Current opinions on Noonan syndrome and RASopathies

Purpose of review Noonan syndrome and related disorders (RASopathies) affect ~1 in 2000 individuals and are associated with a wide range of phenotypic manifestations. It is highly likely that pediatricians and other pediatric subspecialists will encounter multiple patients with these diagnoses in their clinical practice. It is important that pediatric providers recognize common diagnostic features and are informed regarding recent advances in diagnosis and emerging treatment options for patients with these conditions. Recent findings Major themes of research articles published about RASopathies in the past 18 months include the utilization of pathway targeted drugs such as trametinib for treatment-refractory cardiac and lymphatic manifestations, emerging genotype–phenotype correlations, and detailed characterization of neurologic manifestations. Summary The potential for pathway targeted therapy, with increasing reported use of trametinib for severe cardiac and lymphatic manifestations of RASopathies, exemplifies the importance of recognizing RASopathy diagnoses and of clearly defining natural history and treatment endpoints. Further refinement of genotype–phenotype correlations and the phenotypic spectrum, particularly the delineation of neurologic manifestations clinically and radiographically, are likely to be areas of significant knowledge growth in upcoming years.