Multidisciplinary Treatment of Patients With Noonan Syndrome

Importance Noonan syndrome (NS) is a rare developmental disorder and the most common condition among the RASopathies. Diagnosis and treatment of NS can be challenging due to the wide phenotypic variability of its manifestations. A multidisciplinary approach is essential, with continuous care required from infancy through adulthood; however, there is a lack of updated and widely shared guidelines for treating this condition. Objective To develop consensus statements on the diagnosis of NS, patient transition from pediatric to adult care, follow-up, and treatment of short stature with recombinant human growth hormone (rhGH). Evidence Review Consensus was achieved through a modified Delphi process involving a multidisciplinary steering committee comprising 3 pediatric endocrinologists, 1 pediatric cardiologist, 1 molecular geneticist, along with a 25-member expert panel who had expertise in treating NS at clinical reference centers in Italy. In December 2023, the steering committee drafted 47 statements based on published evidence and clinical experience. These statements were then submitted to the expert panel, which provided anonymous feedback on their level of agreement or disagreement between January and March 2024. Findings All 25 members of the expert panel completed the Delphi survey and consensus was achieved on all statements after the first round of voting. Full agreement (100%) was reached on several key points: importance of molecular characterization for diagnosis, prognosis, and treatment decisions; necessity of a multidisciplinary approach to NS treatment; need for improved transition from pediatric to adult care; increased risk in patients with hypertrophic cardiomyopathy (HCM); importance of monitoring adherence to rhGH therapy; acknowledgment that partial GH insensitivity should not exclude rhGH therapy; and safety concerns regarding rhGH therapy, particularly related to HCM and the risk of malignant neoplasms. Conclusions and Relevance Effective treatment of NS requires a multidisciplinary and personalized approach from infancy through adulthood. This comprehensive set of consensus statements is intended for clinicians to implement more effective care of patients with NS.