Progressive Early-Onset Cerebellar Ataxia

Ataxia is an inherited disorder characterized by degeneration of cerebellar structures, resulting in a progressive lack of coordination in movements.

Symptoms

Early onset progressive cerebellar ataxia is characterized by the manifestation of nonspecific clinical signs that usually present around 3 months of age in affected dogs. As the disease progresses rapidly, there is a marked lack of coordination and balance in movement, making it difficult to perform fine motor tasks, walk normally and maintain proper posture. Other common symptoms include the presence of involuntary tremors and growth retardation.

Disease Management

Currently, there is no cure for early onset progressive cerebellar ataxia. Management of the disease focuses on creating a safe environment for the dog and providing mobility assistance through physical therapy and specific exercises to improve coordination and balance.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Early onset progressive cerebellar ataxia is a rapidly progressive disorder with a poor prognosis that has been associated with a nonsense mutation (c.1972T>C) in the SEL1L gene. This mutation affects a highly conserved residue in an evolutionarily conserved protein motif. The SEL1L gene is responsible for encoding a protein that is part of a protein complex responsible for endoplasmic reticulum-associated degradation (ERAD), a crucial cellular process for the removal of misfolded or disassembled polypeptides. The described mutation affects the functionality of this protein and it has been shown that endoplasmic reticulum stress and altered protein degradation are contributing factors in several neurodegenerative diseases, including early onset progressive cerebellar ataxia.

Most affected breeds

Finnish Hound

Bibliography

Kyöstilä K, Cizinauskas S, Seppälä EH,et al. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD) machinery. PLoS Genet. 2012;8(6):e1002759.