Test Detail

Paroxysmal movement disorder of the Shetland Sheepdog (Sheltie) triggered by exercise and stress. The episodes combine generalised ataxia with hypermetria, muscle hypertonia of the four limbs, dystonia and mild tremor, with normal or mildly altered mental state, and last from minutes to several hours. It has been associated with a heterozygous variant in PCK2, which encodes mitochondrial phosphoenolpyruvate carboxykinase.

Affected breed: Shetland Sheepdog. Published cases are infrequent and concentrated in related females; the true population frequency is not reliably known.

- Identify carriers of the PCK2:c.1658G>A variant before breeding\n- Avoid mating carrier animals with each other because of the suspected dominant inheritance\n- Consider environmental management (stress control, avoiding intense exercise and heat) in affected animals\n- Consider a gluten-free diet rich in tryptophan or seafood and treatment with acetazolamide or zonisamide, which have been associated with partial reduction of episodes\n- Do not replace genetic prevention with clinical management

Differential diagnosis with other canine paroxysmal dyskinesias (episodic falling in the CKCS due to BCAN, PxD in the SCWT due to PIGN) and with motor epilepsy. The video of the episode and the exercise-stress association are indicative. The PCK2 variant is considered a candidate and not a definitive diagnosis: it should be interpreted together with the clinical picture. The response to a gluten-free diet in some cases suggests additional mechanisms to be investigated.

1. Nessler J et al. 2020. Mitochondrial PCK2 missense variant in Shetland Sheepdogs with paroxysmal exercise-induced dyskinesia (PED). Genes (Basel) 11:774. PMID: 32660061
2. OMIA:002868-9615 - Dyskinesia, paroxysmal, PCK2-related. https://omia.org/OMIA002868/9615/