Cohort study and systematic review reveals distinct solid tumour risks across RASopathies, highlighting the need for syndrome-specific cancer surveillance.
Key Points
To determine the prevalence, spectrum, and genotype-phenotype correlations of solid tumours across different RASopathies.
Evaluated solid tumour prevalence and clinical spectrum in a single-centre cohort of individuals with RASopathies (n=138), excluding neurofibromatosis type 1.
Integrated cohort data with a systematic literature review to examine tumour distribution patterns and gene-specific risk variants.
Solid tumours occurred in 10.8% of individuals with Noonan syndrome (5.4% malignant), 47.8% with Costello syndrome (30.4% malignant), and 7.3% with cardiofaciocutaneous syndrome (2.4% malignant).
Costello syndrome showed the greatest tumour burden, characterized predominantly by multiple primary bladder tumours, whereas Noonan syndrome presented mainly with low-grade central nervous system tumours linked to PTPN11 variants.
Median age at tumour diagnosis was 19 years in Noonan syndrome, 14 years in Costello syndrome, and 13 years in cardiofaciocutaneous syndrome, with risk variants identified in HRAS, PTPN11, and SOS1.