Test Detail

Laryngeal paralysis with polyneuropathy type 3 (LPPN3)

Neurological · Dog

Molecular test for laryngeal paralysis associated with polyneuropathy type 3 (LPPN3), an inherited neuropathy that combines laryngeal dysfunction (vocal cord paralysis) with peripheral polyneuropathy with progressive signs. It affects the peripheral nervous system and the larynx, and compromises breathing, exercise and quality of life. The test reports clear/carrier/affected status for the corresponding variant.
Inheritance patternAutosomal recessive
Gene / MutationCNTNAP1 (chromosome 9, CanFam3.1): g.20298261C>T, XM_548083.6:c.2810G>A, p.(Gly937Glu), LPPN3 allele (OMIA002301). Affected homozygotes. Described in Leonberger, Saint Bernard and Labrador Retriever (Letko et al. 2020), and in Great Dane, New Zealand Heading Dog and Pyrenean Shepherd (Shelton et al. 2025; OMIA002301).
PenetranceProbable incomplete penetrance and variable expression in age of onset and severity; published data are limited.
Codeawha
Turnaround time10 days
Price52,60 €

Incidence

Breeds with the described CNTNAP1 c.2810G>A variant: Leonberger, Saint Bernard and Labrador Retriever (Letko et al. 2020), and Great Dane (Shelton et al. 2025), in addition to New Zealand Heading Dog and Pyrenean Shepherd (OMIA002301). Allele frequencies are not systematically published.

Breeder management

- Genotype breeding animals of the affected breeds before mating.
- Autosomal recessive inheritance: do not mate two carriers (25% affected offspring).
- An affected animal must not be bred; a carrier should be mated to a clear animal.
- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer.

Specialist notes

Laryngeal paralysis may be idiopathic, congenital, traumatic or neuropathic: rule out acquired causes before attributing it to LPPN3. Laryngoscopy and electromyography guide the diagnosis. Surgery (arytenoidopexy) improves the airway but does not treat the underlying polyneuropathy. Differentiate from LPN1 (Leonberger, juvenile onset, AR) and from toxic or metabolic polyneuropathies.

References

1. Letko A, Minor KM, Friedenberg SG, et al. A CNTNAP1 Missense Variant Is Associated with Canine Laryngeal Paralysis and Polyneuropathy. Genes (Basel) 2020. PMID:33261176.
2. Shelton GD, Carpentier MC, Kimura YM, et al. A CNTNAP1 Missense Variant Associated With Laryngeal Paralysis and Polyneuropathy in Young Great Dane Dogs. J Vet Intern Med 2025. PMID:40622077.
3. Ekenstedt KJ, Becker D, Minor KM, Shelton GD, et al. An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs. PLoS Genet 2014. PMID:25275565.
4. Becker D, Minor KM, Letko A, et al. A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs. BMC Genomics 2017. PMID:28841859.

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