Neonatal Cerebellar Cortical Degeneration

Neonatal cerebellar cortical degeneration (CCD) or neonatal cerebellar abiotrophy is a neurodegenerative disease first described in Beagle dogs. The pathology renders affected dogs unable to move normally from the time they begin to walk.

Symptoms

In Beagle dogs, the first symptoms are observed when the dogs begin to walk at about three weeks of age. Affected puppies present with loss of balance, altered gait with inability to regulate rhythm and range of motion, and tremors. Progression of clinical signs is minimal. Degeneration and loss of Purkinje cells of the cerebellum occurs.

Disease Management

There is currently no cure for neonatal CDD in dogs. Treatment focuses on controlling symptoms and providing supportive care to help maintain the affected dog's quality of life. This may include physical therapy, assistive devices and medication to control tremors and other symptoms. The prognosis for dogs is variable and in severe cases, euthanasia may be considered.

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

The spinocerebellar ataxias are a genetically heterogeneous group of disorders characterized by postural abnormalities, motor deficits and cerebellar degeneration including neonatal cerebellar cortical degeneration. Spectrin β-III, a cytoskeletal protein present in the soma and dendritic tree of cerebellar Purkinje cells, is required for the maintenance of dendritic architecture. Spectrin β-III is encoded by the SPTBN2 gene that has been shown to be potentially altered in CDD. Forman et al. discovered an 8 base pair deletion in the SPTBN2 gene sequence, which could be the cause of neonatal CDD in Beagle dogs. This deletion affects exon 29 of SPTBN2 and generates a premature stop codon, resulting in the production of a truncated protein.

Most affected breeds

Beagle

Bibliography

Forman OP, De Risio L, Stewart J,et al. Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genet. 2012 Jul 10;13:55.