Characterization and Mode of Inheritance of a Paroxysmal Dyskinesia in Chinook Dogs

Abstract

Background: Paroxysmal dyskinesias are episodes of abnormal, involuntary movement or muscle tone, distinguished from seizures by the character of the episode and lack of seizure activity on ictal EEG.Hypothesis: Paroxysmal dyskinesia is an inherited, autosomal recessive disorder in Chinook dogs. Animals: Families of Chinook dogs with paroxysmal dyskinesia. Methods: Pedigrees and medical histories were reviewed for 299 Chinook dogs. A family of 51 dogs was used for analysis. Episodes were classified as seizures, paroxysmal dyskinesia, or unknown, and segregation analysis was performed.Results: Paroxysmal dyskinesia was identified in 16 of 51 dogs and characterized by an inability to stand or ambulate, head tremors, and involuntary flexion of 1 or multiple limbs, without autonomic signs or loss of consciousness. Episode duration varied from minutes to an hour. Inter-ictal EEGs recorded on 2 dogs with dyskinesia were normal. Three dogs with dyskinesia also had generalized tonic-clonic seizures. One of 51 dogs had episodes of undetermined type. Phenotype was unknown for 6 of 51 dogs, and 28 dogs were unaffected. Segregation was consistent with an autosomal recessive trait.Conclusions and Clinical Importance: This movement disorder is prevalent in the Chinook breed, and consistent with a partially penetrant autosomal recessive or polygenic trait. Insufficient evidence exists for definitive localization; episodes may be of basal nuclear origin, but atypical seizures and muscle membrane disorders remain possible etiologies. The generalized seizures may be a variant phenotype of the same mutation that results in dyskinesia, or the 2 syndromes may be independent.

Paroxysmal Dyskinesia in Norwich Terrier Dogs

“…PxDs have been described in other canine breeds . In the majority of breeds with PxD affecting the limbs and trunk, the first episode of PxD is observed in the first year after birth .…”

Canine Paroxysmal Movement Disorders

“…Dogs are neurologically normal between episodes and interictal analysis including pre and post exercise lactate and pyruvate levels, EEG, magnetic resonance imaging, and cerebrospinal fluid examination from 2 affected dogs, was unremarkable. 9 An autosomal-recessive mode of inheritance has been identified by segregation analysis and it is interesting to note that epilepsy also occurs in the same family lines, and even coincidentally with PNKD in 2 dogs. The causative genetic disorder has not yet been determined.…”

“…9 Initially, these episodes were known as Chinook seizures, but closer examination revealed that the episodes were not epileptic. Episodes are not triggered by sudden movements or exercise, and can last between 1 and 60 minutes.…”

A homozygous PIGN missense mutation in Soft-Coated Wheaten Terriers with a canine paroxysmal dyskinesia

“…Published reports have provided clinical descriptions of primary canine PxD (cPxD) or cPxD-like diseases in several breeds including the Bichon Frise [24], Border Terrier [25], Cavalier King Charles Spaniel [26], Chinook [27], Doberman Pinscher [28], English Bulldog [29], Scottish Terrier [30], and Soft-Coated Wheaten Terrier (SCWT) [31]. Unlike the human primary PxD that are almost always dominant traits, the cPxD usually have a recessive mode of inheritance.…”