Updated September 29, 2026
Autoinflammatory diseases have a variety of causes. Some can be traced to a change in a single gene. Others reflect a more complicated interaction between genes and the environment. So when a family asks, “Is this genetic?” the answer is not always a simple yes or no.
When one gene makes a difference
Genes contain instructions for making proteins, including proteins that help control inflammation. Certain changes in these instructions can leave the immune system producing inflammation when it is not needed.
Examples include familial Mediterranean fever, associated with MEFV; cryopyrin-associated periodic syndromes, associated with NLRP3; and TRAPS, associated with TNFRSF1A. Everyone has these genes. What matters is the particular change, or variant, and how it affects the protein. FMF, NLRP3, TRAPS
But even people with the same disease-associated variant may have different symptoms. Some become ill early, others later, and some never develop the expected disease. Genes help explain the illness, but they do not always predict exactly how someone will feel. MedlinePlus: Why genetic conditions vary
Does genetic always mean inherited?
No. A disease-causing variant can be inherited from a parent, but it can also arise for the first time in a child. This is called a de novo variant.
Sometimes a variant is present in only some of a person’s cells, a situation called mosaicism. These possibilities help explain why a genetic condition can occur in someone with no family history of similar symptoms. MedlinePlus: Types of genetic variants
When several genes contribute
PFAPA and Behçet disease do not usually follow the same pattern as a single-gene disorder. Genetic differences can increase susceptibility without determining whether someone will develop the illness.
A 2020 study identified shared genetic susceptibility between PFAPA, Behçet disease, and recurrent mouth ulcers. That is an important clue about their biology. It does not mean there is a genetic test that can, by itself, diagnose PFAPA. Read the study
What can a genetic test tell you?
A genetic report needs to be interpreted alongside symptoms, examination findings, and other testing.
- A disease-causing result may help establish a diagnosis when it fits the person’s clinical picture and the condition’s inheritance pattern.
- A variant of uncertain significance, or VUS, means there is not enough evidence to know whether the change causes disease. It is not a confirmed diagnosis.
- A negative result means the test did not identify an explanation within its scope. It does not rule out every autoinflammatory disease.
Different tests examine different genes and types of changes. A specialist or genetic counselor can explain what was tested, what remains uncertain, and whether further evaluation would be useful. Understanding genetic test results
Useful questions include: Does this result explain my symptoms? Would it change treatment? Should anyone else in the family be tested? Could its interpretation change as we learn more?
Genetic testing can answer important questions. Sometimes it also gives us better questions to ask.