For many people diagnosed with systemic mastocytosis (SM), one question quickly follows: Could my children or relatives develop this, too? The vast majority of SM cases are driven by genetic mutations, so it only seems natural to wonder if it runs in families.
The reassuring reality is that, in most cases, SM is not inherited. Although genes play a central role in the disease, the key mutation typically develops during a person’s lifetime rather than being inherited.
The role of genetic mutations
Most cases of SM are linked to a mutation in the KIT gene, which plays an important role in controlling how mast cells grow and survive. Specifically, the KIT D816V mutation causes mast cells to grow uncontrollably and accumulate in the body.
Learn more about SM causes and risk factors
However, this mutation is almost always acquired, not inherited. Known as a somatic mutation, it develops during a person’s lifetime rather than being passed down from parent to child. Somatic mutations occur in certain cells after conception and are not present in every cell of the body.
Are inherited cases of SM possible?
While most cases of SM are sporadic, some studies have documented families in which multiple relatives have mastocytosis. These cases are extremely uncommon and often involve slightly different genetic changes than the typical KIT mutation seen in most patients.
As a result, researchers are increasingly focused on genetic susceptibility rather than direct inheritance. One area of focus is hereditary alpha-tryptasemia (HαT), an inherited trait caused by extra copies of the TPSAB1 gene that leads to higher baseline tryptase levels.
Studies show HαT appears more frequently in people with SM than in the general population, suggesting that it may increase the likelihood of developing mast cell disease or influence how it presents. In other words, a person might inherit a predisposition, but not the disease itself.
What this means for families
For the vast majority of people with SM, the risk to children or siblings is considered very low. Genetic testing for family members is not routinely recommended unless there is a clear pattern of mast cell disease across multiple relatives.
This can be reassuring news for many individuals who worry about passing the condition on. Still, anyone with concerns about family risk may benefit from speaking with a genetic counselor or specialist familiar with mast cell disorders.
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