About GRIN Disorders
What are GRIN disorders?
GRIN Disorders are rare genetic conditions with severe life-limiting consequences. Many GRIN patients are non-verbal, unable to walk, and many cannot feed or toilet themselves. They often suffer severe and frequent seizures that are not responsive to medical therapies.
GRIN Disorders are caused by a change in one of seven GRIN genes including GRIN1, GRIN2A, GRIN2B, and GRIN2D.These genes contain the code to create NMDA receptors, which are essential for learning and memory. Most cases are de novo (not inherited from the parent) missense mutations where a single letter is “misspelled” among the 3.2-billion letters of human DNA.
Diagnosing GRIN1, GRIN2A, GRIN2B, and GRIN2D
Parents of children with GRIN Disorders typically notice that something is wrong when infants begin missing milestones. GRIN Disorders are usually diagnosed by genetic testing called Genome sequencing. As genetic tests become more affordable, it is increasingly common for children to be diagnosed before the age of two. However, without a genetic diagnosis, some individuals are incorrectly diagnosed with cerebral palsy, autism or another genetic disorder such as Angelman Syndrome.
cortical visual impairment (CVI)
hypotonia (low tone)
constipation (GI Issues)
limited or non-verbal communication
Most common symptoms of GRIN Disorders
The standard GRIN genes are made up of hundreds of letters of genetic code. Sometimes the letters can appear in the wrong order, get swapped for different ones, or be missed out altogether. Any of these occurrences can cause the gene to not work properly. We have found that the most common errors in GRIN patients are ‘missense’ variants, where one letter of DNA gets swapped for a different one.
Scientists are still working to understand the impact these variations can have. The most important difference seems to be that some variants result in the NMDA receptor receiving too much information (known as ‘Gain of Function’ or GoF variants) while others result in it receiving too little (known as ‘Loss of Function’ or LoF variants). Understanding which type of variant is affecting a patient makes it possible to identify appropriate treatment options, including different types of drugs that may help.
Why (or how) does this happen?
Most GRIN patients have a ‘de novo’ gene variant, meaning that this change in their genes happened by chance, around the time of conception. Their condition has not been inherited from either parent; there is nothing that parents could have done differently, and the chances of having another child in the same family with the same mutation are extremely rare.
A small minority of GRIN patients are thought to have inherited their variant from their parents. It is possible that where the disorder has been inherited, other siblings may also carry the variant without being affected but could in theory pass this on to their own children.
What do I do now?
The CureGRIN Foundation provides support to individuals with GRIN Disorders and their families through education and information. Another great way to learn about GRIN Disorders is to connect with and learn from other parents in one of the following Facebook communities.
© 2020 by CureGRIN Foundation