Lafora epilepsy genetic test is accredited by the Czech Accreditation Institute in compliance with ISO17025.
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.
It has been identified the NHLRC1-gene responsible for Lafora´s epilepsy in beagles und miniature wire-haired dachshunds. In December 2018, the same mutation was also found in chihuahuas. The gene dysfunction leads to aggregation and accumulation of polysaccharides and formation of glycogen particles (named Lafora bodies). The NHLRC1-gene encodes E3-ubiquitin ligase (malin) that controls laforin. Simply, the NHLRC1-gene takes part in protection of tissue against carbohydrate accumulation. The protective power is lost due to this mutation. The Lafora bodies are gradually growing in the central nervous system where they have neurotoxic effect. Besides the brain tissue the Lafora bodies are found in muscles, skin, liver and heart. Lafora disease is actually a glycogen metabolism disorder that demonstrates itself as progressive myoclonus epilepsy.
In NHLRC1 gene, unstable 12-mer expansion can ocuure (twelve-nucleotide sequence repeated several times). A healthy dog has one or two 12-mer in the gene, and can carry following combination:
In variant allele, number of repeating 12-mers may vary, the usual number of repeats is 19-26. The variant allele is called P. Dogs affected by Lafora's epilepsy have P/P genotype. Dog carriers of Lafora's epilepsy may have N2/P or N3/P genotypes.
Genetic testing that enables to determine the dog´s genotype is generally recommended. It can help the breeder to select potential breeding pair to ensure that the risk of producing affected puppies is very low and this disease will be gradually eliminated from the breed.
Mutation that causes Lafroa epilepsy is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive /negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers).