When do you evaluate or refer for a cancer predisposition syndrome in a young child diagnosed with a sarcoma?

There are a number of hereditary cancer syndromes associated with development of sarcoma in children, including Li-Fraumeni syndrome (LFS), DICER1 syndrome, Constitutional Mismatch Repair Deficiency (CMMRD), Neurofibromatosis 1, hereditary retinoblastoma, Beckwith Wiedemann syndrome, the RASopathies, and Costello syndrome, among others. Recent evidence has revealed other new and possible associations such as Hereditary Breast and Ovarian Cancer (Li et al., PMID 33372952).

Cancer predisposition can be considered in a child with sarcoma based on the presence of various features such as 1) young age (young age is more often but not always associated with hereditary cancer); 2) positive family cancer history (presence of multiple individuals wi...

I would say if there is any question, just reach out to your local or regional Cancer Predisposition Program and ask. Additionally, there is MIPOGG (https://mipogg.com), an app that provides a fairly sophisticated approach to deciding if someone should be referred for genetic testing, or at least a genetic evaluation. There are some common threads like 2+ primary tumors, a family history of the same or related types, dysmorphic features, much earlier than expected age of onset, etc. Also, there are things like pathology details, as RMS with anaplasia is frequently associated with Li-Fraumeni Syndrome. However, MIPOGG starts with the type of tumor (Liquid, Solid, Neuro) and then goes into subtypes from there, and then asks additional questio...

Also consider enrollment in the Children's Oncology Group (COG) project for every child with molecular characterization initiative (MCI), for children with rhabdomyosarcoma, soft tissue sarcoma, and osteosarcoma (Ewing to come hopefully soon). This will give you paired tumor-germline testing on an exome backbone and as a first pass will most likely identify clear-cut pathogenic, likely pathogenic variants in a variety of cancer-related genes.