Spinocerebellar ataxia in the Bouvier des Ardennes breed is caused by a KCNJ10 missense variant

J Vet Intern Med. 2022 Nov 25. doi: 10.1111/jvim.16594. Online ahead of print.

Abstract

Background: In Belgian Malinois, a KCNJ10 variant causes progressive spinocerebellar degeneration.

Hypothesis/objectives: Describe the clinical, diagnostic, pathological and genetic features of spinocerebellar degeneration in the Bouvier des Ardennes breed.

Animals: Five affected Bouvier des Ardennes puppies with spinocerebellar ataxia (SCA), 8 healthy related dogs, and 63 healthy unrelated Bouvier des Ardennes.

Methods: Sequential case study.

Results: Clinical signs started at 6 weeks of age in 1 puppy with severe signs of cerebellar disease, and at 7 to 10 weeks of age in the 4 remaining puppies with milder signs of spinocerebellar disease. The first puppy displayed severe intention tremors and rapidly progressive generalized hypermetric ataxia, whereas the 4 others developed a milder progressive SCA. Euthanasia after progression to nonambulatory status was performed by 8 weeks of age in the first puppy, and before 11 months of age in the 4 remaining puppies. Histopathology revealed cerebellar spongy degeneration and a focal symmetrical demyelinating myelopathy. All cases were homozygous for KCNJ10 XM_545752.6:c.986T>C(p.(Leu329Pro)), which is pathogenic for SCA with (or without) myokymia, seizures or both (SAMS) and spongy degeneration and cerebellar ataxia (SDCA) 1 in Belgian Malinois dogs. All sampled parents were heterozygous and none of the healthy dogs were homozygous for this recessive variant. This variant has an allele frequency of 15% in the 63 healthy dogs studied.

Conclusions and clinical importance: Inherited spinocerebellar degeneration also affects the Bouvier des Ardennes breed and is caused by a KCNJ10 variant. It can present with a spectrum of severity grades, ranging from severe cerebellar to milder spinocerebellar signs.

Keywords: SAMS; SDCA; demyelinating myelopathy; hypermetric ataxia; intention tremors; spongy degeneration.