Genetic Diseases

Most genetic diseases are caused by mutations in the DNA. When two dogs that carry a mutated gene reproduce, their offspring are likely to be affected by the disease if they inherit two copies of the mutated gene. Unfortunately, some genetic defect diseases have developed from selective or inbreeding dogs.

The resulting puppies can be Affected, Carriers or Clear of the disease, if tested. If both the puppies’ parents are tested the puppies can be classed as Hereditary Clear, Hereditary Carrier, Hereditary Affected

The diseases tested for are:

• Blood
• Cardiac
• Dwarfism
• Eye Conditions
• Hereditary
• Immune
• Kidney
• Lysosomes Storage
• Muscular
• Nervous System
• Neurological
• Skeletal
• Skin

Blood Disorders

Glanzmann’s Thrombastenia (GT):

• GT is a bleeding disorder caused by a dysfunction in blood clotting. There are three types; type 1 type 2 and variant GT. Type 1 is the most severe, variant GT being relatively normal but with reduced function in clotting. Symptoms include prolonged bleeding, severe bruising, red or purple spots under the skin, nose bleeds, bleeding gums, and pin-prick blood spots on the abdomen. This is present from birth and affected dogs tend to be smaller than the breed average.
• Affected Breeds: Otterhound, Pyrenean Mountain Dog

Factor VII deficiency (FVIID)

• This is a disorder that affects blood clotting. Due to the lack of Factor VII dogs affected with this will have prolonged bleeding after surgery or trauma. Clinical signs won’t be evident until a dog has had surgery or an accident where the plonged bleeding can be noticed.
• Affected Breeds: Airedale Terrier, Alaskan Klee Kai, American Foxhound, Beagle, Papillion, Deerhound, Finnish Hound, German Wirehaired Pointer, Giant Schnauzer, Irish Water spaniel, Japanese Spitz, Miniature Schnauzer, Sealyham Terrier, Welsh Springer Spaniel

Haemophilia A (factor VIII deficiency / F8)

• Factor VIII deficiency is a type of blood clotting disorder, where affected dogs will bleed spontaneously into their chest, abdomen or joints. They will also develop significant bruising and profuse bleeding after a trauma or surgery. As this condition is sex-linked it means male dogs present this disorder if they have one mutated X-chromosome, the mutation usually comes from the mother. In most examples, the females carry one mutated X chromosome without being affected. Females only are affected when they carry two mutations, coming from both parents. This disorder is usually diagnosed in puppies or young adult dogs but can be diagnosed at any age. Puppies may have abnormal bleeding whilst teething. Other signs are extensive bruising or bleeding after trauma. Where spontaneous bleeding occurs, you may notice swollen joints, difficulty breathing or a drooping abdomen.
• Affected Breeds: German Shepherd Dog, White Swiss Shepherd Dog

Haemophilia B (Factor IX deficiency)

• This blood clotting disorder results in a lack of protein factor IX. With the lack of this protein the blood has problems coagulating leading to prolonged bleeding after trauma or surgery, female dogs may also experience issues after whelping. The condition is sex-linked which means male dogs present this disorder if they have one mutated X-chromosome, the mutation usually comes from the mother. In most examples, the females carry one mutated X chromosome without being affected. Females only are affected when they carry two mutations, coming from both parents.
• Affected Breeds: Afghan Hound, Airedale Terrier, Bull Terrier, Cairn Terrier, German Wirehaired Pointer, Lhasa Apso, Rhodesian Ridgeback

von Willebrand disease (vWD)

• Von Willebrand disease is a lack of von Willebrand’s Factor (vWF) a protein that plays a key part in blood clotting. vWD comes in three types: type 1, type 2 and type 3. Type 3 is the most severe and type 1 is the least severe. Dogs with vWD are prone to nose bleeds, bleeding from gums, and prolonged bleeding on heat or after whelping. For puppies there can be prolonged bleeding from the umbilical cord at birth or when teething. vWD suffers commonly have excessive bleeding after surgery or trauma, this could be the first sign of the disease for your dog. Some dogs present with blood in their urine or stool. The effects can widely range between individual dogs with some hardly showing typical signs.
• Affected Breeds:
• Type I: Dobermann, Irish Red And White Setter, Manchester Terrier, Barbet, Black And Tan English Toy Terrier, German Pinscher, Miniature Poodle, Papillon, Pembroke Welsh Corgi, Schipperke, Stabyhoun, Standard Poodle, Toy Poodle
• Type II: German Wirehaired Pointer, Chinese Crested Dog
• Type III: Kooikerhondje, Scottish Terrier, Shetland Sheepdog.

Phosphofructokinase deficiency (PFK)

• PFK affects the red blood cells and muscle cells. Affected dog’s have a lack of the phosphofructokinase enzyme which means the red blood cells and muscle cells aren’t able to produce enough energy for their needs. It results in the dog having weakness, lethargy, uninterest in exercise, muscle cramps, anaemia, jaundice and dark urine.  Dark urine is the main marker for the disease and usually appears after heavy exercise or after excessive barking, panting or heat exposure.
• Affected Breeds: English Springer Spaniel, Cocker Spaniel

Cardiac Disease

Rhodesian Ridgeback Inherited Ventricular Arrhythmia (IVA)

• This is a condition that results in abnormalities in the cardiac electrical system which develops the heartbeat. It results in abnormal heartbeats which can result in sudden death. It appears the most severe part of the disease is present between 6 and 30 months of age and many dogs appear to outgrow the problem. The testing will determine if your dog is at risk of this condition. Dogs that present with the gene mutation should have a heart monitor test done routinely between 6 and 30 months to monitor the condition.
• Affected Breeds: Rhodesian Ridgeback

Dilated cardiomyopathy (DCM)

• DCM is a condition of the heart which causes swelling of the lower heart chambers (ventricles). This restricts the heart’s ability to pump blood and leads the heart to become large and beat weakly. Signs can include collapsing, appetite loss, lethargy, abdominal swelling, cough or gasping for breath. The signs may not show for years but will be obvious eventually.
• Affected Breeds: Giant Schnauzer, Schauzer, Doberman, Estrela Mountain Dog, Great Dane

Juvenile Dilated Cardiomyopathy (JDCM)

• JDCM is a heart disease that affects young dogs. Affected dogs often appear healthy with no signs of heart disease but will unexpectedly pass. The only physical signs that may occur are affected young males may have undescended testicles (one or both). For many of the affected puppies, their passing can occur after having surgery, being under general anaesthesia, or exercising.
• Affected Breeds: English Toy Black and Tan Terrier, Manchester Terrier, Portuguese Water Dog.

Dwarfism

Chondrodysplasia (CDSL)

• CDSL is a type of dwarfism that affects the way bones develop. It results in the dog’s limbs being noticeably shorter. Other symptoms may be bowed forearms, irregular toes and problems with the hip joint.
• Affected breeds: Norwegian Elkhound

Skeletal Dysplasia 2 (SD2)

• SD2 is a type of dwarfism that causes long bones to stop growing before they are fully developed. It results in shortened limbs, with the front limbs being more affected. This type of dwarfism doesn’t’ affect the torso’s length or depth. Shortened stature is the only clinical sign of this condition.
• Affected Breeds: Australian Labradoodle, Labrador Retriever

Pituitary Dwarfism (DP-Lhx3)

• This is a genetic condition resulting in a lack of growth hormone. It’s called Pituitary Dwarfism as the hormone is produced by the Pituitary gland. This condition isn’t noticeable at birth, but the affected puppies won’t grow correctly and can die young. Affected dogs will appear puppy-like due to their appearance and will retain their puppy coat but can develop hair loss and have issues with tooth development.
• Affected Breeds: Tibetan Terrier

Osteochondro-dysplasia (OC)

• OC is a severe form of dwarfism resulting from abnormal bone and cartilage development. Signs show in puppies from 3 weeks old and affect growth and movement. Affected puppies are often euthanised due to severe joint stiffness. Although the stiffness lessens as the dog ages, their mobility may still be restricted due to the physical abnormalities. As they reach adulthood they have an increased risk of osteoarthritis.
• Affected Breeds: Miniature Poodle, Toy Poodle.

Eye Conditions

PRA

PRA occurs when retinal cells that receive light and translate it into vision degenerate and die. This condition affects both rods and cones, leading to night blindness and eventually complete blindness. The onset varies by breed, typically becoming noticeable from around 3 years of age. PRA results from various genetic mutations found in different breeds.

There are three main forms of PRA:

• Generalised PRA affects the entire retina.
• Retinal pigment epithelial dystrophy affects the outer retina layer.
• Sudden acquired retinal degeneration syndrome (SARDS) causes sudden, irreversible blindness

Glaucoma is a condition in which the pressure in the eyeball increases due to a lack of proper drainage within the eyeball. This then affects the optic nerve, and eye tissues and results in vision loss and or blindness.

There are different classifications of Glaucoma:

• Primary open-angle glaucoma (POAG)
• Primary closed angle glaucoma (PCAG)
• Congenital glaucoma
• Secondary glaucoma

Primary glaucoma is the most common in affected dogs and is broken down into open-angled or closed-angled – POAG or PCAG. The angle refers to the structure in the eye – iridocorneal angle which allows fluid to drain from the eye. In PCAG the angle is closed affecting the amount of fluid that can drain away from the eye. POAG the angle is open but other factors can affect the eye drainage.  PCAG is the more common of the two, but both conditions have hereditary components meaning testing is important for prevention through pre-breeding screening.

Other types of glaucoma that affect dogs are Congenital glaucoma (present from birth)and Secondary glaucoma (develops due to other eye diseases, such as cataracts or cancer) but these conditions are less common.

Dogs affected by Glaucoma tend to become actively affected mid to later life but can be affected earlier. How quickly the condition progresses depends on the type of glaucoma and can progress over years or months.

Types of Glaucoma and the breeds they affect:

• POAG/PLL – Shar Pei
• POAG – Petit Basset Griffon Vendeen, Basset Hound, Norwegian Elkhound, Beagle, Shar Pei
• POAG-2 – Norwegian Elkhound
• POAG-3 – Basset Hound
• POAG-5 – Petit Basset Griffon Vendeen
• PCAG – Italian Greyhound

Primary Lens luxation (PLL)

PLL affects the zonular fibres which support the lens in the eye, when these break down or disintegrate the lens moves into the wrong position within the eye. If the lens goes into the anterior chamber of the eye, it will quickly result in glaucoma and loss of vision. This condition is well-known in various breeds and is painful and blinding. Signs of PLL include redding of the eye, glaucoma and loss of vision. It can be detectable at 20 months of age, but complete lens luxation usually occurs at 3-8 years old.

• Affected Breeds: Chinese Crested Dog, Jack Russell Terrier, Lancashire Heeler, Miniature Bull Terrier, Parson Russell Terrier, Sealyham Terrier, Tibetan Terrier, Welsh Terrier, Hungarian Pumi, Italian Greyhound, Portuguese Podengo, Smooth Fox Terrier, Wire Fox Terrier, Pug

Canine Multi-Focal Retinopathy

CMR is a condition that affects the retina, changes can be noticed around 4 months of age. Small light-coloured lesions appear on the retina where it is detaching. The changes in the eye are slow and often stop by one year old. The condition doesn’t lead to blindness. In some cases, the lesions appear to heal as the dog ages, but vision loss is often reported. It is diagnosed through an eye examination. There are two types CMR1 and CMR2.

• CMR1 Affected Breeds: English Mastiffs, Bullmastiffs, Great Pyrenees, Australian Shepherds, Miniature American Shepherds, Boerboel, American Bulldogs, Bulldogs, French Bulldog, Cane Corso, Dogue de Bordeaux
• CMR2 Coton De Tulear, English Mastiffs, Bullmastiffs, Great Pyrenees

Microphthalmia (RBP4)

This disease affects the soft-coated wheaten terrier, where affected puppies are born with particularly small eyes and bodily defects. The result is the dogs have incurable blindness. The affected gene is the RBP4 gene which causes a vitamin A deficiency during pregnancy meaning the mother’s vitamin A did not reach the puppies. Puppies with two copies of the gene will only be affected if the mother has two copies of the RBP4 gene. If the mother only has one copy (a carrier) puppies that end up with two copies of the gene are unlikely to develop the gene.

• Affected Breeds: Soft-Coated Wheaten Terrier.

Collie eye anomaly/Choroidal hypoplasia (CEA/CH)

CEA/CH is the abnormal development of the choroid (a layer of tissue under the retina). This can be diagnosed early as it doesn’t develop properly at the start of the dog’s life. The presentation of the condition varies greatly between dog breeds. Most affected dogs only suffer a mild form of the condition; however, the disease can only be diagnosed through an eye examination. In mild cases the dog’s vision is normal throughout its life, unfortunately, any offspring from a mildly affected dog can be seriously affected by this condition which can result in vision loss.

• Affected breeds: Border Collie, Lancashire Heeler, Nova Scotia Duck Tolling retriever, Rough Collie, Shetland sheepdog, smooth collie, Australian shepherd, bearded collie, Miniature American shepherd.

Macular corneal dystrophy (MCD)

MCD causes cloudy eyes from an accumulation of glycosaminoglycans (carbohydrates) in the corneas. This disease is progressive but not painful, affected dogs will suffer from vision loss. It primarily affects middle-aged dogs.

• Affected Breeds: Australian Labrador, Labrador Retriever

Stargardt disease (STGD)

STGD is a retinal degenerative disease which leads to visual impairment and blindness. Its classified by the degeneration of both the rod and cone light receptors in the retina. These cells are vital for vision in bright and dim light. Affected dogs will present with the condition by 10 years old. Dilated pupils and decrease light response are visual symptoms.

• Affected Breeds: Labrador Retriever

Hereditary

Muco-polysaccharidosis type IIIB (MPSIIIB)

This condition effects the bodies’ ability to break down large sugar molecules, when there is build-up of this it can lead to cell function disruption. Particularly affecting the brains’ function. Signs show when the dog is 2-4 years old and affects the cerebellum (part of the brain that controls movement), the symptoms including tremors, difficulty balancing, walking and struggling on or around obstacles such as stairs.

• Affected Breeds: Schipperke

Imerslun-Gräsbeck syndrome/cobalamin malabsorption (IGS)

This condition results in vitamin B12 not being properly absorbed in the small intestine. B12 is vital for normal cell growth and works in conjunction with iron and folic acid to ensure the nervous system functions properly. It usually appears early in a dog’s life, presenting with a loss of appetite and lack of energy. Puppies with the disorder will struggle to grow normally. Affected dogs can also develop anaemia (reduced numbers of red blood cells), which will cause puppies to become weak and less able to exercise.

• Affected Dogs: Beagle, Border Collie, Australian Shepherd, Miniature American Shepherd.

Multidrug Resistance gene 1 (MDR1)

This inherited condition causes affected dogs to be sensitive to certain drugs such as ivermectin (an anti-parasitic) and loperamide (an opioid used to treat diarrhoea). In unaffected dogs, the blood-brain barrier protects brain cells from various drugs and toxins. There is a protein called P-glycoprotein that pumps drugs and toxins from the cerebrospinal fluid (the fluid that circulates around the brain and spine) back into the blood circulation. The MDR1 mutation results in this protein being inactive, which allows drugs and toxins to remain within the cerebrospinal fluid and potentially suppress brain activity. Dogs affected by this mutation that are exposed to these drugs may require extended veterinary care and, in severe cases, may face fatal outcomes.

• Affected Dogs: Australian Shepherd, Miniature American Shepherd, Border Collie, Rough collie, Shetland sheepdog, Smooth Collie, White Swiss Shepherd

Congenital Hypothyroidism with Goiter (CHG)

This condition prevents the dog’s body from properly producing thyroid hormones which a vital for development and growing. From 2 weeks a delay in growth can be noticed where unaffected puppies would have a growth spurt. Affected puppies may also suffer from fits or die at a very young age. Carefully nursed puppies may have a delayed start with their eyes and ears opening later, whilst hearing and brain development is affected. The thyroid can become enlarged and will present as swelling on the throat, this is known as goiter. Puppies that survive the early parts of their lives may suffer from irreversible dwarfism.

• Affected Breeds: Spanish water dog

Improper Coat (IC13)

IC13 is a gene variation that changes the dogs fur from the expected texture for the breed. For example a wire haired dog having straight fur. It can also affect or influence expected traits such has having eyebrows or a mustache. For some breeds/crosses having the IC gene variation seems to be associated with dogs prone to shedding.

• Affected Breeds: Portuguese Water Dog

Late onset ataxia (LOA)

LOA is a worsening level of coordination and loss of balance, which makes movement difficult. Affected dogs tend to present the disorder from 6 to 12 months of age. Additional signs of the condition are changes in the way the dog walks, such as weaving back legs and difficulty balancing. The disease is caused by the CAPN1 gene and requires a dog to have two copies of this to be affected. Dogs with one copy of CAPN1 won’t be affected but will be carriers and can pass it onto offspring.

• Affected Breeds: Australian Terrier, Jack Russell Terrier and Parson Russell Terrier.

Primary Cillary Dyskinesia (PCD)

PCD is like cystic fibrosis in humans. It’s the interference of clearing mucus from the airways which causes chronic inflammation in the nasal cavities, windpipes and lower airways. It causes regular infections for the dog due to the obstruction of fluid moving through the airways. This disorder also renders male dogs sterile as it causes sperm to be immobile. The condition presents with sneezing, nasal discharge, coughing and chronic bronchitis from the upper and lower respiratory infections. Other effects can be hydrocephalus (increase of fluid around the brain) and the infertility in males.

• Affected Breeds: Old English Sheepdog.

Cleft Lip/Palate and Syndactyly (CLPS)

A cleft palate is an opening in the room of the mouth where there two sides of the roof of the mouth failed to come together during embryonic development. It leaves an opening between the mouth and the nasal cavities. Symptoms that result from it are a runny nose, coughing, aspiration pneumonia, respiratory difficulty, difficulty nursing (for puppies), slow growth, weight loss, lack of appetite. Cleft palates can be inherited or have environmental effects such as vitamin deficiencies when in the embryonic stage. This disorder only affects a minority of the Toller population.

• Affected Breeds: Nova Scotia Duck Tolling Retriever

Juvenile Addison’s Disease (JADD)

Addison’s disease affects the adrenal glands, where the glands stop producing hormones used to control sodium and potassium levels in the blood. Signs usually start at 5 months old, and the dog will be tired, weak, and off their food with vomiting and diarrhoea. For a dog to be at risk, they require two copies of the mutated condition. As the disease is thought to have environmental and genetic influences, it means having the affected genes doesn’t guarantee the risk of having the disease the same as not having the affected genes doesn’t mean the dog won’t become affected. Current research shows 75% of dogs with two copies of the gene develop the condition.

• Affected Breeds: Nova Scotia Duck Tolling Retriever

Hereditary cerebellar ataxia (HCA)

HCA affected a dog’s ability to move. Signs can start from 12 weeks of age and progress as the dog ages. Affected dogs are often put down due to concerns about their quality of life. Symptoms are uncoordinated movement and head tremors.

• Affected Breeds: Norwegian Buhund

Lafora’s Disease

Lafora’s disease is a form of epilepsy that develops from a faulty enzyme. The enzyme should break down carbohydrates, but in affected dogs, a toxic starch material builds up in the cells, particularly nervous, liver and muscle tissues. This results in the dog rapid shuddering or jerking, which can be caused by loud noise, flickering lights or sudden movements. Dogs typically show signs around 5-7 years of age, and it progresses over time. Other neurological problems tend to develop, such as loss of control of movement, blindness, and dementia.

• Affected Breeds: Miniature Wire-Haired Dachshund, Basset Hound, Beagle, Chihuahua

Laryngeal Paralysis

LP is a breathing disorder usually found in Bull Terriers. It presents with difficulty breathing, especially when exercising. In severe cases, it can cause suffocation, leading to death. Larynx Paralysis may require surgery to relieve any breathing problems. Affected dogs may be less interested in exercising, have a high-pitched, noisy breathing sound, vocal impairments, difficulty breathing and collapsing. For Bull Terriers and Miniature Bull Terriers, a genetic variant has been found as a risk factor for early-onset LP. Dogs with two copies of the gene are 23 times more likely to develop the disorder. Therefore, any dog that carries one copy of the gene should only be bred to dogs clear of the condition to avoid producing affected puppies

• Affected Breeds: Bull Terrier, Miniature Bull Terrier.

Glycogen storage disease II (GSDII)

GSDII is a condition where the enzyme glucose-6-phosphatase, a vital part of glucose production is deficient. In affected dogs this leads to chronic low blood sugar levels, liver damage and early death. Dogs present with weakness, chronic low blood sugar, collapse, lethargy, and liver anorexia. Its present from birth. With type 2 dogs will also vomit frequently, have progressive muscle weakness poor body condition, and cardiac enlargement. Affected Dogs don’t tend to live past 2 years old.

• Affected Breeds: Finnish Lapphund, Lapponian Herder, Maltese, Swedish Lapphund.

Amelogenesis Imperfecta/Familial Enamel Hypoplasia (AI/FEH)

Affected dogs cannot produce regular amounts of tooth enamel to fully cover their teeth. Enamel is the hard protective surface of the tooth that prevents tooth decay. These dogs will have teeth that aren’t equally covered in enamel, and the teeth may also be rough and discoloured. The teeth may also be smaller and have larger gaps between them compared to unaffected dogs.

• Affected Breeds: Samoyed, West Highland White Terrier, Italian Greyhound, Japanese Akita Inu

Dental hypomineralisation / Raine’s Syndrome (Raine’s synd)

This condition is where a dog’s teeth experience excessive wear, resulting in tooth extraction. The affected teeth have a light brown discolouration in the enamel and appear dull, worn and cracked. Signs are usually noticed after the dog has all its permanent teeth. This condition is considered rare.

• Affected Breeds: Border Collie

Pyruvate Dehydrogenase phosphates (PDP-1)

PDP1 is a metabolic disorder. The enzyme pyruvate dehydrogenase phosphatase 1 (PDP1) is essential for cell metabolization – converting food to energy for cells. It presents with exercise intolerance and post exercise collapse as well as possible neurological signs.

• Affected Breeds: Clumber Spaniel, Sussex Spaniel

Acute Respiratory Distress Syndrome (ARDS)

ADRS is defined by sudden respiratory failure from fluid accumulation and severe inflammation of the lungs. It’s a life-threatening condition with a mortality rate of nearly 100%. This occurs following an episode that causes the dog to go into shock, such as a traumatic injury. ADRS is an underlying medical condition. It is triggered after a traumatic event, which allows blood, fluid and tissue to cross the lung barrier into the alveoli (air cells in the lungs), resulting in lung collapse. Once the alveoli are compromised, the dog’s breathing will become laboured. Symptoms include struggling to breathe, coughing, discharge from the nostrils, fever and blue discolouration of the skin. ARDS is a medical emergency requiring immediate veterinary treatment.

• Affected Breeds: Dalmatian

Copper toxicosis (COMMD1)

CT leads to the build-up of dietary copper in the liver, causing illness and death. The disease doesn’t show any symptoms in the early stages. Clinical signs are usually related to the liver, such as weight loss, anorexia, depression, vomiting, weakness, lethargy and dehydration. As the disorder progresses, symptoms can include bruising and blood in the stool. Without treatment, the dog will develop liver disease and die, usually between 3-7 years of age. CT is caused by the COMMD1 gene, whilst the mutation is a definite cause of the disease, there’s a belief that there are other genetic causes that aren’t yet identified.

• Affected Breeds: Bedlington Terrier.

Musladin-Lueke Syndrome (MLS)

MLS affects the development and structure of the connective tissue. This affects multiple organs and structures, including the bones, heart, skin and muscle.  The disease is defined by short toes on the front feet (sometimes all four feet), high-set creased ears on a flat skull with extra cartilage in them, slant, narrow eyes and very thick, tight skin with little scruff. Affected puppies are small in size with a stiff gait. Not all affected puppies will show these signs. The effect of the short outer toes means the dogs walk like ballerinas on their middle toes. They have a very good social temperament, although they have been reported to develop seizures. Some dogs can live normal lifespans as the condition stabilises as they mature, but they will remain small. Often, they die young as a result of problems associated with the disease. This disease is unique to Beagles.

• Affected Breeds: Beagle.