Familial PDGFRA-mutation syndrome: somatic and gastrointestinal phenotype.

Germline activating platelet-derived growth factor receptor alpha (PDGFRA) mutations have been described in four families. All the index patients have presented with multiple mesenchymal tumors of the gastrointestinal tract. We identified a fifth family with four first-degree relatives that harbor a PDGFRA exon 18 (D846V) germline mutation. The affected kindred have a unique phenotype including coarse facies and skin, broad hands and feet, and previously undescribed premature tooth loss. While the index patient presented with multiple small bowel inflammatory fibroid polyps (IFPs) and has a gastric gastrointestinal stromal tumor (GIST), no tumors have yet been identified in other family members. We describe the pathology, genetics, the incomplete penetrance and variable expressivity of the familial PDGFRA-mutation syndrome referencing the mouse knock-in Pdgfra model. We speculate on the role of the telocyte, a recently described CD34, PDGFRA+ stromal cell, in the development of inflammatory fibroid polyps and the somatic phenotype.