Quando pensare alla sindrome di Noonan

Noonan syndrome is a pleomorphic genetic disorder that causes cardiovascular involvement in a high percentage of affected individuals. Care includes attentiveness to several comorbidities, some directly impacting cardiac management (bleeding diatheses and lymphatic anomalies). More than 50% of patients with Noonan syndrome harbour PTPN11 pathogenic variation, which results in hyperactivation of RAS/ mitogen-activated protein kinase signalling. Molecular diagnosis with gene resequencing panels is now widely available, but phenotype variability and, in some cases, subtlety still make Noonan syndrome difficult to be diagnosed. Until genetic testing becomes universal for patients with congenital heart disease, alertness to the broad clinical presentations of Noonan syndrome remains crucial. Genotype-phenotype associations for Noonan syndrome enable better prognostication for affected patients when a molecular diagnosis is established. Noonan syndrome-specific treatment is still lacking; however, newly developed anticancer RAS pathway inhibitors might fill that gap if safety and efficacy can be established for indications such as pulmonary valve stenosis.