Retinal atrophy, generalized (Stargardt Disease)

Gene: ABCA4

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Insertion, ABCA4 gene; c.4176 ins.C, p.(F1393L fs STOP 3), exon28

Medical system: Ocular

Breeds: American Staffordshire Terrier/Amstaff, Chihuahua, German Shepherd, German Shorthaired Pointer, Golden Retriever, Great Dane, Great Pyrenees, Labrador Retriever, Pembroke Welsh Corgi, Poodle - Standard, Rottweiler, Schnauzer - Giant, Siberian Husky

Age of onset of symptoms: Variable; symptoms may appear at an early age or during adulthood.

Stargardt’s disease is a form of genetic retinal degeneration identified in Labrador Retrievers. Both types of retinal photoreceptors are affected: the cones, which enable colour vision and vision in bright light, and the rods, which enable vision in dim light.  During the course of the disease there is a progressive bilateral deterioration of the retina with a reduction in the number of photoreceptors and a slight to moderate reduction in retinal blood vessels. Examination by an ophthalmologist will reveal retinal atrophy with macular lesions, accumulation of lipofuscin deposits (metabolic waste products) and isolated alteration of the foveolar reflection.  It should be noted that affected dogs do not go completely blind but retain partial vision and thus a degree of autonomy and a normal life expectancy.

Although Stargardt’s disease has been described in the Labrador Retriever, a recent review of pathological mutations (Donner et al. 2023) revealed that the mutation responsible for Stargardt’s disease is found in a number of other breeds of dog.  A DNA test is now available which will allow breeders to begin to eliminate this mutation.

References:

OMIA link: [2179-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Ekesten B, Mäkeläinen S, Ellis S, et al. (2022) Abnormal appearance of the area centralis in Labrador Retrievers with an ABCA4 loss-of-function mutation. Transl Vis Sci Technol 11:36. [pubmed/35201338]
Genetics Committee of the American College of Veterinary Ophthalmologists. (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]
Mäkeläinen, S., Gòdia, M., Hellsand, M, et al. (2019) An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLoS Genet 15:e1007873. [pubmed/30889179]

Contributed by:  Dominique Marullo-Masson and Emmanuelle Marullo Masson, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).