Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies

Study Description:\<TAB\> The RASopathies are a clinically defined group of disorders caused by pathogenic germline variants in genes encoding components of the Ras/mitogen-activated-protein kinase (Ras/MAPK) pathway. These disorders have overlapping clinical features due to Ras/MAPK dysfunction, including a predisposition to the development of certain malignancies. The aims of this prospective longitudinal cohort study are to determine the incidence of malignancy in patients with RASopathies and determine the underlying differences in those who develop tumors as compared to those who do not, in order to inform cancer screening recommendations. In addition, this longitudinal cohort study will provide a better understanding of non-tumor RASopathy manifestations. Objectives: Primary Objectives: * To establish a longitudinal cohort of participants with a clinical diagnosis of a RASopathy and/or a pathogenic germline variation in a Ras/MAPK pathway gene (excluding NF1). * To study the lifetime rates of cancer development in participants with a RASopathy. * To longitudinally characterize germline RASopathy-related tumor and non-tumor clinical manifestations. Secondary Objectives: * To create a biospecimen repository of carefully annotated tissue samples for use in subsequent etiologically oriented translational research projects. * To describe novel phenotypes associated with germline Ras/MAPK pathway genetic variation. Endpoints:\<TAB\> * Number of participants meeting enrollment criteria for inclusion in the RASopathy cohort. * Development of RASopathy-associated neoplasms in patients with RASopathies other than neurofibromatosis type 1 (NF1). * Longitudinal standardized quantitative evaluations of specific RASopathy manifestations.