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Juvenile laryngeal paralysis and polyneuropathy
Synonym(s): Laryngeal paralysis-polyneuropathy complex, congenital laryngeal paralysis, JLPP
Introduction
- Cause: genetic disease (confirmed or suspected), autosomal recessive trait.
- Signs: exercise intolerance, laryngeal stridor, dysphonia, dyspnea, conscious proprioceptive deficits, distal weakness and collapse.
- Diagnosis: electrophysiology, muscle and nerve biopsy, DNA testing.
- Treatment: none other than supportive and symptomatic surgical correction of laryngeal paralysis (‘tie-back’).
- Prognosis: poor.
Presenting signs
- Loss of exercise tolerance.
- Laryngeal stridor / dysphonia.
- Respiratory distress / dyspnea / collapse.
- For Black Russian terrier dogs: microphthalmia and cataract.
Acute presentation
- Collapse with aspiration pneumonia.
Geographic incidence
- Worldwide.
Age predisposition
- Signs typically start after weaning age and on average between 2 and 12 months.
Breed/Species predisposition
- Breed with genetic mutation confirmed:
- Black Russian Terrier dog Russian Black Terrier.
- Rottweiler Rottweiler.
- Alaskan Huskies - note that the laryngeal paralysis is not the predominant feature in this breed but these dogs did display an abnormal voice.
- Breed with a suspected genetic origin, yet not found:
- Dalmatian Dalmatian.
- Pyrenean Mountain dog Great Pyrennees.
Pathogenesis
Etiology
- Inherited autosomal recessive disease in Black Russian terrier, Rottweiler and Alaskan Husky dogs.
- Previously described as a juvenile onset laryngeal paralysis and polyneuropathy similar to Charcot Marie Tooth disease in humans; original description in Dalmatians (1994) and Rottweilers (1998).
- Recently identified in Black Russian terrier and Alaskan Husky dogs as a model for Warburg micro syndrome (WARBM) which is a severe developmental disorder characterized by abnormalities of the eye, genitals and nervous system including predominantly axonal peripheral neuropathy but also a spongiform encephalopathy.
- Mutation in the Warburg syndrome gene, RAB3GAP1, identified in Black Russian terrier, Rottweiler and Alaskan Husky dogs.
- Heterozygotes have no clinical signs.
Pathophysiology
- Distal denervating process with selective degeneration of the distal long and large diameter axons.
- RAB3GAP1 encodes the catalytic subunit of a GTPase activator protein and guanine exchange factor for Rab3 and Rab18 respectively.
- Rab protein are involved in membrane trafficking in the endoplasmic reticulum, axonal transport, autophagy and synaptic transmission → neuronal vacuolation and membranous inclusion.
Timecourse
- Most affected dogs die or are euthanized at the owners' request due to progressive weakness and/or respiratory distress by 6 months of age.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed Papers
- Recent references from PubMed and VetMedResource.
- Mhlanga-Mutangadura T, Johnson G S, Schnabel R D, Taylor J F, Johnson G C, Katz M L, Shelton G D, Lever T E, Giuliano E, Granger N, Shomper J, O'Brien D P (2016) A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with polyneuropathy and neuronal vacuolation in Black Russian Terrier dogs. Neurobiol Dis 86, 75-85 PubMed.
- Mhlanga-Mutangadura T, Johnson G S, Ashwini A, Shelton G D, Wennogle S A, Johnson G C, Kuroki K, O'Brien D P (2016) A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration. J Vet Intern Med 30 (3), 813-818 PubMed.
- Wiedmer M, Oevermann A, Borer-Germann S E, Gorgas D, Shelton GD, Drögemüller M, Jagannathan V, Henke D, Leeb T (2015) A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1). G3 (Bethesda) 6 (2), 255-262 PubMed.
- Granger N (2011) Canine inherited motor and sensory neuropathies: an updated classification in 22 breeds and comparison to Charcot-Marie-Tooth. Vet J 188, 274-285 PubMed.
- Gabriel A, Poncelet L, Van Ham L, Clercx C, Braund KG, Bhatti S, Detilleux J, Peeters D (2006) Laryngeal paralysis-polyneuropathy complex in young related Pyrenean mountain dogs.
J Small Anim Pract 47 (3),144-1449 PubMed. - Polizopoulou Z S, Koutinas A F, Papadopoulos G C, Saridomichelakis M N (2003) Juvenile laryngeal paralysis in three Siberian husky x Alaskan malamute puppies. Vet Rec 153 (20), 624-627 PubMed.
- Ridyard A E, Corcoran B M, Tasker S, Willis R, Welsh E M, Demetriou J L, Griffiths L G (2000) Spontaneous laryngeal paralysis in four white-coated German shepherd dogs. J Small Anim Pract 41 (12), 558-561 PubMed.
- Mahony O M, Knowles K E, Braund K G, Averill D R Jr, Frimberger A E (1998) Laryngeal paralysis-polyneuropathy complex in young Rottweilers. J Vet Intern Med 12 (5), 330-337 PubMed.
- Braund K G, Shores A, Cochrane S, Forrester D, Kwiecien J M, Steiss J E (1994) Laryngeal paralysis-polyneuropathy complex in young Dalmatians. Am J Vet Res 55 (4), 534-542 PubMed.
- O'Brien J A, Hendriks J (1986) Inherited laryngeal paralysis. Analysis in the husky cross. Vet Q 8 (4), 301-302 PubMed.
- Venker van Haagen A J, Hartman W, Goedegebuure S A (1978) Spontaneous laryngeal paralysis in young Bouviers. JAAHA 14 (6), 714-720 VetMedResource.
Other sources of information
- For information on Genetic Testing Providers (labs), genetic tests, and tests by breed, visit International Partnership for Dogs: https://dogwellnet.com/.
- For a list of DNA tests available for certain breeds worldwide, visit Kennel Club Worldwide DNA tests: https://www.thekennelclub.org.uk/health/for-breeders/dna-testing-simple-inherited-disorders/worldwide-dna-tests/.