Test Detail

Early-onset laryngeal paralysis in the Bull terrier and Miniature Bull terrier in which an insertion in the RAPGEF6 gene acts as a major risk factor. It is a multifactorial trait: the variant modulates risk but does not determine it, so homozygosity should be interpreted as increased risk and not as a diagnosis of disease.

The allele was found in Bull terrier and Miniature Bull terrier and was absent in more than 1000 controls of other breeds (Hadji Rasouliha et al. 2019); no published population prevalence.

- Change or hoarseness of the voice
- Laryngeal stridor and respiratory noise
- Exercise intolerance
- Dyspnoea and cyanosis in severe cases
- Early onset in the breed

Hadji Rasouliha et al. (2019) localized by GWAS a major risk factor for early-onset laryngeal paralysis in Miniature Bull terriers and described a 36-bp insertion in RAPGEF6 (c.1793_1794ins36), with recessive risk-allele inheritance.

- Do not interpret homozygosity as a diagnosis: it is a risk factor, not deterministic
- It can be used as a selection tool in affected lines
- Combine with clinical assessment of the airway and family history
- Avoid presenting it as a diagnostic test or sole exclusion criterion
- Inform about its multifactorial nature

Differential diagnosis with other hereditary laryngeal paralyses/polyneuropathies (RAB3GAP1, CNTNAP1, ARHGEF10, GJA9, SBF2). Because of its multifactorial nature, integrate the result with the clinical phenotype.

Hadji Rasouliha S et al. 2019. A RAPGEF6 variant constitutes a major risk factor for laryngeal paralysis in dogs. PLoS Genet. PMID: 31647804