Genetic basis of Airway Distress Syndrome in dogs - also known as Upper Airway Syndrome (UAS) or linked to Brachycephalic Obstructive Airway Syndrome (BOAS) in brachycephalic breeds, is associated with a mutation in the ADAMTS3 gene. The ADAMTS3 gene encodes a metalloproteinase involved in extracellular matrix regulation and lymphatic development. The identified mutation is a missense variant (c.2786G>A) found notably in Norwich Terriers, French Bulldogs, English Bulldogs, and Pugs. This mutation is inherited in an autosomal recessive manner, where dogs homozygous for the mutation (two copies) are at significantly higher risk of developing airway disease symptoms. Heterozygous dogs (one copy of the mutation) may carry the risk allele but generally show milder or no symptoms.
Pathophysiology - The mutation in ADAMTS3 disrupts its normal function, leading to airway oedema (swelling caused by fluid retention in tissues lining the airways). This swelling narrows the airways and contributes to respiratory obstruction and breathing difficulties. The syndrome affects breeds beyond those with brachycephalic skull shapes, showing that face shape is not the only factor. Fluid retention and tissue swelling are key pathological features that exacerbate airway obstruction.
Complications - Affected dogs show signs of: Labored or noisy breathing. Exercise intolerance. Heat intolerance. Cyanosis (blueness due to low oxygen). Collapse in severe cases. Airway swelling worsens obstruction and can complicate surgical treatments often used for brachycephalic obstructive airway syndrome.
Why This Matter to Breeders and Vets - Understanding the genetic risk from the ADAMTS3 mutation helps distinguish genetic predisposition from purely anatomical causes (like skull shape). Genetic testing for this mutation is vital in at-risk breeds to identify carriers and affected dogs. Responsible breeding strategies can reduce the incidence of airway diseases related to this mutation, improving respiratory health and welfare. Veterinarians can better manage, diagnose, and prognosticate airway diseases by knowing the dog's genetic status.
Summary - Airway Distress Syndrome linked to the ADAMTS3 gene mutation is an autosomal recessive genetic risk factor for airway oedema and breathing difficulties in dog breeds such as Norwich Terriers, French and English Bulldogs, and Pugs. The mutation contributes to fluid retention and airway swelling that exacerbate respiratory obstruction. Genetic testing and informed breeding strategies are pivotal in managing disease risk, enhancing respiratory health, and improving outcomes for breeds susceptible to this condition.