Categories: Behaviour / neurological phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607862 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

Molecular basis: Wielaender et al. (2017): "a 4-bp deletion in the exon 2 of the DIRAS1 gene (c.564_567delAGAC . . . CanFam3 . . . , resulting in a frameshift and a stop loss. . . . The genotyping of the DIRAS1 deletion in 14 clinically verified RR cases and 26 controls revealed a homozygous mutant genotype in all cases, a heterozygous genotype in the obligate carriers, and the homozygous wild-type genotype in controls."

Clinical features: Affected Rhodesian Ridgeback (RR) dogs present with frequent myoclonic twitches that tend to begin between the age of 6 weeks and 18 months old. These episodes can be triggered by visual stimuli including flashing lights, sudden light exposure or flickering light (Wielaender et al., 2017). Generally, episodes begin when animals are recumbent and relaxed, but occasionally occur when dogs are standing (Wielaender et al., 2017). Twitches are mainly seen in the musculature of the trunk and proximal limb, as well as in cervical musculature and masticatory muscles (Wielaender et al., 2017). In 38% of dogs, the disease advanced to generalised tonic-clonic seizures within 6 months (Wielaender et al., 2017). No changes in behaviour have been noted prior to seizure episodes (Wielaender et al., 2017). Wielaender et al., 2018: "Absence seizures represent another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs." IT thanks DVM student Emily Gee, who provided the basis of this contribution in May 2023.

Breed: Rhodesian Ridgeback (Dog) (VBO_0201135).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: