Genetic Basis of Stargardt Disease

Genetic Basis of Stargardt Disease

Stargardt disease is one of the rare Inherited Retinal Diseases (IRDs) and so it is a disease of genetic origin. It is usually inherited in an autosomal recessive pattern, which means both parents need to be carriers in order to have a 25% chance of having an affected child. The affected person will need to have mutations in both copies of the gene. Carriers of the condition can have one mutated gene and one unaffected copy, and show no characteristics of the disease at all. Stargardt disease can rarely be inherited in an autosomal dominant pattern, where only one mutated gene from one parent is sufficient to cause the condition. You can read more about inheritance patterns here.

There are different forms of Stargardt disease that differ in the gene mutated, in the time of onset and the symptoms that present as part of the condition.

ABCA4 is the gene most commonly mutated in IRDs. In Stargardt disease, bialelic mutations in ABCA4 are a significant cause, with 400 new cases estimated to occur in the USA each year. A mutation in the ELOVL4 gene is responsible for Stargardt disease-3 (STGD3). Stargardt disease-4 is caused by mutation in the PROM1 gene. An incorrect designation of STGD2 to chromosome 13q34 was corrected when the family in question was correctly mapped to chromosome 6q14, which is the same chromosome as STGD3.

Fundus flavimaculatus (FFM) is an allelic subtype of Stargardt disease. FFM has been linked to mutations in the ABCA4 gene and the PRPH2 gene. The timing of onset of vision loss can be a deciding factor in diagnosing FFM  or Stargardt disease. Stargardt disease is diagnosed if visual acuity loss begins in childhood or the teen years. FFM is the preferred diagnosis if the condition begins much later in life and vision loss is more progressive.  

Given the similarities between Stargardt disease and other IRDs, natural history studies and genetic testing are instrumental in understanding the disease progression and the genetic nature of the diseases. You can find out more about genetic testing on our Know Your Code toolkit here.