Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs

Polidoro, Dakir; Ham, Luc Van; Santens, Patrick; Cornelis, Ine; Charalambous, Marios; Broeckx, Bart J. G.; Bhatti, Sofie

doi:10.1111/jvim.15804

Cited by 14 publications

(19 citation statements)

References 33 publications

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“…12 Nevertheless, even if not showing overt pain, dogs affected by PMDs could show signs of discomfort. 13 The objective demonstration of MCs in veterinary medicine remains difficult. Despite they present specific features on electromyography, this diagnostic test in dogs requires anesthesia and it is almost impossible to be performed during the attacks.…”

Section: Treatment and Outcomementioning

confidence: 99%

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Clinical features of muscle cramp in 14 dogs

Gagliardo

Ruggeri

Paola

et al. 2020

Veterinary Internal Medicne

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Background Muscle cramps (MCs) are prolonged, involuntary, painful muscle contractions characterized by an acute onset and short duration, caused by peripheral nerve hyperactivity. Objectives To provide a detailed description of the clinical features and diagnostic findings in dogs affected by MCs. Animals Fourteen dogs. Methods Multicenter retrospective case series. Cases were recruited by a call to veterinary neurologists working in referral practices. Medical records and videotapes were searched for dogs showing MCs. The follow‐up was obtained by telephone communication with the owner and the referring veterinarian. Results Three patterns of presentation were identified depending on the number of affected limbs and presence/absence of migration of MCs to other limbs. In 9/14 (64%) of dogs, MCs were triggered by prompting the dogs to move. 8/14 (58%) dogs were overtly painful with 6/14 (42%) showing mild discomfort. The cause of MCs was hypocalcemia in 11/14 (79%) dogs: 9 dogs were affected by primary hypoparathyrodism, 1 dog by intestinal lymphoma and 1 dog by protein losing enteropathy. In 3/14 cases (21%) the cause was not identified, and all 3 dogs were German Shepherds. Conclusions and Clinical Importance Muscle cramps can manifest in 1 of 3 clinical patterns. Muscle cramps are elicited when dogs are encouraged to move and do not always appear as painful events, showing in some cases only discomfort. The main cause of MCs in this study was hypocalcemia consequent to primary hypoparathyroidism. In dogs having MCs of unknown etiology, idiopathic disease or paroxysmal dyskinesia could not be ruled out.

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Section: Treatment and Outcomementioning

confidence: 99%

“…Unlike MCs, PMDs are considered painless 12. Nevertheless, even if not showing overt pain, dogs affected by PMDs could show signs of discomfort 13. The objective demonstration of MCs in veterinary medicine remains difficult.…”

mentioning

confidence: 99%

Clinical features of muscle cramp in 14 dogs

Gagliardo

Ruggeri

Paola

et al. 2020

Veterinary Internal Medicne

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“…Between the episodes, motor functions are normal and there are no neurological deficits, despite the visible dramatic clinical signs during an attack. Paroxysmal dyskinesias have been described in several dog breeds with variable clinical presentations and outcomes (Packer et al 2010;Black et al 2014;Gill et al 2012;Lowrie et al 2016;Kolicheski et al 2017;Polidoro et al 2020). Breed predisposition points to an inherited origin and causative mutations have been found in BCAN in the Cavalier King Charles Spaniel with episodic falling (OMIA 001592-9615) and in PIGN in Soft Coated Wheaten Terriers with PD (OMIA 002084-9615; Gill et al 2012;Kolicheski et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Breed predisposition points to an inherited origin and causative mutations have been found in BCAN in the Cavalier King Charles Spaniel with episodic falling (OMIA 001592-9615) and in PIGN in Soft Coated Wheaten Terriers with PD (OMIA 002084-9615; Gill et al 2012;Kolicheski et al 2016). In Malteser dogs and Border terriers, PD is most likely induced by gluten and hence called paroxysmal gluten-sensitive dyskinesia (Stassen et al 2017;Lowrie et al 2018;Polidoro et al 2020). The Markiesje is a small Dutch breed of middle-sized dogs that is only recognized by the Dutch Kennel Club.…”

Section: Introductionmentioning

confidence: 99%

A knockout mutation associated with juvenile paroxysmal dyskinesia in Markiesje dogs indicates SOD1 pleiotropy

et al. 2021

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A juvenile form of paroxysmal dyskinesia segregated in the Markiesje dog breed. Affected pups exhibited clinical signs of a severe tetraparesis, dystonia, cramping and falling over when trying to walk. In most cases, the presentation deteriorated within weeks and elective euthanasia was performed. Pedigree analysis indicated autosomal recessive inheritance. Genome-wide association and homozygosity mapping of 5 affected dogs from 3 litters identified the associated locus on chromosome 31 in the region of SOD1. The DNA sequence analysis of SOD1 showed that the patients were homozygous for a frameshift mutation in the fourth codon. None of the other analyzed dogs of the breed was homozygous for the mutation, indicating full penetrance of the genetic defect. Mutations in SOD1 are known to cause recessive degenerative myelopathy in middle-aged dogs with low penetrance and dominant amyotrophic lateral sclerosis in humans with variable age of onset. Our findings are similar to recent observations in human patients that a loss of function mutation in SOD1 leads to a juvenile neurologic disease distinct from amyotrophic lateral sclerosis.

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“…The molecular cause has not yet been reported in the scientific literature [8][9][10]. Related phenotypes also with unclear causative genetic defects were reported in Bichon Frisé [11,12], Border Terriers [13][14][15], Boxers [16], Chinooks [17], German Shorthair Pointers [18], Jack Russell Terriers [19] and Maltese dogs [20].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)

Neßler

Hug

Mandigers

et al. 2020

Genes

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Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant.

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Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs

Cited by 14 publications

References 33 publications

Clinical features of muscle cramp in 14 dogs

Clinical features of muscle cramp in 14 dogs

A knockout mutation associated with juvenile paroxysmal dyskinesia in Markiesje dogs indicates SOD1 pleiotropy

Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)

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