Epilepsy is one of the most frequent chronic neurological diseases in dogs affecting approximately 5 % of all dogs. The Lafora’s disease is a type of hereditary epilepsy appearing in some breeds. For the first time it has been discovered in pedigree miniature wire-haired dachshunds. For example, in Great Britain the percentage of miniature wire-haired dachshunds affected by this autosomal recessive progressive disease exceeds 5%. Among other breeds suffering from this disease belong, for example, Basset Hounds, Miniature and Standard Poodles, Pointers, Welsh Corgis or Beagles. With regard to no relationship between some breeds affected by Lafera’s disease it seems that the mutation occurred repeatedly and was spread due to inbreeding.
Generally, the clinical signs appear at 5-6 years of age or later. They include mainly myoclonus/jerking (sudden involuntary muscle jerking or twitching typical for epilepsy) and the frequency of seizures increases over time and the uncontrolled jerking and twitching is followed by other neurological symptoms such as ataxia, twinkling, blindness or dementia. During seizures, the convulsions are commonly accompanied by muscle rigidity, vocal utterance, salivation, urination or loss of consciousness. The epileptic seizures can arise in spontaneous unpredictable fashion or can be induced by light flashes, sudden sounds or movements, particularly close to the dog’s head.
This form of epilepsy is incurable and fatal. The therapy is currently limited to treatment of seizures; suitable diet and medication help to keep the seizures under control.
Factor VII is a clotting factor synthesized in the liver that is necessary to initiate blood coagulation when vascular injury occurs. Factor VII deficiency is a mild to moderate inherited blood clotting disorder present in Beagle, Airedale, Alaskan Klee Kai, Giant Schnauzer and Scottish Deerhound breeds. It is inherited as an autosomal recessive, thus both females and males can be affected if they carry 2 copies of the defective gene but animals with only 1 copy are not affected.
Imerslund-Gräsbeck syndrome (IGS) is a disorder found in Beagles and Border Collies where dietary cobalamin (vitamin B12) is unable to be absorbed through the gut. Both breeds have independent mutations in the cubulin (CUBN) gene. The disease has an autosomal recessive mode of inheritance with both sexes being equally affected. Owners of IGS affected dogs often note a lack of appetite, failure to gain weight, lethargy and malaise that intensifies after eating. Clinically, anemia and excess urine protein is observed. Without chronic treatment, permanent brain and nervous system damage can occur. Dogs with one normal and one mutated IGS gene, carriers, are unaffected but breeding two carriers together would be predicted to produce 25% affected offspring and 50% carriers.
Musladin-Lueke Syndrome (MLS) is a genetic disease of the Beagle that affects the development and structure of connective tissue. It is multi-systemic, with involvement of multiple organs, including bone, heart, skin, and muscle. MLS is inherited as a recessive trait. Current evidence suggests that dogs that have two copies of the mutant gene are affected with MLS, though the severity of clinical signs can be variable. Dogs inheriting only one copy of the mutant gene can show subtle signs but do not appear to have health-related defects. To the best available knowledge, carriers cannot be identified based on their appearance.
The disorder stems from a single mutation that has been inherited through common descent, such that all affected Beagles share the gene from a common ancestor, perhaps dating back to the foundation stock of the breed. This mutation has been identified by Dr. Mark Neff at the Veterinary Genetics Laboratory, School of Veterinary Medicine, UC Davis.
Research is ongoing and there are still aspects of this disease that are continuing to be investigated such as the geographic distribution of the mutation among purebred Beagle bloodlines, and the variable nature of the disease.
Inherited neurological degenerative diseases are found in several mammalian species including humans, horses and dogs. Cerebellar cortical degeneration, also called cerebellar abiotrophy, is a disease characterized by ataxia (lack of coordination), broad based stance, loss of balance and intentional tremors. In different breeds of dogs, the onset is variable from neonatal to adult. In Beagles the condition is neonatal and onset is noticed at about 3 weeks of age as puppies begin to walk. The severity of the condition is variable among individuals but progression of clinical signs is minimal. Research identified an 8bp deletion in the Beta III Spectrin Gene (SPTBN2) associated with NCCD in Beagles.
Primary Open Angle Glaucoma (POAG) in the Beagle breed is an autosomal recessive disorder resulting from a mutation in the gene ADAMTS10. The mutation causes pressure in the eye to increase and, if untreated, nerve damage, vision loss, lens subluxation and blindness may result. Both sexes are equally affected and carriers for the mutation do not exhibit any effects. The mutation has an estimated frequency of 1% in the Beagle population.
Pyruvate kinase deficiency (PKDef) is an inherited hemolytic anemia caused by a defect in the enzyme pyruvate kinase. Loss of function of this enzyme results in premature death of red blood cells. Affected dogs do not have sufficient quantities of red blood cells to adequately supply the body with oxygen. Observable signs in affected dogs may include lack of energy, low exercise tolerance and fatigue in dogs that appear otherwise fit. Clinically, dogs with PKDef present with a severe anemia, increased iron levels, increased bone density, may have an enlarged spleen and liver as well as fibrous connective tissue replacement of bone marrow cells. Bone marrow and liver failure typically occur by 5 years of age. The disease is inherited as an autosomal recessive disorder thus both sexes are equally affected and two copies of the defective gene must be present for dogs to be affected. Carrier dogs, those with one defective and one normal copy, show no signs but have half the normal level of pyruvate kinase activity. Breeding two carriers is expected to produce 25% affected offspring and 50% carriers of the disease.
This is an autosomal recessive condition that affects Labradors, as well as several other related breeds. The condition is also seen in mixed breeds, mainly Labrador crosses. The condition is not common, although it is estimated up to 35% of the Labrador population (in the USA) may be carriers of the gene mutation that causes the disease (ie mutation of the dynamin-1 gene). Signs are usually first seen in young adults, between 6 months and 3 years of age. With vigorous exercise lasting 5-20 minutes, a loss of control becomes apparent in the hind limbs. Starting as a wobbly gait, the loss of control progresses to collapse, and sometimes dogs may seem confused. Occasional deaths have been reported, so it is important that exercise is stopped as soon as signs first appear. Excitement and high temperatures and/or humidity may exacerbate signs. There are sporadic reports of various supplements having some positive effect in a small number of dogs, as well as one report of sub-anticonvulsant doses of phenobarbitone being useful in some severely affected dogs; however there is currently no proven reliable cure or treatment for this disease. All affected animals should be withdrawn from work and should avoid situations involving excitement and/or stress.
Progressive retinal atrophy (PRA) is a collection of inherited diseases affecting the retina that cause blindness. Each breed exhibits a specific age of onset and pattern of inheritance, and the actual mechanism by which the retina loses function can vary. The result of almost all types of PRA is similar – generally an initial night blindness, with a slow deterioration of vision until the dog is completely blind. The age at which the dog becomes fully blind also varies, depending on the genetic disruption present and the breed. Affected eyes are not painful, unless complicated by a secondary problem, such as cataract or uveitis (inflammation due to a leaking cataract). Progressive retinal atrophy (PRA) has been classified in several different ways. The simplest of these is by age of onset. Early onset PRA occurs when the affected dog is night blind from birth, and generally is completely blind between 1 – 5 years of age. Late onset PRA is where the dog is night blind at some time over 1 year of age, and full blindness will occur at a somewhat later stage in life. Another is by the type of genetic abnormality causing the PRA. PRA may be inherited by recessive, dominant or sex-linked mechanisms in dogs. For many types of PRA in many breeds a DNA test is now available to allow for easy screening for the disease. Despite the complexity of the disease and its many forms, ultimately all forms have one thing in common – degeneration of the retina causing progressive loss of vision. DNA tests are not yet available for all affected breeds. And because breeds may also be prone to several forms of PRA (and not all may have a genetic test available) examination of the retina by a veterinary ophthalmologist remains a mainstay of the diagnostic testing regimen. In some breeds with a late onset PRA, serial eye examinations may be required before the signs of retinal degeneration become apparent. The electroretinogram (ERG) is a diagnostic test that the veterinary ophthalmologist may choose to use in some cases and is a very sensitive method of detecting loss of photoreceptor function. An ERG can be a very good screening test for puppies that may have an early onset form of PRA. Cone-rod dystrophy due to a CORD1variation (a gene mutation at RPGRIP1) is an autosomal recessive form of PRA that occurs in a number of breeds including some types of dachshund (smooth-haired, long-haired and wire-haired), English springer spaniels, and beagles. There is a DNA test for this type of PRA in all the above-mentioned breeds. Modifying genes that act on RPGRIP1 have been found, and are thought to affect when the disease becomes apparent (affecting the age of onset of clinical signs). In addition it is thought that there is some degree of variable penetrance seen with CORD1-PRA, which contributes to the wide variation in the clinical syndrome that is seen – for example it is known that the onset of clinical signs may occur between 2 and 10 years of age. Some cases have been documented of dogs with two copies of the CORD1-PRA mutation and no clinical signs of disease, indicating that indeed other factors contribute to disease expression. In cone-rod dystrophy1, cones degenerate first, followed by rods – this can be detected by the ERG, a specialised test of retinal function. This is called cone led degeneration. The cones are the receptors in the back of the eye that detect bright light and different colours. The rods are the receptors that detect dim light and produce night vision, so dogs with CORD1-PRA do not develop night blindness first as do most dogs with PRA. These dogs gradually lose all vision, but may initially have better vision in low light than in bright light. As with all dogs suffering from PRA, there is no cure. Dogs generally adapt quite well to blindness – especially when it develops gradually – as long as their surroundings remain familiar (e.g. furniture does not get rearranged, they do not move house etc). They should always be kept on a lead outside the yard, and care should be taken not to startle them. Balls containing bells (as an example) can be used as toys for mental stimulation.
Congenital stationary night blindness (CSNB) is a rare inherited eye disease affecting dogs. CSNB causes slowly progressive degeneration of the Retina, which is the part of the eye that collects visual information and communicates with the brain. Loss of night vision is first noticed in affected dogs as early as 5 weeks of age, while ophthalmologic changes are not visible until affected dogs are 2-3 years of age. Light brown patches form on the surface of the retina. These patches increase in size and coalesce over time until the entire retina is affected. Affected dogs may be reluctant to move in low light and over time, day vision is also lost.
Catalase deficiency (hypocatalasemia or acatalasia) is a rare autosomal recessive disorder that is caused by mutation in the gene responsible for the production of catalase, an anti-oxidative enzyme. Catalase enzymes are responsible for regulating the metabolism of hydrogen peroxide, one of many by-products generated during the respiration process during which molecular oxygen is transformed. Dogs with catalase deficiency are particularly sensitive to hydrogen peroxide’s oxidative stress, causing painful oral sores and altering other important metabolic processes.
Degenerative myelopathy is most commonly seen in the German Shepherd Dog, although other breeds are also predisposed, including the boxer, Cardigan and Pembroke Welsh Corgi, Siberian husky and the Rhodesian ridgeback. This disease is normally seen around middle age, and in general diagnosis can only be confirmed at post mortem examination. Breed surveys of some predisposed breeds indicate a fairly low occurrence rate, but most experts think this rate is actually much higher, due to the lack of post mortem follow up of the majority of suspected cases. Signs are due to the immune-mediated destruction of a part of the nerves in the spinal cord, leading to loss of these nerve fibres. The first sign is knuckling of the hind feet, and hind limb ataxia. Once the spinal cord damage progresses past this initial stage (termed proprioceptive deficits), the effectiveness (if any) of treatment is much diminished. Hence early diagnosis is vital. Following this initial stage, hind limb reflexes are affected, then weakness in the hind limbs develops, progressing to total paralysis. Once a dog shows these signs it will almost always respond poorly to therapy. Eventually destruction progresses from the middle of the spinal cord to the upper cord and brain stem, leading to forelimb weakness and eventually interference with the muscles of breathing, causing death. Most dogs are euthanised for humane reasons before this happens. Treatment is with specific supplements and drugs aimed at interfering with the immune destruction in the spinal cord, to slow further nerve damage. The effectiveness of this treatment is variable, but is only of benefit if started as early as possible. Once nerves are lost, they will not be replaced. Degenerative myelopathy cannot be cured. A DNA test is available for predisposed pure breeds to carry out screening of breeding animals