There is limited research on function in individuals with RASopathies. Our hypothesis was that there was function and disability differences between Costello syndrome (CS) and Cardiofaciocutaneous syndrome (CFCS). The purpose of this study was to describe and compare the functional performance and level of disability of children with CS and CFCS using the Pediatric Outcomes Data Collection Instrument (PODCI) and Pediatric Evaluation of Disability Index (PEDI). Parents of individuals with a medical diagnosis of CS and CFCS completed the computer or paper version of the questionnaires. Comparisons of response data were made between the two syndromes and published normative data. Fifty-two parents participated in the study, 38 in the CS group and 14 in the CFCS group. There were no significant differences in PODCI or PEDI scores between the CS and CFCS groups. There were statistically significant differences from normative values for all PODCI domains (P ≤ 0.012). The PEDI T-scores of both groups were greater than two standard deviations below normative scores in mobility (CS = 12.37, CFCS = 2.37), social (CS = 24.01, CFCS = 20.08), and activity (CS = 15.88, CFCS = 14.32). Responsibility T scores were in the normal range (30-70) for the CS group (31.38), but not for the CFCS group (28.40). The CS and CFCS groups had activity limitations in the PODCI domains of upper extremity function, transfers, and mobility, sport and physical function. These functional limitations cause significant disability in the PEDI domains of daily activity, mobility, and socialization and cognition. CS and CFCS are similar conditions in respect to functional limitations and severity of disability.