Neurofibromatosis Type 1 (NF1) is a neurocutaneous syndrome characterized by multiple café-au-lait macules, neurofibromas, and predisposition to malignancies, including rhabdomyosarcomas (RMS). Somatic NF1 mutations occur in RMS and other cancers, and ∼1% of patients with RMS have NF1. We describe three patients who presented prior to one year of age with RMS and were subsequently diagnosed with NF1. Compared to sporadic RMS, patients with this cancer predisposition syndrome are diagnosed younger, genitourinary sites are more common, and tumors are almost exclusively the embryonal subtype. Genomic sequencing of the tumor was initiated in one patient, and we identified a second sequence variant in NF1. The identification of molecular drivers in tumors is changing the nature of pediatric oncology by informing therapeutics targeted to specific molecular pathways and selecting patients who are likely to harbor germline variants in cancer predisposition genes who would benefit from a Medical Genetics assessment.
Keywords: Genetics; Neurofibromatosis Type 1; rhabdomyosarcoma.