RASopathies: Evolving Concepts in Pathogenetics, Clinical Features, and Management

Abstract

RASopathies refers to the group of disorders which are caused by a mutation in various genes of the RAS/MAPK (RAT sarcoma virus/Mitogen activated protein kinase) pathway. It includes many genes with varied functions, which are responsible for cell cycle regulation. As the mutation in one gene affects the entire pathway, there are many overlapping features among the various syndromes which are included under an umbrella term “RASopathies.” However, neuroectodermal involvement is a unifying feature among these syndromes, which are caused by germline mutations affecting genes along this pathway. Recently, many other RASopathies have been described to involve blood vessels, lymphatics, and immune system. Also, many cutaneous mosaic disorders have been found to have mutations in the concerned pathway. The purpose of this article is to briefly review the pathogenesis of RASopathies with cutaneous manifestations, and summarise the features that can be helpful as diagnostic clues to dermatologists. As we understand more about the pathogenesis of the pathway at the cellular level, the research on genotype-phenotype correlation and therapeutic options broadens. Targeted therapy is in the clinical and preclinical trial phase, which may brighten the future of many patients.

Keywords

• newer drugs
• pathogenetics
• rasopathies