Gould Syndrome is diagnosed following a genetic test revealing a mutation in the COL4A1 or COL4A2 gene. If either parent carries the mutation, it is considered inherited. If neither parent carries the mutation, it is considered de novo which means that the mutation is a new occurrence. Approximately two-thirds of cases are de novo while one-third are inherited.

In cases where the mutation is inherited, the carrier parent is often mildly affected or unaffected. This can occur if the carrier parent is a mosaic – which means that some cells carry the mutation while other cells do not. The degree of mosaicism is highly variable – ranging from only a small percent of cells with the mutation to nearly all cells carrying the mutation – and depends on the stage during development that the mutation occurred. It is important to discuss these concepts with a genetic counselor and understand their implications.

Signs and symptoms of Gould Syndrome can manifest at almost any age from before birth to old age. The current impression is that Gould Syndrome is more likely to be a childhood or developmental disease. However, this is likely in part to ascertainment bias whereby younger or more severely affected individuals are more likely to have genetic testing performed. As more knowledge is gained, it is likely that older and more mildly affected individuals will continue to be identified. Some individuals do not have any observable symptoms (asymptomatic); others can develop severe, even life-threatening complications. Some may only develop specific symptoms such as isolated migraines or strokes in childhood or adulthood. The variability and severity of symptoms are significant.

While there are currently no cures or treatments available, Dr. Gould’s lab at the University of CA is exploring therapeutic avenues using gene-editing technology, which may potentially help individuals affected with COL4A1/A2 mutations in the future. Working with your team of medical specialists can help optimize your health as you navigate the challenges associated with this rare disease. To help advance understanding and integrate different medical subspecialties, the UCSF Benioff Children’s Hospital has recently launched a Gould Syndrome Center of Excellence.

Our website is filled with resources available to you and your medical team. Clinical consensus and recommendations are ongoing and beginning to emerge. As stated in one of our educational Gould Talks videos, the following is recommended:

1. Continue follow up with your specialists and talk to your doctor about stroke prevention.

2. Conduct regular brain MRIs and angiograms.

3. Monitor ophthalmic findings. Cardiac echogram.

4. Kidney and liver ultrasound or CT.

5. Evaluation of hematuria.

6. Measurement of creatine kinase levels.

7. Establish care with a geneticist.

8. Share test results with family members so they can speak to their healthcare providers about genetic testing. Results could impact their current medical care and/or reproductive risks.

Collagen type IV alpha 1 (COL4A1) and 2 (COL4A2) are extracellular matrix proteins that together constitute a major component of nearly all basement membranes which are specialized sheets of proteins found in every organ. The two genes that code for these proteins are tightly linked on chromosome 13. Dominant COL4A1 and COL4A2 gene variants cause a highly variable, multisystem disorder. It is recommended you work directly with your genetic counselor to help understand your specific gene variant and the effects it may cause.

There are currently over 850 cases reported. Although they are concentrated in countries with health care systems where genetic testing is readily available, affected individuals are expected to be found uniformly all over the world.

You can direct them to the Medical Personnel page on our website here.

The University of California in San Francisco Gould Syndrome Center is a service of the Pediatric Neurology Program. It is the world’s first center dedicated to supporting patients diagnosed with Gould Syndrome. Learn more about the UCSF Gould Syndrome Center here.

Yes. Mutations in COL4A1, and subsequently COL4A2, were first discovered in 2003 by Dr. Douglas Gould. Dr. Gould earned a PhD in Medical Genetics at the University of Alberta in Edmonton, Canada and is now a Professor in the Departments of Ophthalmology and Anatomy at University of California, San Francisco. In 2005-2006, Dr. Gould published manuscripts in Science and The New England Journal of Medicine reporting the discovery of COL4A1 mutations in individuals with porencephaly and small vessel disease. He has dedicated his career to defining and understanding the multi-system disorder caused by COL4A1 and COL4A2 mutations with the help of his team of researchers.

The most common specialists associated with Gould Syndrome are neurology, ophthalmology, physical therapy, occupational therapy, genetics, speech therapy, orthopedics, nephrology, cardiology, and gastroenterology.

Yes! Gould Syndrome Awareness Day is April 12.