Genetic basis - Generalised Myoclonic Epilepsy (JME) in Rhodesian Ridgebacks is inherited in an autosomal recessive manner. It is caused by a 4-base pair deletion mutation in exon 2 of the DIRAS1 gene, leading to a frameshift and loss of a stop codon. This mutation is specific to Rhodesian Ridgebacks and results in dysfunction of the DIRAS1 protein, which is expressed in the brain and heart and likely plays a role in acetylcholine neurotransmission at neuromuscular junctions and neuronal development
Pathophysiology - The DIRAS1 protein normally influences cholinergic neurotransmission, brain excitability, cognitive functions, and neuronal network development. The mutation impairs these functions, which disrupts excitatory and inhibitory neural signaling. This leads to myoclonic epilepsy characterized by frequent muscle twitches, seizures, and photosensitivity (reaction to flashing lights). The disease typically begins in young dogs, between 6 weeks and 18 months of age.
Complications - Frequent myoclonic muscle jerks, especially when resting or sleeping. Generalized tonic-clonic (grand mal) seizures in some cases. Photosensitivity to flashing or bright lights in affected dogs. Seizures vary in frequency and severity and can lead to chronic neurological impairment if untreated. Potential side effects of anti-epileptic drugs include lethargy, anxiety, loss of coordination, making management complex
Why This Matters to Breeders and Vets - this is a serious inherited neurological disorder that impacts Rhodesian Ridgebacks’ health and quality of life. Breeders benefit from genetic testing to reduce disease prevalence in the population. Veterinarians gain from awareness for timely diagnosis, treatment, and client education on prognosis and genetic counselling. Coordinated efforts between vets and breeders support better disease management and improved breed welfare.