Multidimensional Assessment of the Impact of Li-Fraumeni Syndrome on Patients in Educational and Pedagogical Settings: From Molecular to Psychosocial Aspects*

Abstract Li-Fraumeni syndrome (LFS) is a rare hereditary cancer predisposition syndrome caused by mutations in the TP53 gene. It presents a clinical challenge due to its wide phenotypic variability and significant psychosocial implications for affected individuals and their families. To improve the identification, management, and follow-up strategies for LFS, with a focus on enhancing genetic counseling practices in a public health context. The present cross-sectional case study applied a mixed-methods approach to evaluate a Brazilian family with one index case clinically diagnosed with LFS, along with three first-degree relatives. Genetic analyses were conducted using in-silico tools to identify pathogenic variants. Validated questionnaires assessed psychological and social impacts on family members. Genetic testing identified a pathogenic TP53 variant (c.586C > T) in the index patient, reported for the first time in Brazil. The three first-degree relatives tested negative. Psychosocial evaluation revealed emotional stress, uncertainty about the future, and heightened concerns regarding hereditary cancer risk, particularly for younger family members. Early identification and close follow-up of individuals with LFS are essential to guide timely interventions. The findings support the development of more effective genetic counseling strategies tailored to affected families, contributing to public health initiatives and precise medical efforts.