Testing of dogs: Juvenile Epilepsy

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Juvenile Epilepsy in Lagotto Romagnolo breeds

Epileptic syndromes are expression of exaggerated activity of cerebral neurons. The idiopathic generalized epilepsies are genetically determined and for some of them, the responsible causative molecular genetic defect has been already identified. Characteristic for them is the relation of individual types of epilepsy to a specific age.

Epilepsy is a disease that affects people, dogs and other mammals. The genetically determined juvenile epilepsies belong to the most common neurological diseases in children between 2 to 10 years of age. They occur in 0.5% of population and are characterized by spontaneous remission during the child growth. They are closely connected to the second stage of postnatal brain development.

The postnatal brain development in mammals can be divided in 3 stages:

  1. From birth to 2 years of age in humans; from birth to 1 week of age in mice; from birth to 2 months of age in dogs; Approximately one quadrillion of synapses are formed in this stage in humans
  2. From 2 to 10 years of age in humans; from 7 days to 17 days of age in mice; from 2 to 4 months of age in dogs; In humans, this stage is characterized by massive removal of unneeded synapses (almost half of the original synapses)
  3. The reminder of life; The number of synapses remains stable

In 2011, Seppälä at al. described the mutation c.1552 A>T in LGI2-gene leading to the creation of  premature stop-codon in exon 8 that is responsible for the juvenile epilepsy type affecting the Lagotto Romagnolo breed. The LGI2-gene is expressed in the second stage of post-natal period of brain development and acts on the group of neuronal receptors of the ADAM family which function is synapse remodelling. The LGI2 truncation prevents secretion and interaction with ADAM receptors.

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In the Lagotto Romagnolo canine breed, the epileptic syndromes occur at 5 to 9 weeks of age (equivalent to 2 years of age in humans). The seizures manifest by tremor of the entire body sometimes connected with short loss of consciousness. The puppies with most severe seizures show also signs of neurological disease including generalized ataxia and hyperthermia. The epileptic seizures resolve spontaneously by 8 to 13 weeks of age (in humans by 8 years of age).  The remission of seizures is characteristic for this type of epilepsy and therefore this disease is considered only as an unhappy disorder by many breeders that disappear at higher age of the puppy to a great relief of breeders. However, the life quality of the puppy should be taken into account. By timely testing of the parent dogs producing puppies suffering from unpleasant epileptic seizures at a very early age can be avoided.

Juvenile Epilepsy in Lagotto Romagnolo is a recessively inherited disease. The disease develops in dogs which inherit the mutated gene from each parent.  These dogs are designated as P/P (positive/positive). The carriers of the mutated gene are designated as N/P (negative/positive). The carriers inherited the mutated gene from one parent only and are without clinical signs. However, they pass the disease on to their offspring.  When mating two heterozygotes (N/P), there will be theoretically 25% of the offspring healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will be affected by Juvenile Epilepsy.  Mating one healthy dog (N/N) with a carrier of this mutation (N/P) will theoretically produce 50% carriers and 50% healthy offspring.  If a carrier (N/P) is mated with an affected dog (P/P), there will be theoretically 50% affected dogs and 50% carriers.

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Reference:

Seppälä EH1, Jokinen TS, Fukata M, Fukata Y, Webster MT, Karlsson EK, Kilpinen SK, Steffen F, Dietschi E, Leeb T, Eklund R, Zhao X, Rilstone JJ, Lindblad-Toh K, Minassian BA, Lohi H.: LGI2 truncation causes a remitting focal epilepsy in dogs; PLoS Genet. 2011 Jul;7(7):e1002194. doi: 10.1371/journal.pgen.1002194. Epub 2011 Jul 28.

Jokinen TS1, Metsähonkala L, Bergamasco L, Viitmaa R, Syrjä P, Lohi H, Snellman M, Jeserevics J, Cizinauskas S.: Benign familial juvenile epilepsy in Lagotto Romagnolo dogs; J Vet Intern Med. 2007 May-Jun;21(3):464-71.

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Usual turnaround time: 7 business days
1 test price: 54.00 $ without VAT