Evaluation of social deprivation as a modifier of phenotypic divergence in PTEN Hamartoma Tumor Syndrome

Pathogenic mutations in phosphatase and tensin homolog ( PTEN ), a tumor suppressor gene, leads to the development of PTEN Hamartoma Tumor Syndrome (PHTS). Patients carry significantly increased risks for cancer and neurodevelopmental disorders such as autism spectrum disorder (ASD). The factors which modify PTEN function and drive PHTS phenotype remain unknown. Social determinants of health are increasingly being identified as important regulators of disease pathogenesis. Here, we conduct a retrospective cross-sectional study to evaluate the association between social deprivation, as measured by area deprivation index (ADI), and neurodevelopmental versus cancer phenotypes in patients with PHTS. Our findings suggest ADI alone is not associated with PHTS phenotype, and that its divergence is likely multifactorial in nature. More broadly, our study highlights the importance of integrating environmental pressures with genetic risk modification in the study of complex human disease. • It is important to consider the role of social deprivation in complex disease • Evaluation of social deprivation in the context of genetic predisposition • Social deprivation is not associated with PHTS phenotype (cancer, ASD) • Social deprivation alone is unlikely to modify mutant PTEN function or its protein • Phenotypic divergence of PHTS is multifactorial and requires further investigation