Part of the official UK Kennel Club testing scheme in English Setter and Gordon Setter
Neuronal ceroid lipofuscinosis (NCL) is a progressive neurodegenerative disease characterised by brain and retinal atrophy. The lipopigment lipofuscin builds up in the neural cells and some organs, such as liver, spleen, kidneys etc. This storage causes neuronal loss, cortical atrophy, and cerebellar and retinal degeneration resulting in seizures, progressive deterioration of cognition (dementia), motor function impairment (involuntary movements, myoclonus, ataxia, spasticity) and blindness.
Affected dogs appear normal at birth but begin to exhibit clinical effects early in life – around 14-18 months of age, when reduced vision and mental dullness become apparent. Progressive loss of vision, lack of muscle coordination and an abnormally stiff gait are noticed shortly thereafter. Within a few months of disease onset, seizures begin and are often the cause of death in an affected dog. Death or euthanasia usually occurs by 2 years of age.
The missense variant in the gene called CLN8 that causes Neuronal Ceroid Lipofuscinosis in English Setter and Gordon Setter is autosomal recessive. This means that dogs that carry two copies of the mutation (homozygotes) will almost certainly develop Neuronal Ceroid Lipofuscinosis during their lives. Dogs that carry a single copy of the mutation (also known as carriers or heterozygotes) will not develop Neuronal Ceroid Lipofuscinosis as a result of the CLN8 mutation, but they will pass the mutation onto about half of any offspring they have. Breeding dogs that will not develop Neuronal Ceroid Lipofuscinosis should be the breeder’s priority, with a reduction in mutation frequency within the whole breed being the secondary, longer-term target.
Carriers can be bred from safely, provided they are mated to a dog that has also been tested and is clear of the CLN8 mutation (i.e. carry no copies of the mutation). If a carrier is mated to a clear dog approximately half of the resulting puppies will also be carriers, so should be tested themselves prior to breeding. Breeding carriers to tested, clear dogs is safe, in terms of avoiding dogs affected with Neuronal Ceroid Lipofuscinosis, and will help to maintain the genetic diversity of a breed. It is therefore encouraged, particularly in the first few generations following the availability of a new genetic test, so that other desirable characteristics and traits can be preserved before the frequency of the disease mutation within the breed is gradually reduced.