Why breathing problems aren't always due to a flat face

Analysis by Dr. Karen Shaw Becker

dog breathing problems

Story at-a-glance -

  • New research has uncovered a gene mutation associated with breathing difficulties in certain flat-faced dog breeds as well as, surprisingly, the Norwich Terrier
  • The presence of this gene mutation suggests breathing difficulties in certain brachycephalic breeds may be attributable to more than just the structure of their muzzles and skulls
  • The ADAMTS3 gene variant has also been associated in past studies with edema, which may play a role in the swollen respiratory tissues seen in dogs with upper airway syndrome and brachycephalic obstructive airway syndrome
  • The results of this study may at some point result in a genetic test for use by dog breeders as well as veterinarians

Scientists from the U.K., Switzerland and the U.S. have discovered a new gene mutation associated with breathing difficulties in certain dog breeds — including, surprisingly, the Norwich Terrier. The researchers published their study results recently in the journal PLOS Genetics.1

Their findings suggest that upper airway syndrome (often called brachycephalic respiratory syndrome, or brachycephalic obstructive airway syndrome/BOAS in dogs with flat faces) can be caused by factors other than the short muzzles and skull conformation of brachycephalic breeds such as the Pug and Bulldog.

Unlike brachy breeds, Norwich Terriers are “mesocephalic,” meaning their heads are not particularly long or short from front to back. (Dogs with longer skulls, such as the Greyhound and Afghan Hound, are “dolichocephalic” breeds.) The Norwich Terrier is predisposed to upper airway syndrome (UAS), which is why the research team went looking for a potential genetic influence. From the study:

“Respiratory diseases are prevalent across dog breeds, particularly in brachycephalic breeds such as the Bulldog and French Bulldog. The flat facial conformation of these breeds has long been assumed to be the major predisposing factor; however, the underlying genetics of their respiratory condition has never been elucidated.

We became interested in the Norwich Terrier, a breed presenting with many of the same respiratory disease symptoms as the Bulldog. A distinction, however, is that the Norwich Terrier is not considered to be a brachycephalic breed and so presented an opportunity to dissociate respiratory disease from head conformation.”2

Newly discovered gene mutation suggests breathing difficulties in certain brachycephalic breeds have more than one root cause

The research team, led by the University of Edinburgh's Royal (Dick) School of Veterinary Studies, examined the airways of more than 400 Norwich Terriers — about two-thirds of which showed mild to severe signs of UAS3 — and performed a genome-wide association study looking for genes linked to UAS. Their analysis revealed a mutation in the ADAMTS3 gene.

Next, to find out if other dog breeds carried the mutation, the researchers screened 1,300 dogs across 114 breeds, including many brachys diagnosed with BOAS. As it turns out, the genetic variance wasn’t as common as the team expected it would be. They only found the mutation in a few breeds — the Bulldog, French Bulldog, Norwich Terrier — and to a lesser degree, in some Staffordshire Terriers.

Around 80% of the Bulldogs had two copies of the ADAMTS3 mutation. Among French bulldogs, 3% had two copies and another 17% carried one copy. One of the unanswered questions from the study is whether one copy of the mutation is enough to increase disease risk, or if it takes two copies.

“We also looked at Pugs and other [brachycephalic] breeds at risk of developing BOAS, and in those dogs, we did not find the mutation that we isolated in Norwich Terriers, even though they do get obstructive airway syndrome,” study author Jeffrey Schoenebeck, Ph.D., told D-brief. “This tells us that we found something that has nothing to do with skull shape.”4

The researchers acknowledge there’s still a lot they don’t know about this genetic mutation and how it contributes to a dog’s risk of breathing difficulties — especially in the case of brachycephalic breeds.

“Norwich Terriers and French Bulldogs are genetically different, so we can’t automatically assume that this mutation is going to behave the same way in the genetic context of a French Bulldog,” says Schoenebeck. “My gut tells me it’s probably bad news for a dog with a flat face to also have this other thing, but we don’t have the data in hand yet.”

Needless to say, outside the newly discovered gene mutation, it wouldn’t seem Norwich Terriers and Bulldog breeds have much in common.

“It does bug me,” says Schoenebeck. “I want to understand why it’s concentrated particularly in the bulldog, French bulldog and Norwich terrier. We just don’t know what it is just yet.”

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Gene variant may also contribute to swollen respiratory tissues in dogs with airway syndrome

If you’re wondering what it’s like for dogs with obstructed airways to breathe, veterinarians often compare it to spending your life breathing through a straw.

Dogs who develop the problem “… may have nostrils and windpipes that are narrow, and soft palates that are cramped into a too-small snout,” according to D-brief. “Tissue sacks in the throat also can invert from hard breathing, blocking airways even more. Dogs with this breathing condition also tend to have respiratory tissues that are more prone to swelling — which could be how the ADAMTS3 gene plays a role.”5

Interestingly, past studies have linked mutations in ADAMTS3 to edema (fluid retention). Dogs who need corrective airway surgery and also carry the gene mutation may be at increased risk, which is obviously an important consideration. According to Schoenebeck, complications occur in about 25% of cases, and around 5% of dogs don’t survive those complications.

“Largely these surgeries go really well, but there are cases where the dog really crashes and doesn’t recover well from its surgery … are there complications in its recovery because its tissue tends to swell?”, he explains. “I hope [our study] opens up new lines of research.”

A genetic test may be on the horizon

"We conclude that there are additional genetic risk factors, that if inherited, will likely lead to airway disease in dogs regardless of their face shape," states Schoenebeck. "The challenge ahead is to integrate these ideas and implement sensible breeding practices and treatments that consider various health risks including those presented by the mutation of ADAMTS3."6

If a test for the ADAMTS3 mutation is developed, breeders can use it to avoid breeding individual dogs who carry the gene, and veterinarians can also use it to identify dogs at risk of UAS, especially in light of the fact that swelling of the airways after surgery is a common, life-threatening post-operative complication.

Hopefully this will become another genetic marker ethical breeders can use to improve the gene pools of future generations of dogs. If you love brachycephalic breeds and are contemplating buying one (remember, there are dozens of purebred rescues for every breed) it’s important to partner with a reputable breeder who practices reparative conformation; in this case, breeding for adequate snout length that allows for normal respiration.