Veterinarians examine, treat, and diagnose dogs with inherited diseases daily. Though treatments to fix some inherited disorders such as cryptorchidism and umbilical hernias are relatively safe and effective, rarely are the inherited disorders seen in practice remedied with a simple, relatively low-cost solution. In fact, in many cases of inherited disease, treatment options are extremely limited or non-existent. Therefore, an option to prevent these diseases before they occur would be preferable in most circumstances. Genetic disease testing made possible by the discovery of the causal mutations has become the best medicine to combat many inherited conditions.
Genetic testing of dams and sires has become commonplace in many dog breeds as breeders have recognized the power of identifying those dogs at risk of producing puppies with inherited diseases. Unfortunately, however, some breeders have been slow to adopt the routine use of genetic testing as they continue to rely on traditional selective breeding techniques. Limited by the inability to identify unaffected carriers of disease, selective breeding has historically proven relatively ineffective in the pursuit of large reductions in disease incidence.
Adult and late-onset inherited diseases pose an extra challenge in selective breeding because dogs become sexually mature before signs of the disease become apparent. In addition, breeders may not always be aware that their dogs are at risk of late-onset disease if their puppy buyers associate the disease with advanced age rather than inheritance. Therefore, when the owner brings that older, ailing critter to the veterinary hospital, those practitioners with a fundamental knowledge of what genetic disease testing is available can still play a role in disease prevention, even when there are no effective treatments for the dog in the exam room. With the diagnosis of a preventable inherited disease in hand, veterinarians who encourage owners to discuss genetic testing with their breeders and make themselves available to answer questions, yield the power to easily prevent tens or hundreds of future dogs from experiencing unnecessary suffering.
Here we discuss three adult-onset, preventable canine inherited diseases that are commonly seen in veterinary practice:
Progressive retinal atrophy (PRA) is the general name given to a group of similar eye diseases resulting in canine blindness, but each displaying a unique age of onset and course to complete blindness. Caused by a genetic mutation in the canine PRCD gene, a type of PRA known as progressive rod-cone degeneration (PRA-prcd) is by far the most common and widespread cause of PRA in the dog. Identified in over two dozen breeds, the widespread distribution of the PRCD mutation indicates that it likely originated in a common ancestor to many of our current breeds.
In general, PRA is marked by degeneration of photoreceptor cells (rods and cones) of the retina. Degeneration of rods and cones results in thinning of the retina and attenuation of retinal blood vessels which can be identified on eye exam. As the disease progresses, the optic nerve atrophies, leaving a dark optic disc. Hyperreflectivity of the tapetum caused by retinal thinning is common in late stages of disease. Early clinical signs of PRA are dictated by the general chronology of which photoreceptor type is affected first. In PRA-prcd, rod cells are affected first, resulting in initial clinical signs of night blindness. As the disease progresses and cone cells also degenerate, dogs will become completely blind. PRA-prcd displays an adult age of onset, but can be variable in the exact age of presentation. Though affected dogs can be identified with electroretinogram as early as 1 ½ years of age, it is common for them to develop first signs of night blindness around 3 to 5 years of age.
Like most types of PRA, PRA-prcd is inherited in an autosomal recessive fashion (rarer dominant and X-linked types also occur in dogs). This means that a dog must inherit two copies of the associated mutation (one from each parent) in order to develop the disease. Dogs inheriting a single copy of a recessive mutation are considered carriers of the disease and will not show features of the disease themselves. However, if bred with another carrier of the same mutation, carriers are at risk of producing affected puppies. Therefore, identifying carriers via genetic testing is of utmost importance in attempts to eliminate the disease from a blood line. By only allowing carriers to be bred to dogs that have not inherited the mutation, the breeder can avoid ever producing an affected puppy. As with most inherited diseases, it is not recommended to breed affected dogs because even if bred to a dog without the mutation, 100% of the puppies will be carriers. Thus, this practice significantly increases the frequency of the mutation in the population.
Though once most commonly associated with the German shepherd dog, the progressive neurological disease degenerative myelopathy (DM) and the associated SOD1 gene mutation have now been identified in over 100 breeds of dog. A close correlate to amyotrophic lateral sclerosis (ALS) of humans, DM results in progressive loss of motor function most commonly beginning between 7 and 10 years of age, though significant variability in age of onset can occur between breeds and individuals. The earliest clinical signs commonly include hind limb weakness and loss of conscious proprioception in the hind limbs. In these early stages, dogs may have difficulty climbing stairs and rising after laying down. As the disease progresses cranially to the front limbs, muscle atrophy, urinary and fecal incontinence, and the inability to walk often result in euthanasia due to quality of life concerns. Given the early clinical signs and the late age of onset, clients often attribute signs of DM to other geriatric conditions such as arthritis or the nebulous “slowing down” of advanced age; not necessarily worthy of their breeder’s attention.
Disease prevention considerations for DM are identical as those for PRA-prcd as it is also inherited in an autosomal recessive fashion. However, DM also displays the phenomenon known as incomplete penetrance, meaning that some dogs which inherit two copies of the causal mutation will not go on to develop disease. Though classic signs of axonal degeneration and demyelination have been reported in histological exams of spinal tissue from nonclinical homozygous mutants, some dogs will never reach the threshold necessary for clinical disease. This incomplete penetrance suggests that other genetic and environmental factors play a role in modulating the speed of disease progression. This assumption was supported by a study published by Ivansson and colleagues in 2016 which described variants in the canine SP110 gene responsible for modulating the age of onset in Pembroke Welsh Corgis homozygous for the DM mutation. Modifying factors in other breeds are still yet to be discovered.
Found in over a dozen terrier breeds and several others, primary lens luxation is a relatively common emergency to walk through the doors of most veterinary hospitals. Dogs inheriting a mutation in the canine ADAMTS17 gene develop structural abnormalities in the zonular fibers which play an important role in holding the lens of the eye in proper alignment. With time, progressive weakening of these fibers results in their rupture and the subsequent luxation of the lens; most commonly luxating cranially into the anterior chamber. Presence of the lens in the anterior chamber is considered urgent as glaucoma and blindness can occur rapidly as outflow drainage from the anterior chamber becomes compromised. Treatment consists of lens removal with or without replacement of an artificial lens.
Primary lens luxation is inherited in an autosomal incomplete dominant fashion. According to a study of Australian Tenterfield and miniature bull terriers by Gharahkhani and colleages, 100% of homozygous mutant dogs developed lens luxation by 6 years of age. Though less likely to suffer from primary lens luxation, 60% of dogs inheriting a single copy of the mutation developed primary lens luxation by age 10. Additional studies are necessary to examine if disease frequency in other breeds is similar when the mutation has been inherited.
Genetic Testing and The Future of Veterinary Medicine
As genetic testing for more canine conditions becomes possible, veterinarians will have an increasingly important role to play in helping dog breeders understand how certain diseases are inherited and in educating breeders how to meet their ultimate goal of producing beautiful, healthy puppies. Though treatment of inherited diseases can often be fruitless or merely symptomatic, with knowledge of available genetic disease tests or where to look for them, veterinarians can still have an impact on the canine population by sharing their knowledge and preventing future litters of diseased puppies from ever having to be born.
Contact Paw Print Genetics
If you have questions about a particular case you’ve seen in practice or would like to explore how genetic testing can improve your quality of medicine, please feel free to contact the Paw Print Genetics laboratory to speak with our fantastic staff of geneticists and veterinarians at Askus@pawprintgenetics.com or 509-483-5950 (Monday through Friday; 8 am to 5 pm Pacific time).