Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

RASopathies (Neuro-Cardio-Facial-Cutaneous Syndrome) - Overview

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

The “RASopathies” is the term for a clinically and genetically heterogeneous group of disorders that are caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated-protein kinase pathway. The Ras/MAP kinase signaling pathway plays an essential role in the regulation of the cell cycle, differentiation, growth and apoptosis; processes which are crucial for normal development. Dysregulation of this pathway has a profound impact on development. Most mutations causing the syndrome are activating changes which increase signal transduction within this pathway.

Diseases categorized as “RASopathies” and their causative genes are listed below. Details on each disease can be found in the respective entry.

Each of these syndromes has its clinical characteristics. Several organ systems (integumentary, cardiovascular system, musculoskeletal system, gastrointestinal tract, CNS, eye) are affected. Some syndromes are characterized by certain craniofacial features; some are marked by an increased risk for tumors. The syndromes overlap significantly in there signs and symptoms, which may complicate establishing a clear diagnosis and targeted diagnostic procedures. Moreover, several of these disorders may be caused by mutations in various genes of the Ras/MAPK pathway.