[Rasopathies: developmental disorders that predispose to cancer and skin manifestations]

Area of Science:

• Molecular Biology
• Genetics
• Developmental Biology

Context:

• The RAS/mitogen-activated protein kinase (MAPK) pathway regulates crucial cellular functions like proliferation and survival.
• Somatic mutations in this pathway are implicated in approximately 30% of human cancers.
• Germline mutations lead to a spectrum of developmental abnormalities known as rasopathies.

Purpose:

• To highlight the significance of germline mutations in the RAS/MAPK pathway.
• To underscore the clinical heterogeneity and shared features of rasopathies.
• To emphasize the diagnostic utility of recognizing cutaneous manifestations in rasopathies.

Summary:

• Germline mutations in the RAS/MAPK pathway cause rasopathies, a group of genetic syndromes with diverse clinical presentations.
• Affected individuals often exhibit developmental delays, cardiac defects, dysmorphic features, and skin anomalies.
• Specific syndromes include Noonan syndrome, Costello syndrome, neurofibromatosis-1, LEOPARD syndrome, cardiofaciocutaneous syndrome, and Legius syndrome.

Impact:

• Facilitating earlier and more accurate diagnosis of rasopathies through recognition of skin findings.
• Improving clinical management and genetic counseling for affected individuals and families.
• Enhancing understanding of genotype-phenotype correlations within RAS/MAPK pathway-related disorders.