Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status

Abstract Background Costello syndrome (CS) and cardio-facio-cutaneous (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due their rarity, characterization musculo-skeletal phenotype in both has been poorly characterized. Patients methods Herein we reported data on orthopedic findings functional status large sample CS CFCS patients. Thirty-four patients (CS = 17 17) were recruited. Functional disability evaluations performed by assessing 6-min walking test (6MWT) Pediatric Outcomes Data Collection Instrument (PODCI). Genotype/phenotype correlation was also provided. Results Orthopedic manifestations are highly prevalent overlap two disorders. Overall, harboring recurrent HRAS Gly12Ser substitution show more severe compared carrying Gly12Ala Gly13Cys variants. Among patients, those MAP2K1/2 variant different characteristics BRAF variants, higher prevalence abnormalities. assessment showed that reached lower values general population, displaying lowest scores. Conclusions appear universal features they can evolve across patients’ life. Longitudinal using 6MWT PODCI could be useful evaluate impact outcome help planning tailored treatment these comorbidities.