Li-Fraumeni syndrome

Li-Fraumeni syndrome is a rare autosomal dominant hereditary disorder that greatly increases susceptibility to cancer. The disorder is named after Frederick Pei Li and Joseph F. Fraumeni, U.S. physicians who originally described the syndrome.

While Li-Fraumeni syndrome is typically a rare disorder, a founder effect has resulted in 1 person in 375 from Southern Brazil carrying the R337H variant. Thus, unexpectedly, upwards of 300,000 Brazilians might be affected by this otherwise rare disease. [PMID 27663983] A screening program found 0.27% of newborns were carriers in the Southern Brazilian state of Paraná. [PMID 23733769]

The syndrome is most commonly caused by mutations in the p53 tumor suppressor gene TP53. Carriers are especially susceptible to brain tumors, breast cancer, leukemia, sarcoma of bone and soft tissues, and adrenal cortical carcinoma. Li-Fraumeni syndrome may be suspected in patients who develop a sarcoma before age 45, especially if any close relatives have also been diagnosed with cancer by that age or with a sarcoma at any age.

SNPs leading to Li-Fraumeni syndrome include:

• rs11540652, TP53 R248Q
• rs121912651, TP53 R248T
• rs121912652, TP53 E258K
• rs121912653, TP53 L252P
• rs121912656, TP53 G245D
• rs121912657, TP53 V272L
• rs121912664, TP53 R337H
• rs121912662, TP53 L344P
• rs121912663, TP53 K292I
• rs121912666, TP53 Y220S
• rs28934575, TP53 G245C
• rs28934576, TP53 R273H
• rs28934578, TP53 R175H
• rs28934873, TP53 M133T
• rs28934875, TP53 A138P