Ragdoll Genetic Issues
By Christine Lupo
Ragdoll Genetic Issues
By Christine Lupo
Some of the genetic mutations listed below occur in other breeds, such as the Persian and Birman, of which appear in many Ragdoll pedigrees; hence, the reason they are included on this page and should be tested. In the Cinnamon Ragdolls, there are Abyssinian, Selkirk Rex, and/or British Longhairs present in the background, so certain tests that pertain to these breeds should also be conducted for those Ragdolls with the aforementioned outcrosses in their pedigrees. Likewise, those breeders who have Maine Coon in their pedigrees, should test for both Ragdoll and Maine Coon HCM. ;)
A heart murmur may be heard by your vet when he or she listens to your kitten's heart. A heart murmur is caused by turbulent blood flow within the heart or the large vessels exiting from the heart. This results in an abnormal noise which can be heard by your vet when listening with a stethoscope. Kittens that might have a heart murmur should not be put under anesthesia, and surgery to spay and neuter should be put off until they are 5-6 months of age.
One type of innocent heart murmur is often found in young growing kittens, particularly kittens that are growing rapidly. The murmur may first appear at 6-8 weeks of age, and a kitten with an innocent heart murmur will usually outgrow it by about 4-5 months of age. This type of murmur is benign. Some normal adult cats may have an intermittent heart murmur that shows up when their heart rate is increased due to stress. This type of physiologic murmur disappears when the heart rate is normal, and has no impact on the cat's health.
In general, a physiologic or innocent heart murmur will have a low intensity (usually Grade I-II out of VI), and does not cause any symptoms or clinical signs. The symptoms associated with murmurs depend on a variety of characteristics, including their grade, configuration, and location. If, however, the murmur is associated with structural heart disease, your cat may display signs of congestive heart failure such as coughing, weakness, or exercise intolerance.
Grading Scale for Murmurs
Grade I—barely audible
Grade II—soft, but easily heard with a stethoscope
Grade III—intermediate loudness; most murmurs which are related to the mechanics of blood circulation are at least grade III
Grade IV—loud murmur that radiates widely, often including opposite side of chest
Grade V—very loud, audible with stethoscope barely touching the chest; the vibration is also strong enough to be felt through the animal's chest wall
Grade VI—very loud, audible with stethoscope barely touching the chest; the vibration is also strong enough to be felt through the animal's chest wall.
Heart murmurs are assessed and graded according to certain criteria. Grades I-VI are recognized, with Grade I being the most mild, and Grade VI the most severe. The grading system is based largely on how loud the murmur is, but other factors are also considered, such as the area over which the murmur is audible.
The grade of the heart murmur does not necessarily relate to the degree severity of the underlying heart problem. Some severe heart conditions may not be associated with any heart murmur at all, and some quite loud murmurs may occur with relatively small defects.
Although the presence of a murmur usually implies an underlying heart condition, murmurs can sometimes have other causes. In young kittens, so-called 'innocent' heart murmurs may be heard as an incidental finding. These are usually no longer present when the kitten is older. An innocent or physiologic heart murmur is a heart murmur that has no impact on the cat's health.
HCM (RD for Ragdoll and MC for Maine Coon)
Hypertrophic Cardiomyopathy (HCM) is the most common cause of heart disease and the most frequent cause of spontaneous death in indoor adult cats. In cats with this condition, the walls of the ventricles become thick. However, because the muscle fibers are replaced by fibrous connective tissue (scar tissue), the thicker heart walls do not translate into increased pumping power. In fact, the heart is actually weakened as the affected wall of the heart becomes less elastic and the heart chambers get smaller.
Early signs of hypertrophic cardiomyopathy are vague and indefinite. Increased heart rate and a murmur are common signs. Decreased appetite, weight loss, and an increase in respiratory rate may all be noted. Loss of pep and appetite and reduced exercise tolerance may go unnoticed, because cats are able to recognize their own physical limitations and restrict their activities accordingly. Other than possibly hearing a heart murmur, it is unusual to detect heart disease before signs of congestive heart failure. The first and only sign may be sudden death. (WebMD for cats)
The breed-specific mutation for HCM in Ragdoll cats produces early onset of the disease with average age at diagnosis of 15 months. It also appears that homozygotes (2 copies) for the mutation have an earlier age of onset of disease than heterozygotes (1 copy). The mutation, known as R820W, is a single base pair change in MYBPC3 that is thought to alter the shape and function of this essential protein for normal heart muscle development. The same R820W mutation has been recently found to be associated with HCM and left ventricular non-compaction in humans (see reference below, Ripoll et al. 2010. Veterinary Genetics Laboratory UC Davis).
MPS VI & VII
Mucopolysaccharidosis VI severe (MPS VIs) and mild (MPS VIm) are lysosomal storage diseases resulting from two independent mutations in the gene for enzyme N-acetylgalactosamine 4-sulfatase (4S). Both are inherited as autosomal recessives, thus males and females can be equally affected if they carry 2 copies of the defective gene. Cats with 2 copies of the severe form show signs at 6-8 weeks of age that include wide faces, shortened noses, small ears, reduced flexibility and retarded growth compared to unaffected littermates. By 8 months of age, problems of severe hind-limb mobility or paralysis, and signs of degenerative joint disease can be observed. Clinically, urine samples show increased levels of dermatan sulfate (DS) and an increase in white blood cell granules. Organs and tissues can also be compromised by accumulation of intercellular DS. Additional effects of the disease include corneal clouding and heart valve thickening. Cats with two copies of the mild form disease (MPSVIm) have less 4S enzyme and form granules in the white blood cells but otherwise appear healthy. The same is true of cats with one copy of the mild form and one copy of the severe form. Cats with only one copy (carrier) of either mutation and one copy of the normal gene appear healthy. Breeding two carriers together is predicted to produce 25% affected offspring and 50% carriers of the disease. Breeds at risk for MPSVIs and MPSVIm are Birman, Ragdoll, Siamese and related breeds, Domestic Shorthair.
Mucopolysaccharidosis VII (MPS VII) is a progressive, autosomal recessive disorder resulting from a single mutation in the GUSB gene that produces lysosomal enzyme B-glucuronidase. Disruption of this enzyme results in dermatan sulfate, heperan sulfate and chondroitin sulfate accumulation. By three months of age affected cats show clinical signs that include gait abnormalities, possibly due to muscle weakness, as well as bone abnormalities, disproportionate skull to body ratio, plump paws and corneal clouding, among other defects. Most affected animals must be euthanized by 6 months. Males and females are equally affected and carriers are normal and without sign of the disease. MPS VII has been reported in random bred cats (Veterinary Genetics Laboratory UC Davis).
Polycystic Kidney Disease (PKD) is an inherited disease
Primarily found in Persian cats, related breeds, and cats with Persian
ancestry. Other forms of PKD occur in other animals, and in humans. Feline polycystic kidney disease has been reported occasionally in the scientific literature since 1967, but actual study into this disease did not begin until 1990. In 2004, the mutation responsible for PKD in Persians and cats with Persian ancestry was identified. Multiple cysts develop in both kidneys, sometimes leading to chronic kidney insufficiency or failure. Rarely, cysts are also seen in other organs such as the liver and uterus. Problems occur when these cysts start to grow and progressively enlarge the kidney, reducing the kidney's ability to function properly. Some of the signs of kidney insufficiency are increased thirst, increased urination, decreased appetite, weight loss, vomiting, and lethargy. Cats affected by kidney insufficiency due to PKD are usually identified when they are between three and ten years of age. They are treated as for any other cause of chronic kidney disease as no specific treatment for PKD is available. PKD can be diagnosed by ultrasound of the kidneys. There is also a genetic test for PKD in Persian cats and cats with Persian ancestry (Winn Feline Foundation).
Progressive Retinal Atrophy (PRA) in Abyssinian, Somali and some Ocicat breeds, is an inherited late-onset blindness condition has been identified and is characterized by progressive degeneration of the photoreceptors (rods and cones) in the retina. This disease has been designated "rdAc". Cats affected with this form of blindness have normal vision at birth, with degeneration first detected by electroretinographic (ERG) exam at about seven months of age. Vision loss progresses slowly and is variable, with most cats becoming blind by usually 3-5 years of age. There is no treatment available for the condition. This is an autosomal recessive condition, thus the disease is not associated with gender and two copies of the mutation are required for the cats to lose their vision. Carriers, cats that have one copy of the mutation, are not affected and have normal vision (Veterinary Genetics Laboratory UC Davis).
FELINE BLOOD GROUPS
There are three feline blood types: A, B and AB. The A type is the most common in cats. The prevalence of type B blood differs by breed. There is a high occurrence of Type AB in the Ragdoll Breed. Cats have naturally occurring antibodies ( a protein made by the body's immune system that latches onto foreign particles, such as viruses, bacteria, other proteins, to make them ineffective by destroying them) to antigens (foreign proteins) not on their erythrocytes. Erythrocytes are Red blood cells (RBCs). In medical terminology, erythro- means red, while -cyte means cell. Erythrocytes are red and consist of a protein called hemoglobin, which contains red iron. This is why our blood is red in color. Erythrocytes are round and perform two functions of gas exchange: transport oxygen and remove carbon dioxide.
Cats with type A blood have antibodies to type B antigens, and cats with type B blood have antibodies to type A antigens. Cats with type AB blood have both A and B antigens on the erythrocyte membrane and do not have naturally occurring antibodies to either type A or B blood. Cats with the rare "AB" type do not have anti-A or anti-B antibodies and are thus universal recipients for blood transfusion.
Cats that are transfused, even once, with an incompatible blood type, are at risk for a transfusion reaction. Cats with B erythrocytes exhibit an immediate and catastrophic systemic reaction when transfused with type A blood, because of their natural high anti-A antibody Death is extremely likely.
Cats with A erythrocytes and natural low anti-B antibody will exhibit only a mild reaction when transfused with type B blood, but the transfused cells will have a shortened life span. The recipient will develop moderate concentration of anti-B antibody that will result in a serious reaction if a subsequent incompatible transfusion is administered. If there is a need to treat a blood disorder or trauma, knowing the patient’s blood type can help prevent an emergency.
Serious problems can result from accidental or mismatched mating.
A mating of a type B queen with a type A tom will result in their type A kittens being at risk for neonatal isoerythrolysis (“NI”), commonly known as “fading kitten syndrome”. The maternal naturally occurring, highly concentrated anti-A antibody occurs in the colostrum (mother's milk) where it can be absorbed by the newborn kittens. The absorbed antibody attacks the kittens’ type A erythrocytes. Although the kittens can seem normal at birth, they develop signs after nursing, fade and die within the first days of life. Determining the blood type of the queen and the tom prior to mating,can minimize the risk of NI. Furthermore, immediate blood type determination of the newborn kittens will alert the breeder to remove the kittens and to begin surrogate nursing where necessary.
• All cats should be blood typed.
• No cats should be mated before blood typing.
• All kittens resulting from incompatible matings should be blood typed at birth so that surrogate nursing can be started where necessary and the kittens allowed to thrive.
Winn Feline Foundation
Veterinary Genetics Laboratory UC Davis
MPS & HCM website and directory of results
Veterinary Genetics Laboratory UC Davis
Information about Diseases and Testing