Aggressive Systemic Mastocytosis Related to Germline p.D816V KIT Mutation

Systemic mastocytosis (SM) in adults is, in most cases, caused by a somatic mutation leading to p.D816V in KIT. We report the first proof of this variant as a heterozygous de novo germline mutation in a female infant with severe neonatal SM. The girl presented prenatally with hepatosplenomegaly and postnatally with diffuse cutaneous lesions and organ dysfunction. Histopathologic specimens displayed infiltration with atypical mastocytes. Molecular analyses confirmed the KIT mutation in multiple non-infiltrated tissues, demonstrating the germline nature of the mutation. Despite targeted treatment with pharmacokinetically monitored midostaurin and adjunct therapies, the disease progressed rapidly, resulting in fatal multiorgan failure.