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.

List of RASopathies

Known RASopathies include the following:

• 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. Generally, RASopathies increase the risk of developing cancers. Neurodevelopmental or psychiatric disorders such as attention deficit hyperactivity disorder, autism spectrum disorder, and anxiety occur at higher rates in individuals with RASopathies.

Genetics

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:

• HRAS
• KRAS
• NRAS
• RRAS
• RIT1
• NF1
• RASA1
• RASA2
• SYNGAP1
• SOS1
• SOS2
• CBL
• PTPN11
• BRAF
• RAF1
• MAP2K1
• MAP2K2
• MAP3K8
• SPRED1
• SPRY1
• MYST4
• LZTR1
• A2ML1