Laryngeal paralysis in Miniature Bull Terriers and Bull Terriers

Laryngeal Paralysis (LP) is the inability to abduct the arytenoid cartilages during inspiration due to defective function of laryngeal nerves. This results in a partial to complete obstruction of airways and consequent respiratory distress. The clinical signs may vary and may include respiratory murmur, wheezing, cyanosis, voice impairment, extreme breathlessness when exercising, life-threatening episodes of breathing difficulties and suffocation. In some cases, the respiratory difficulties can be fatal.

There are many different forms of LP with different aetiology. Predispositions of various breeds to this disease are influenced by various genetic factors. In Miniature Bull Terriers, a genetic mutation has been identified that presents a major risk factor for early onset of LP.

It is a 36 bp insertion into a coding exon 15 of the RAPGEF6 gene (c.1793_1794ins36). This mutation leads to the shifting of the reading frame and premature stop codon and results in a loss-of-function allele.

The mode of inheritance of this disease is multifactorial. It means that other genetic factors and/or environmental factors contribute to development of LP. However, the main genetic factor is the recessive allele for the above-mentioned mutation. Dogs that are homozygous for the insertion in the RAPGEF6 gene (they inherit one copy of the defective gene from each parent) have a 10 – to 17-fold increased risk to develop LP.  Heterozygotes inherit the defective gene only from one parent and are clinically normal carriers of the trait but can pass on the risk factor for LP to their offspring.  If two heterozygous dogs are mated, there will be theoretically 25 % of the offspring completely healthy, 50 % will be healthy carriers of the trait and 25 % of the offspring inherit the mutated allele from both parents and the risk for development of laryngeal paralysis will be essentially increased.

.

Reference:

Hadji Rasouliha, S., Barrientos, L., Anderegg, L., Klesty, C., Lorenz, J., Chevallier, L., Jagannathan, V., Rösch, S., Leeb, T. : A RAPGEF6 variant constitutes a major risk factor for laryngeal paralysis in dogs. PLoS Genet 15:e1008416, 2019.