- Has been diagnosed with a sarcoma before the age of 45 years.
- Has a first-degree relative with any type of cancer who was also diagnosed before age 45.
- Has a third family member (first- or second-degree relative) with a cancer diagnosis in a similar timeline, or a sarcoma at any age. The third member must also be in the same familial lineage as the primary and secondary family members.
LFS affects both pediatric and adult populations. Osteosarcoma is the most common malignancy in children (30%), and breast cancer is the most common in adults (79% of women with LFS). LFS shows heterogeneity in terms of age of onset and type of malignancy.
Geographically, LFS is highly prevalent in Brazil due to a founder effect mutation. Many individuals of Brazilian descent with LFS have a specific TP53 mutation (p.R337H) that predisposes these individuals to adult papillary thyroid cancer, renal cancer, and lung adenocarcinoma, more so than other carriers of the TP53 gene. This may suggest a variant form of LFS.