow dysplasia, hepatic shunts, epilepsy, glaucoma, deafness, blindness, renal dysplasia, and Addison’s disease. Several Mendelian disorders have identified genetic tests, such as the prcd form of progressive retinal atrophy, mdr1-related drug sensitivity, arrhythmogenic right ventricular cardiomyopathy in Boxers, von Willebrand’s disease, and a liability gene for degenerative myelopathy.
Conclusion
The WSAVA Canine and Feline Hereditary Disease (DNA) Testing website is a valuable resource for DNA tests, lists of susceptible breeds, and testing laboratories. Dogs diagnosed with genetic disorders should not be used for breeding. Due to the complex inheritance of most genetic diseases, assessing genetic risk should be based on the clinical health of prospective breeding dogs’ first-degree relatives. Online health registry databases can facilitate this. Carriers of testable recessive disease-liability genes can be bred with normal-testing mates, and their normal-testing offspring can then be used for breeding. Dogs with testable dominant disease-liability genes should be replaced in breeding programs by normal-testing relatives.
