CRPS is not directly inherited through a single gene, but genetics do play a role in who develops it. Research has identified specific immune-system genes that appear more often in people with CRPS, and documented families where multiple relatives are affected. The condition is best understood as having a genetic susceptibility component, meaning certain people may be biologically more vulnerable to developing CRPS after an injury, rather than inheriting the condition itself.
What the Family Studies Show
The strongest evidence that genetics matter comes from research documenting CRPS running in families. A study identifying familial cases found 31 families with two or more affected relatives. Among those families, two had five affected members, four families had four affected members, and eight families had three. That’s a striking pattern for a condition that affects a relatively small percentage of the general population.
This doesn’t prove CRPS is hereditary in the way something like sickle cell disease is hereditary, where a single gene mutation gets passed down and directly causes the condition. Instead, it suggests that shared genetic traits within families can make certain people more prone to developing CRPS when the right trigger occurs, usually an injury, surgery, or fracture.
Immune System Genes Linked to CRPS
The most consistent genetic finding involves a part of your immune system called HLA, a group of proteins that help your body distinguish its own cells from foreign invaders. People with CRPS are more likely to carry a specific variant called HLA-DQ8 (technically HLA-DQB1*03:02). In one study, carrying this variant increased the odds of having CRPS by about 65% compared to people without it.
Interestingly, a second variant called HLA-B62 was linked only to CRPS patients who also had dystonia, a movement disorder involving involuntary muscle contractions. HLA-DQ8, on the other hand, showed up in CRPS patients both with and without dystonia. This suggests that different forms of CRPS may have overlapping but distinct genetic profiles, and that the immune system is central to the genetic risk.
These HLA genes are the same family of genes involved in autoimmune conditions like type 1 diabetes and celiac disease. Their connection to CRPS supports the theory that an overactive or misdirected immune response is part of what drives the condition in genetically susceptible people.
Epigenetic Changes Add Another Layer
Beyond the DNA sequence you inherit, there’s another layer of biology called epigenetics. These are chemical modifications that sit on top of your genes and influence whether those genes get turned on or off. They can be shaped by environment, trauma, and life experiences.
A study comparing military personnel who developed CRPS after traumatic injury to those who developed other types of nerve pain found 48 sites across the genome where the chemical tagging of DNA differed between the two groups. In the CRPS group, most of these sites were “hypomethylated,” meaning the chemical tags that normally quiet gene activity were reduced. In practical terms, genes that should have been dialed down were instead more active.
The genes most affected were clustered in immune-related pathways: immune system activation, immune development, and the processing of molecules that help the body recognize threats. The gene with the single largest difference, HLA-DRB6, had already been linked to CRPS in earlier research. This reinforces that the immune system is a key player and suggests that trauma itself can alter gene activity in ways that tip the balance toward CRPS in some people.
CRPS vs. Inherited Pain Conditions
Part of the confusion around CRPS and heredity comes from its overlap with genuinely inherited pain syndromes. Mutations in a gene called SCN9A, which controls sodium channels in pain-sensing nerves, cause conditions like erythromelalgia (burning pain and redness in the extremities) that can look very similar to early-stage CRPS. SCN9A conditions follow a clear autosomal dominant inheritance pattern, meaning a child has a 50% chance of inheriting the mutation if one parent carries it.
CRPS does not follow this pattern. There is no single gene mutation that causes CRPS, and most people with CRPS do not have affected parents or children. The distinction matters because it shapes what “risk” actually means. If a parent has a SCN9A mutation, genetic testing can determine whether a child inherited it. With CRPS, there is no equivalent test. The genetic vulnerability appears to involve multiple genes, each contributing a small amount of risk, interacting with environmental triggers like injury or surgery.
What This Means for Your Risk
If you have a family member with CRPS, your risk is likely somewhat higher than the general population’s, but it’s far from certain that you’ll develop it. The genetic factors identified so far, like HLA-DQ8, are common in the general population too. Millions of people carry these variants and never develop CRPS. The condition seems to require a combination of genetic susceptibility, an appropriate trigger (usually physical trauma), and possibly epigenetic changes that amplify the immune response at the wrong time.
There is currently no genetic test that can predict whether someone will develop CRPS. The research is still working out which genes matter most and how they interact. What the evidence does tell us is that CRPS is not purely random. Biology loads the gun, but injury pulls the trigger. Having a family history is worth mentioning to your doctor if you’re recovering from surgery or a significant injury, as early recognition and treatment of CRPS leads to better outcomes.