Cerebellar Ataxia Finnish Hound Type (FHA/CAFH)
Cerebellar Ataxia Finnish Hound Type (FHA/CAFH) is an inherited neurological disorder affecting the Finnish Hound dog breed. There are different forms of ataxias recognized. First time form of hereditary ataxia was reported in Smooth-Haired Fox Terrier in 1957, which was followed by report of a disease with similar symptoms in the Jack Russell Terrier in the 1973. Another form of ataxias are cerebellar ataxia and spinocerebellar ataxia. Different forms of ataxia differ from each other in ages of onset, clinical signs, and histopathologic changes. Hereditary ataxias have been identified in many species, also in humans and dogs.
Characteristics and Symptoms
Cerebellar Ataxia Finnish Hound Type (FHA/CAFH) is an early onset and a rapidly progressive form of ataxia and affected dogs start to show clinical signs by the age of 3 months. The cerebellum is a region of brain important for movement control. Cerebellar ataxia is characterized by degeneration of the cerebellar structure, in form of cerebellar shrinkage detectable through MRI. The cerebellar degeneration results in motor incoordination and affected puppies do not manage to coordinate their movements and balance. Brain examination shows loss of cortical Purkinje cells, as primary target of degenerative process. Loss of Purkinje cells is followed by secondary changes in other cortical cell layers. Areas of damaged tissue in the brain are called brain lesions. These lesions are the cause of dog’s lack of balance, eye movements and extremities. Any or both sides of brain can be affected by lesions and movement difficulties are connected to which side of brain the lesions are. Due to rapid affected puppies are euthanized soon after diagnosis of the disorder.
Cerebellar Ataxia Finnish Hound Type (FHA/CAFH) is caused by a mutation of the SEL1L gene. SEL1L protein is a part of a protein complex in the endoplasmatic reticulum, a structure in cells that ensures mutation free proteins, which need to be packaged correctly and sent to specific location in the body. In case of mutation of SEL1L, protein packaging process fails, causing the endoplasmatic reticulum stress and cell death or apoptosis.
The disorder is inherited as an autosomal recessive trait. The dog can be clear, carrier or affected. For dog to be affected, it needs to have two copies of the mutated gene. Healthy parents of an affected dog are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Kyöstilä K, Cizinauskas S, Seppälä EH, Suhonen E, Jeserevics J, Sukura A, Syrjä P, Lohi H. 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.