Laflora
This Disease is reported in Beagles, Miniature wire Haired Dachsunds, Bassets and People. It is caused by a defect in the gene EPM2A which codes for glycogen phosphatase laforin or the EPM2B gene coding for Ubiquitin E3 ligase malin. In dogs the defect is in the EPM2B gene and there is a massive expansion of the gene with multiple repeats of part of it. This leads to loss of function of the gene resulting in an excessive accumulation of glycogen with certain cells and this is converted into an insoluble substance called polyglucosan. Gradual precipitation of this in neurons is called Lafora Bodies –named for their appearance microscopically. This leads to a neurodegenerative disease initially showing myoclonus-twitching and jerking movements. These progress to tonic-clonic seizures.
Affected patients may show other signs such as transient blindness, visual hallucinations (sudden unexplained fear response), and photo-convulsions (flashing light or sunlight affects them). It is hard to diagnose in the live patient as bloods, urinalysis and CSF analysis is normal. EEG measurements may register spikes and some show abnormal EMG as well. MRI may show cortical atrophy as well. Most cases are diagnosed post mortem or can now be tested for DNA.
Treatment of this disease is hard as it is a cumulative problem. Some success has been found using the drug Leviteracetam to reduce myoclonic jerks and a low carbohydrate diet to reduce glycogen production. Doggles may be used in patients with light sensitive clinical signs. Ultimately sadly most patients progress is poor and are euthanized due to worsening symptoms.
Neonatal cerebellar cortical degeneration (NCCD)
Is a hereditary disease that can affect Beagles puppies. Affected puppies start showing clinical signs at around three weeks of age. They are slower and less coordinated than their littermates, fall more often and are unable to regulate a normal gait. This disease has minimal progression but currently there is no cure. The clinical signs are due to damage in their cerebellum, which is the part of the nervous system that controls the movement and the equilibrium. Mutation Identified: In 2012 veterinary neurologists and scientists from the Kennel Club Genetics Centre at the Animal Health Trust identified the mutation for NCCD in the Beagle and made a DNA test available. The mutation is recessive, meaning only dogs that inherit two copies of the mutation are affected by NCCD; dogs with one copy (carriers) or no copies (clears) cannot develop NCCD although carriers will pass the mutation onto about half of their puppies if they reproduce. DNA Test: Beagle owners who use the NCCD DNA test will be sent results identifying their dog as belonging to one of three categories. In all cases the terms ‘normal’ and ‘mutation’ refer to the position in the DNA where the NCCD mutation is located; it is not possible to learn anything about any other region of DNA from the NCCD DNA test.
CLEAR: these dogs have two normal copies of DNA and will not develop NCCD as a result of the NCCD mutation. Please note; we cannot exclude the formal possibility they could develop a clinically similar but genetically different disorder due to other mutations that are not detected by this test.CARRIER: these dogs have one copy of the mutation and one normal copy of DNA. These dogs will not develop NCCD themselves as a result of the NCCD mutation but they will pass the mutation on to approximately 50% of their offspring.Please note; we cannot exclude the formal possibility they could develop a clinically similar but genetically different disorder due to other mutations that are not detected by this test. GENETICALLY AFFECTED: these dogs have two copies of the NCCD mutation and will be affected with NCCD.
Breeding Advice The NCCD mutation is recessive so both clear and carrier dogs can be safely bred with, provided at least one of the mating pair is clear of the mutation. Carriers should always be included in the first one to two generations that follow the launch of a DNA test for a recessive mutation, regardless of the frequency of the mutation, to give breeders the opportunity to capture desirable traits, such as breed type and temperament, before they start to select for dogs that are clear of the mutation. Elimination of the NCCD mutation from the breed should be the long-term goal, now that a DNA test for that mutation is available. But, providing all breeding dogs are tested for the mutation prior to mating, Beagle breeders should take their time and ensure that desirable traits are not eliminated along with the disease mutation and that the genetic diversity of the breed is reduce.
Musladin-Leuke Syndrome (previously Chinese Beagle Syndrome)
Those of you who follow International Beagle News may have heard of Chinese Beagle Syndrome or Musladin-Leuke Syndrome (MLS). The conditions are the same thing and MLS is the current correct name for this disorder. MLS is a genetic disorder, caused by a founder mutation (a gene mutation which has been dated to the foundation of the beagle population) which results in a beagle born with several defects characterised by short outer toes on the front and sometimes all four feet, high set creased ears on a flat skull with extra cartilage in them, slant narrowed eyes and very thick tight skin with little scruff. Such pups are small in stature with a very stiff gait BUT not all affected pups will show all these signs. The short toes make them walk like a ballerina on their middle toes. They have a very good gregarious temperament although many have been reported to develop seizures. There are some clear dogs that have conformational defects as above so we must be careful and not assume anything unless a dog has been DNA tested.This condition was always assumed by breeders here not to be present in the UK BUT it is and we need to find out how widespread it is and over a sensible period of years try to eliminate it. Since the news broke there have been several people who feel they may have seen it and reports of beagles in packs having it so it is likely as in other countries that we have had it unrecognised for some time. Since the UK beagle is based on packs it is possible the gene is present in many of the show beagles and may crop up at any time when two carrier parents are inadvertently mated together. The disease has been described in detail in a scientific paper and this describes the distribution as being seen in England (we take that to mean Europe since it has been described personally), Australia, America and Japan and is unique to beagles. It is likely to have originated as a single mutation at the point the beagle was being developed and population spread around the world so probably the end of the nineteenth century. It is first described in the literature in the 1970’s as being an incidence of 2-3% in the beagle population in Britain and Australia. There are human diseases, which are similar called “Stiff skin syndrome” and also Geleophysic dysplasia both of which are rare inherited disorders. MLS sufferers have a thick inelastic skin, and thick fibrous muscles with little flexion even under anaesthesia. This leads to the stiff gait and also the hard inflexible abdominal wall. The facial features are produced as the bone is very dense and the ears and skin thickened pulling back the skin and hence the slanted eyes. Further discussion of MLS can be found on the International web site www.salenko.co.uk/MLS. The only way to know which puppies are affected is to test, and there is a DNA test available from UC Davis in the USA. The gene causing the mutation is a recessive one so both parents need to be carriers to produce affected puppies. A recessive gene is one that is hidden (as opposed to a dominant gene which produces visible characteristics). For a discussion of genetics please see the web site. Testing is simple and inexpensive so lets not pretend this is not here but test if possible. The test has been developed in the USA when breeders spoke out and said they had the condition and got together with Dr Mark Neff to collect DNA and work out the hereditary pattern. We are fortunate that they spoke out and we can benefit from this.
Steroid Responsive Meningitis(SRM)
This condition is seen in other breeds of dog too but Beagles along with Bernese Mountain Dogs, Duck Tolling Retrievers and Springer Spaniels seem to be over-represented in the canine population. It is primarily a disease of the younger dog, most often being seen around 6-8months of age for the first time although it has been seen as young as 10 weeks and in dogs of up to 2 years. However there is a form in older dogs more often called Granulomatous Meningo-Encephalitis or GME. SRM is more likely to be treatable with GME sometimes being refractory to treatment and more likely to result in a dog that doesn’t respond well to treatment.
The cause of SRM is unknown at the moment. It is known to be an immune response but the trigger has not been identified. The immune response results in an intense inflammation of the blood vessels supplying the neurological system particularly the meninges (lining around the brain) and the cervical spinal cord (neck). The body is “attacking” its own cells and suppression of this is imperative in treatment.
The symptoms seen reflect the pain produced in the head and neck area and most commonly dogs present with a stiff gait, reluctance to eat and drink, lethargy and pyrexia (raised temperature). Beagles are very stoic and as such the owner may not be able to pinpoint initially exactly what is wrong just that the puppy is out of sorts. Often this is initially attributed to an injury since Beagles are generally lively and some affected dogs may cry out in pain. However the usual use of non-steroidal anti-inflammatories such as meloxicam and carprofen does not produce any improvement. There is no infectious cause so anti-biotics do not work either.
Diagnosis is most commonly based on symptoms and a spinal tap. Samples are taken under a General Anaesthetic from the fluid bathing the cervical spinal cord and they show typical changes of increased numbers of cells and protein. The recent use of the Magnetic Resonance Imaging technique (MRI) is also producing very useful information on the condition, giving an idea of the severity of the disease in an individual and helping to decide on the best treatment regime. Some dogs may have an apparently normal spinal tap but the MRI scans show abnormalities consistent with the inflammation within the brain. MRI scans have the advantage of being completely safe although expensive. The spinal tap although much cheaper runs a small risk of herniation of the hind brain into the spinal canal. This means the brain can move backwards into the space caused by removing some fluid causing pain and sometimes seizuring. Ideally both diagnostics should be carried out.
Initial treatment regimes are based on suppressing the immune response that has caused the problem. Steroids usually prednisolone at an immuno-suppressive dose are used and then the dose tapered down. The course is ideally carried on for a number of weeks with a slow tapering down and increasing the dose back up with any recurrence in symptoms. A short course of anti-biotics is usually given after the spinal tap. A new and very useful treatment is a drug known as cytarabine. More commonly used in chemotherapy this drug is proving a very effective treatment for SRM. It is an injection and initially given intravenously but can be given under the skin at a later stage. The side effects are uncommon and it can be given easily in consultations at the vet. It produces a quicker response and at the moment seems to be resulting in less relapses than using steroids alone.
Given that some breeds of dog are over represented in the population with SRM there is a possibility of a genetic predisposition that basically means the Beagle (and others) may have a hereditary problem that makes them more likely to develop the disease.
Factor VII Deficiency
Within the body is a biochemical pathway known as the clotting cascade. Whenever any tissue is injured the clotting cascade swings into action and prevents uncontrolled bleeding. This can be after bruising, cuts, trauma and any other tissue injury however minor. Each step is controlled by a different chemical reaction and or interaction and for these to work all the chemicals or interactions must be produced by the body-this is under genetic control. If any of the genes, which control production of the steps, are missing or defective the individual may have clotting problems. Thus a minor bruise or knock results in bleeding into the tissue and wounds may bleed for longer than normal.
Factor VII is one of the proteins involved in the clotting cascade and is found in the early stages. If a blood vessel wall is injured Factor VII may leak out and bind with Tissue Factor, which is found, stuck to the outside wall of the blood vessels. This binding triggers a series of chemical reactions leading to a clot forming and the leak plugged.
Deficiency of Factor VII can lead to mild to moderate bleeding, as the cascade doesn't progress properly. This deficiency is found in man as well as dogs and is inherited as a recessive disorder. Breeds known to be affected by this particular gene mutation are the Beagle, Deerhound, Airedale, Alaskan Klee Kai and Giant Schnauzer. There may be others as well.
A recessive disorder means that a dog needs to carry two copies of the mutant gene to be affected and have problems. The gene responsible for Factor VII deficiency was first properly identified in beagles in a research colony in the USA although it was known to be around before then. It has subsequently been found that the general beagle population around the world also carries this mutation and there are reports of beagles with bleeding disorders when they undergo surgery. It seems likely this gene is widespread as it often only produces a mild increase in clotting time, which goes unnoticed. So far several beagles around the world have been tested and the results support this. The gene test can be used to alert dog breeders to the status of their breeding stock and as a further tool to ensure they breed healthy dogs.
Factor VII is Vitamin K dependent and ingestion of anti coagulants such as warfarin reduces the livers ability to produce vitamin K. Warfarin and similar compounds are also the basis of many rat bait poisons. Many people will know of the risk of rat bait to dogs and how they can haemorrhage. A dog affected with Factor VII deficiency would be at high risk if it had ingested such a poison.
Unlike MLS, affected dogs should not be eliminated from the general population without careful consideration. Many affected dogs do not have severe bleeding problems and can be safely mated to a clear dog without producing affected puppies. When breeding the Beagle one must take lots of things into account. We are in a world now where DNA testing is advancing fast and this is another tool for breeders to use.
Diseases such as Steroid Responsive Meningitis, Epilepsy, Musladin-Lueke Syndrome and Hip Dysplasia are all currently discussed in the breed and we need to look at all aspects when breeding not just take a single test result and use it for our selection process.