RASopathy

The RASopathies are a group of developmental syndromes caused by germline mutations in genes belonging to the Ras/MAPK pathway. Common features include intellectual disability, congenital heart defects, skin abnormalities, and craniofacial abnormalities.^[1]

Known RASopathies include the following:^[1][2]

• Capillary malformation-AV malformation syndrome (CV-AVM)
• Cardiofaciocutaneous syndrome (CFC)
• Neurofibromatosis type I (NF1)
• Noonan syndrome (NS)
• Costello syndrome (CS)
• Legius syndrome, also known as NF1-like syndrome
• Noonan syndrome with multiple lentigines (NSML), formerly called LEOPARD syndrome
• SYNGAP1-related intellectual disability

Somatic mutations in the Ras/MAPK pathway can cause cancers and disorders such as RAS-associated autoimmune leukoproliferative disorder (RALD) or juvenile myelomonocytic leukemia (JMML). These syndromes may share some features with RASopathies but are not considered true RASopathies if caused by somatic mutation.^[3] Generally, RASopathies increase the risk of developing cancers.^[1][4] Neurodevelopmental or psychiatric disorders such as attention deficit hyperactivity disorder, autism spectrum disorder, and anxiety occur at higher rates in individuals with RASopathies.^[5][6]

RASopathies are caused by germline mutations which result in overall activation of the Ras/MAPK pathway. Mutations in the following genes are associated with one or more types of RASopathy:^[2][7]