What Practitioners Should Know About the Genetics of Brachycephaly
World Small Animal Veterinary Association Congress Proceedings, 2018
Jerold S. Bell, DVM, Adjunct Professor of Clinical Genetics
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, N. Grafton, MA, USA

Part of the welfare considerations practitioners deal with in our patients is the expression of extreme phenotypes or morphology. The “more is better” rule has led to extremes in size (large and small), hair, skin folds, angulation, and the most frequently seen is extreme brachycephaly.

Public preference for dogs and cats with pushed-in noses and bulging eyes has created a breeding environment that has crossed a tipping point in predisposing to disease. Brachycephalic obstructive airway syndrome (BOAS) is a disorder of breathing difficulty in short-snouted and “bully” breeds (especially the popular English Bulldogs, French Bulldogs, and Pugs).1 In Persian and Himalayan cats, BOAS causes chronic sinusitis.2 These dog and cat breeds can also have issues with skin fold dermatitis, corneal ulceration, globe proptosis, dental malocclusion, and dystocia.1

Of the anatomical components of BOAS, stenotic nares, and hypoplastic trachea are inherited. The length of the soft palate and, therefore, soft palate/epiglottis overlap is also inherited. Soft palate thickness (which exacerbates BOAS) is caused by hyperplasia secondary to chronic turbulence, as are everted laryngeal saccules. Laryngeal collapse and hiatal hernia (with regurgitation) are secondary to the effects of negative inspiratory pressure from restricted airflow.

The Incidence of Boas is Rapidly Increasing

BOAS is becoming a greater clinical issue due to the rapidly increasing popularity of the susceptible breeds. Registrations of French Bulldogs have increased 3,000% over the past 10 years.1 As the clinical morbidity of BOAS does not usually manifest until middle age, these rapidly expanding young breed populations will continue to increase their presentation with symptomatic BOAS. Another welfare issue involves the increase of brachycephalic dogs relinquished to shelters and rescue organizations, and the difficulty rehoming dogs with breathing difficulties.

Compounding the matter is the fact that up to 60% of owners do not see their dogs (or cats) as being impaired by BOAS. The “normalization” of brachycephalic stridor also extends to veterinarians: “That’s just how Pugs breath.” However, BOAS dogs are regularly seen - especially in warm weather - with dyspnea, exercise intolerance, heat intolerance, abnormal and increased respiratory noise, sleep disorders, cyanosis, syncope, and death.

Individual dogs in breeds with extreme brachycephaly die younger (median longevity 8.6 years) than dogs in moderate and non-brachycephalic breeds (median 12.7 years). A higher proportion of deaths in extreme brachycephalic breeds are due to upper respiratory disease (16.7%).3

Phenotypic Screening Against BOAS

The genetics of brachycephaly are present in all members of the involved breeds. Therefore, the question becomes, “What is genetically different between dogs in these breeds exhibiting BOAS and those that do not? Part of this question also involves identifying diagnostic criteria that separates BOAS affected and non-affected dogs.

A group at the Royal Veterinary College in Cambridge, UK led by Dr. David Sargan has developed a closed chamber for Whole-Body Barometric Plethysmography (WBBP). A dog’s airflow is measured at rest and after controlled activity. Physiological measurements of airflow volume and pattern consistently separate dogs and breeds with BOAS versus those without BOAS. Based on WBBP, approximately 50% of the study dogs in the three extreme brachycephalic breeds were BOAS affected.1 While WBBP is not practical for widespread screening, its results have allowed studies of other measurements that differentiate between BOAS+ and BOAS- dogs. The data show that roughly 50% of BOAS variation is genetic and 50% is environmental; including exercise, feeding, temperature, and humidity. There are several recorded measurements that are significant in different breeds and sexes. However, stenotic airways and body condition score (obesity) are the most significant factors correlated to the clinical presentation of BOAS across all breeds.4 Stenotic nares are primarily caused by the enlargement of the alar folds that impinge into the nasal opening. Veterinary surgeons demonstrate that surgically correcting stenotic nares relieves most dogs of the clinical signs of BOAS. Surgery removes the lateral alar cartilage. The rule of thumb is to open the nares to a cumulative 1/3 the width of the nose. According to WBBP almost all dogs improve their BOAS index after nares surgery and 40% become BOAS- non- affected.1

Dr. Rowena Packer at the Royal Veterinary College developed a measuring system for stenotic nares. She states that each breed has very specific nares conformation, and breed-specific values would need to be established for setting breeding goals. Studies show 75.4% of French Bulldogs have moderately to severely stenotic nostrils, while prevalence amongst Pugs (65.3%), and English Bulldogs (44.2%) is lower.4

The OFA in the USA (ofa.org) has instituted a pilot database for computer-assisted measurement of nares openings from digital photographs in English Bulldog and other bully breeds. They also have an existing database for evaluating hypoplastic trachea from a lateral radiograph.

The Swedish and Finnish Kennel Clubs have developed standardized working (walking and jogging) tests to document labored breathing as a screening test for BOAS. These walking tests have also been evaluated with WBBP. Studies show English Bulldogs with more severe BOAS walked a shorter distance, more slowly and their recovery from exercise took longer than those with only mild signs of BOAS. Increases in body temperature during exercise were significantly higher in English Bulldogs than in controls.5

Continuing research on the phenotypic screening of BOAS is correlating WBBP, standardized walking tests, and nares and body measurements to more accurately define the BOAS phenotype. Some of these test results could in the future be combined into an estimated breeding value (EBV) to compare between prospective breeding dogs.

Genes Related to BOAS

There are several studies into the genes causing BOAS. Groups of BOAS+ and BOAS- dogs can be compared through DNA analysis. Results show that many genes are involved in BOAS making it a polygenic disorder. Therefore, the task is to identify if there are single genes that have a major effect on BOAS, or if a panel of genes provides a major difference in the liability to develop clinical BOAS. Such a panel would provide a genomic breeding value (GBV) to compare prospective breeding dogs, and possibly differentiate those with a genetic predisposition to become mildly, moderately, or severely affected with BOAS.

Several genetic studies have been conducted to identify genes associated with skull morphology, brachycephaly, and BOAS. Identified genes include IGF1, THSB2, SMOC2, FGF4, and BMP3. However, many of these genes are fixed (non-variable) in brachycephalic and BOAS liable breeds. Therefore, they do not cause a genetic difference between BOAS+ and BOAS- dogs. Studies from the Cambridge group into a regulatory gene affecting SMOC2 expression show that it affects the facial skeleton in a dose-dependent manner and accounts for 36% of facial length differences.6 This group has identified a panel of 11–13 genetic markers that account for 35% of the phenotypic variation in Pugs, 47% in French Bulldogs, and 51% in English Bulldogs. Based on this panel they have been able to predict the most severely affected BOAS dogs in each breed. They also find that those less likely to develop BOAS through GBVs have longer muzzles and wider nares openings.


While several breeds have a high incidence of BOAS, there is still considerable within-breed variation to enable breeders to breed away from genetically susceptible dogs. Current phenotypic screening tests to select against BOAS liability include standardized walking tests (usually administered by breed or kennel clubs), nares and trachea measurements, and selecting for a breed-appropriate but longer muzzle. Based on research models, genetic testing panels against BOAS liability should be available in the near future.

Part of changing the culture that has caused the rapid popularity of extreme brachycephalic breeds is to remove the social media fixation on them. In some studies, more than half of all advertising that includes a dog has a Pug, English Bulldog, or French Bulldog. The British Veterinary Association has called for a moratorium on advertisements containing extreme brachycephalic breeds.

Dog show judge’s education is important to select against the breed extremes of short muzzles and tight nares and to reward moderation of phenotypic morphology. Veterinarians should educate breeders and owners on the morbidity of BOAS. Breeders should use genetic screening in breeding schemes, and prospective owners should seek health-conscious breeders who use genetic screening. Lastly, as environmental aspects influence approximately 50% of the clinical presentation of BOAS, owners can improve their dogs’ health by keeping them slim and fit.


1.  Ladlow J, Liu NC, Kalmar L, Sargan D. Brachycephalic obstructive airway syndrome. Vet Rec. 2018;182(13):375–378. doi: 10.1136/vr.k1403.

2.  Farnworth MJ, Chen R, Packer RM, et al. Flat feline faces: Is brachycephaly associated with respiratory abnormalities in the domestic cat (Felis catus)? PLoS One. 2016;11(8):e0161777. doi: 10.1371/journal.pone.0161777.

3.  O’Neill DG, Jackson C, Guy JH, et al. Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England. Canine Genet Epidemiol. 2015;2:10. doi: 10.1186/s40575–015–0023–8.

4.  Liu NC, Troconis EL, Kalmar L, et al. Conformational risk factors of brachycephalic obstructive airway syndrome (BOAS) in pugs, French bulldogs, and bulldogs. PLoS One. 2017;12(8):e0181928. doi: 10.1371/journal. pone.0181928.

5.  Lilja-Maula L, Lappalainen AK, Hyytiäinen HK, et al. Comparison of submaximal exercise test results and severity of brachycephalic obstructive airway syndrome in English bulldogs. Vet J. 2017;219:22–26. doi: 10.1016/j. tvjl.2016.11.019.

6.  Marchant TW, Johnson EJ, McTeir L, et al. Canine brachycephaly is associated with a retrotransposon-mediated missplicing of SMOC2. Curr Biol. 2017;27(11):1573–1584.e6. doi: 10.1016/j.cub.2017.04.057.


Speaker Information
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Jerold Bell, DVM
Department of Clinical Sciences
Tufts Cummings School of Veterinary Medicine
N. Grafton, MA, USA

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