Truffle hound helps root out childhood epilepsy gene

The Lagotta Romagnola:fit for function?

The first-ever gene for idiopathic epilepsy in dogs has been found by Professor Hannes Lohi  at the University of Helsinki, heading an international team of scientists.

The mutation - in a gene called LGI2 - appears to be unique to the Lagotta Romagnolo, the appealingly-shaggy Italian breed known for its excellent truffle-hunting skills.  The Lagotta suffers a form of juvenile epilepsy marked by seizures causing tremor, trembling, shaking and wheezing which, typically, set in at around four weeks of age and last for up to two months before stopping completely. The researchers believe the same gene could be responsible for a similar type of epilepsy found in children.

"Remission is so reliable that the epilepsy is considered by many breeders as an unfortunate particularity of the breed and often disregarded" write the authors of a new paper published online in PloS Genetics.

This is indeed the case. Here's what  the Lagotta Romagnolo Club of GB  has to say about the condition (known in the breed as BFJE - Benign Familial Juvenile Epilepsy - although not on the Club website which has had no health updates since, er, 2003. There, they're still referring to it as a "cerebella anomaly").

"So do Members have to worry about their dogs developing this anomaly? ABSOLUTELY NOT," they insist. "It is only when breeding that the Anomaly may be produced.  Furthermore if we followed (and by we I mean everyone in the world breeding Lagotto) the usual advice in eliminating an inherited disease – namely do not breed from a suspected carrier’s descendents, siblings or parents Lagotto would cease to exist as a breed."

A little shocking but probably true. As the researchers report:  "The popularity of the breed fluctuated with the truffle industry and in the early 1970s underwent a strong genetic bottleneck to near extinction, when a group of dog lovers decided to save it."

No surprise, then, that the researchers have found that one in three Lagottos carry the mutation, which is an autosomal recessive. This means that a dog usually has to inherit two copies of it (one from each parent) in order to be affected.  However, the researchers also found that of the 28 affected dogs in the study for which they had DNA samples, two of them (7%) had only one copy of the mutation. This means that carriers can occasionally suffer, too.

In truth, an epilepsy that invariably resolves by the age of four months is not the most serious of problems  - although the researchers still hope that breeders will avail themselves of the new DNA test for Lagottos developed by the Finnish team and offered through Lohi's company Genoscoper Oy (Ltd) for €85.

Sadly, there are other neurological problems in the breed: "The study revealed another form of epilepsy in the breed, unconnected with this mutation and with an age of onset in adulthood. In addition, the breed has a progressive juvenile ataxia (lack of motor coordination) with similar onset and symptoms to juvenile epilepsy except that it does not remit -- ataxic puppies have to be euthanized usually by the first year of life. More samples are needed for both adult-onset epilepsy and ataxia to enable us to investigate their genetics further," says a primary author of the study, Eija Seppälä, PhD.

Epilepsy is the most common neurological disease in children - occuring in 1 in 200 children aged between two and 10 years old. 

It is also the most common neurological disease in dogs - in some breeds 10 times more common than it is in humans.

Meanwhile, two other new canine epilepsy studies report interesting findings - the first that neutered male dogs may be more likely to have epilepsy; the second that giving epileptic dogs essential fatty acids (long recommended by some as an alternative treatment for epilepsy in humans and dogs) made no difference whatsoever.

Characteristics of epileptic episodes in UK dog breeds: an epidimiological approach (A Mount et all, Vet Record, 2011) looked at a cohort of 1260 epileptic dogs from 78 known breeds as well as a group of crossbred dogs.  The researchers found that epilepsy was more common in male than female dogs. This is in line with previous studies but, in a new finding, the researchers found some evidence that neutering may be a risk factor for epilepsy in male dogs. Previously, neutering has been believed to reduce seizure in epileptic dogs.

The authors urge caution re over-interpreting the results as the data come from a laboratory-based recruitment as opposed to a clinical study - but it is nevertheless interesting, especially with the growing awareness that there are health costs as well as benefits to neutering.

The researchers found also that just four pedigree dog breeds - and crossbreeds as a group - accounted for more than half of the cases of epilepsy in their study:

Crossbreeds - 20.5%
Labrador Retriever - 11%
Border Collie - 10.5%
German Shepherd - 6.5%
Staffordshire Bull Terrier - 5.2%

In a separate study (Effects of essential fatty acid supplementation in dogs with idiopathic epilepsy: A clinical trial, Helen Matthews et al, Veterinary Journal, article in-press) researchers found that giving dogs Omega 3 oil - recommended by many as a natural/supplemental treatment for epilepsy - did not help.

"The effects of essential fatty acid supplementation (EFA) on the control of idiopathic epilepsy in dogs were investigated in a blinded, placebo-controlled trial," write the authors. " Fifteen dogs were treated with triple purified Ω-3 oil containing 400 mg eicosapentaenoic acid, 250 mg docosahexaenoic acid and 22 mg vitamin E per 1.5 mL at a dose of 1.5 mL/10 kg once daily for 12 weeks, followed by a 12 week placebo period of supplementation with olive oil. Owners recorded seizure frequency and severity and any adverse events. EFA supplementation did not reduce seizure frequency or severity in dogs with idiopathic epilepsy."

There was one exception though, according to co-author Barbara Skelly from the University of Cambridge Vet School. "Our results showed that in the majority of dogs there was no appreciable difference in the response to both oils but one dog did appear to show a dramatic response and therefore a larger scale investigation is probably merited."

That's probably enough to reassure all the proponents of EFAs....