Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA
As practitioners, we deal with genetic disease every day in our practice in purebred, cross-bred, and mixed-breed dogs and cats. Data from veterinary insurance claims help us determine the most frequent or common genetic disorders. The highest frequency genetic disorders are due to ancient mutations that occur across all mixed-breed and purebred dogs and cats. Some mutations are more recent, and are limited to only a few breeds or a single breed. For locations of genetic testing laboratories, please refer to the WSAVA Hereditary Diseases Committee Genetic Testing Laboratory Database: http://research.vet.upenn.edu/Default.aspx?TabId=7620.
Feline Genetic Disorders
As the majority of the cats seen in practice are random-bred domestic cats, ancient disease liability genes have been randomized in the population. The most frequent feline genetic disorders occur in this group.
The most frequent feline genetic disorder seen in practice is sterile feline lower urinary tract disease (FLUTD or FUS), with or without inflammatory cystitis (IC). This disease syndrome occurs in approximately 4% of all cats. For those cats predisposed to crystal formation and obstruction/irritation, genetic counseling recommendations include changing to a low Mg food, producing a lower urine pH, and increasing hydration (lowering urine specific gravity). The predisposition to develop IC is also genetic. Additional recommendations for IC include environmental modification to reduce stress and NSAIDs. Bladder stones are frequently diagnosed in cats. While struvite urolithiasis is caused by infection, calcium oxalate and other stones have a hereditary predisposition.
Chronic kidney disease is frequently diagnosed and is usually age related. The most frequent single-gene feline disorder seen in practice is polycystic kidney disease (PKD), caused by a testable autosomal dominant gene. This defective gene is present at a high frequency (38% testing positive) in Persian, Himalayan, and Persian-derived breeds. The majority of affected cats will develop kidney failure at an average age of 7 years (4 to 10 years).
If a client wants to purchase a kitten from a susceptible breed, they should ask for the PKD test results on both parents, or on the kittens. If the breeder offers that their breeding stock was ultrasounded clear of PKD, they are using an outdated and unreliable diagnostic standard. If valid PKD test results are not available for your client, then have them cheek swab kittens, and send them in for testing prior to purchasing a kitten.
Cats prone to lymphocytic/plasmacytic and eosinophilic inflammatory disease can present with gastrointestinal, dermatological, and oral/dental disease. These are complexly inherited predispositions and affected cats should be selected against for breeding.
Aside from being seen most frequently in domestic cats, Burmese cats have a significantly higher incidence of Type II diabetes. No genetic susceptibility tests are available. Obesity avoidance through dietary control is the best genetic counseling that can be offered to try to prevent its occurrence.
Autosomal dominant hypertrophic cardiomyopathy occurs in the Maine Coon Cat (33.4% affected based on DNA testing at Dr. Meur's laboratory at North Carolina State University). The disease causes sudden death or heart failure from 6 months to 7 years of age. Homozygous affected cats have an earlier onset or more severe form of the disease. The disorder shows incomplete penetrance, indicating that not all cats with the mutation will develop HCM. Your clients should insist on DNA testing before purchasing a Maine Coon Cat. The Ragdoll breed has HCM due to a different mutation in the same gene, but at a much lower frequency. For both breeds, there are mutation-negative cats with HCM, so this mutation is not the only cause of the disease.
Spina bifida is an autosomal dominant disorder seen in Manx cats, with variations in expression and possibly penetrance. It is a variation of expression of the tailless phenotype selected for in the breed. It is especially seen in tailless Manx to tailless Manx breedings, so many breeders maintain "stumpy" Manx cats with a shortened tail for breeding.
Polydactyly: Multiple toes is a common autosomal dominant trait with high penetrance and variable expression (numbers of toes). All cats with polydactyly usually have a similarly affected parent. Deafness with blue eyes: The autosomal dominant white (W) gene can cause deafness in cats. The gene shows incomplete penetrance. Not all white, blue-eyed cats are due to the W gene, and therefore can have normal hearing.
There are several rarer breed-specific genetic diseases with available genetic tests. These include Burmese autosomal recessive lethal cranio-facial defect, Burmese autosomal recessive hypokalemia, both an autosomal recessive and an autosomal recessive progressive retinal atrophy in Abyssinian and related breeds, and others.
Canine Genetic Disorders
The most common canine genetic disorders are also due to ancient mutations that are spread across purebred and mixed breed dogs. Selective breeding has caused some breeds to have higher frequencies, while some have lower frequencies of these diseases.
The most frequently diagnosed disorders in dogs are skin allergies, ear infections, and skin infections. It is recognized that allergic reactivity is specific to individual patients, and it is found that genetic liability to atopic dermatitis is 47% heritable. Affected dogs should be selected against for breeding.
Arthritis is a common diagnosis in dogs. It is well established that hip dysplasia, patella luxation, elbow dysplasia, osteochondritis dessicans, hypotrophic osteodystrophy (HOD) and panosteitis have genetic influences.
Hip dysplasia occurs across all mixed-breed and purebred dogs. Small dogs with hip dysplasia do not usually show the same pain and discomfort seen in larger affected dogs. Hip dysplasia is usually controlled through a radiograph evaluation (see the lecture "Clinical and Breeding Management of Canine Hip Dysplasia" for details). Weight restriction, chondroprotectants (as a treatment, not a preventative), and NSAIDs can control clinical signs of discomfort. There are both preventative (triple pelvic osteotomy or juvenile pubic symphysiodesis) and salvage (femoral head and neck in small dogs or total hip replacement in large dogs) surgical procedures.
Elbow dysplasia is a complexly inherited disorder of uncoordinated growth between the radius and ulna. It can present as ununited anconeal process (UAP), fractured coronoid process (FCP) or osteochondritis dessicans (OCD) of the elbow joint. Of all dogs with radiographs submitted to the OFA, 15.42% are rated with elbow dysplasia (See 2015 WSAVA Conference: International Elbow Working Group seminars.)
Anterior cruciate ligament rupture is a common traumatic injury whose predisposing factors may involve anatomical and conformational variation of the stifle joint. A study of ACL rupture in Newfoundlands showed 27% heritability.
Brachycephalic syndrome: The brachycephalic syndrome is a disorder of breathing difficulty in short-snouted breeds. It has become an issue due to breeding towards an extreme head type that does not allow normal breathing and air flow. It can cause collapse and sudden death due to overheating or lack of oxygen. The syndrome includes tight nostrils (stenotic nares), an elongated soft palate, everted laryngeal saccules, laryngeal collapse, and/or a narrow (hypoplastic) trachea. Breeders should select for a normal diameter trachea, nostrils that are 33% of the width of the nose and for a defined muzzle.
Hereditary epilepsy represents a diverse group of recurring seizure conditions and is considered a significant problem in over twenty breeds. As with human epilepsies, there will be many different epilepsy liability genes affecting many different breeds, and even within breeds.
The most frequent malignant canine cancers are lymphoma, hemangiosarcoma, mast cell tumor and osteosarcoma. These are seen with increased breed prevalence, familial prevalence and in individual mixed-breed and purebred dogs. Research is focusing on identifying inherited mutations that can provide both prognostic as well as preventative test results.
Heart disease encompasses congenital heart anomalies (patent ductus arteriosus [PDA], aortic stenosis); primary heart muscle disorders (cardiomyopathies); acquired valvular disease; and primary arrhythmias (Boxer arrhythmogenic right ventricular cardiomyopathy, sick sinus syndrome, and fatal arrhythmia in German Shepherd Dogs).
Retained testicles: This is a sex-limited genetic disease, where it is inherited from both parents, but only male dogs manifest the condition. Dogs with late descending testicles also carry liability genes for cryptorchidism. Umbilical hernias occur most frequently at the umbilicus or inguinal canal. These have a complex mode of inheritance. Affected dogs and their close relatives should be considered to carry an above average genetic load of hernia liability genes.
Drug sensitivity/ivermectin sensitivity: A mutation in the MDR1 or multi-drug resistance gene causes neurotoxicity from ivermectin, loperamide (Imodium), vincristine, and other drugs. Heterozygous carriers can be sensitive at high dosages. Most affected breeds are from the Collie lineage, and a DNA test is available.
There are several ocular disorders with DNA tests available, including progressive retinal atrophies (PRA), some cataracts, and lens luxation.
Hypothyroidism, nonstruvite bladder stones, inflammatory GI disease, liver shunts, von Willebrand disease, glaucoma, deafness, renal dysplasia, diabetes, and Addison's disease are also commonly seen hereditary disorders in dogs.
As veterinarians, we should be aware of the proper phenotypic and genotypic tests to diagnose these disorders. We should also be knowledgeable about the proper genetic counseling recommendations to prevent them or lessen their severity in our patients.