Children with systemic mastocytosis (SM) were more likely to carry serious genetic mutations beyond the well-known KIT D816V, a new study published recently in the British Journal of Haematology showed.
These results offer fresh insights into the biology of this rare condition. However, the long-term effects of these mutations remain unclear, and most children, regardless of mutation status, had stable or improving symptoms after years of follow-up.
Mastocytosis is a group of disorders caused by the buildup of abnormal mast cells, which are part of the immune system. In children, the disease typically affects only the skin (cutaneous mastocytosis), but some develop SM, where mast cells spread to internal organs.
“[T]his is the first study to evaluate a comprehensive panel of genes associated with myeloid disorders in paediatric mastocytosis across different disease subtypes,” explained this study’s authors.
Read more about SM causes and risk factors
In this study, researchers analyzed blood samples from 69 children, including 42 with SM and 27 with cutaneous disease. Using advanced genetic sequencing, they discovered 64 non-KIT mutations in genes tied to blood cell development.
KIT D816V, a well-established mutation linked to SM in adults, was found exclusively in children with SM, while other KIT gene changes, such as D419del and G565V, were limited to those with skin-only disease. Overall, 15 children had mutations labeled pathogenic or likely pathogenic, and nearly 87% of those children had systemic disease. These harmful mutations were not detected in genes typically associated with poor outcomes in adults, such as SRSF2 or ASXL1.
While these results may sound concerning, the real-world impact was limited. After a median of 10 years of follow-up, most children, especially those with cutaneous disease, had stable or improved symptoms. None of the children with skin-only disease developed SM. Even among those with SM, serious progression was rare, and some children showed reduced levels of the KIT D816V mutation over time.
For patients and families, these results are reassuring. Although more genetic changes are being discovered, they do not yet appear to strongly affect how the disease behaves in most children. Researchers emphasize the need for long-term monitoring, but these results support the generally mild course of pediatric mastocytosis and raise the possibility of using genetic testing to better understand individual risk in the future.
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