Genomic alterations and genetic testing

Somatic gain-of-function PDGFRB variants have been identified in sporadic cases of infantile myofibromatosis, including activating single nucleotide variants and in-frame indels and duplications.[14,15] PDGFRB variants are observed in most cases with multicentric nodules, but are less common in cases with solitary myofibroma.[15,16] Some PDGFRB variants that cause infantile myofibromatosis are sensitive to tyrosine kinase inhibitors like imatinib.[15,16]

An inherited autosomal dominant form of infantile myofibromatosis has been described. It is associated with germline pathogenic variants of the PDGFRB gene, with the R561C variant being most commonly observed.[17-19] The R561C variant is a relatively weak activator of PDGFRB, which may explain the presence of additional PDGFRB variants with stronger activity in some familial infantile myofibromatosis cases.[16,17]

The European Society for Paediatric Oncology Host Genome Working Group developed counseling and germline testing guidelines for these groups of children. This group recommends germline analysis for children with infantile myofibromatosis who have at least one of the following criteria:[20]