Canis ISSN: 2398-2942

Juvenile laryngeal paralysis and polyneuropathy

Synonym(s): Laryngeal paralysis-polyneuropathy complex, congenital laryngeal paralysis, JLPP

Contributor(s): Laurent Garosi, Nicolas Granger

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.

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

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Treatment

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Prevention

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Outcomes

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

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) (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 dogsJ 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 RottweilersJ 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 DalmatiansAm 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 (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


ADDED