European network on Noonan Syndrome and related disorders – NSEuroNet

A group of disorders caused by dysregulation of the RAS-MAPK signaling pathway has emerged. These rare disorders have overlapping features including reduced growth, facial dysmorphia, cardiac disease, variable cognitive deficits, and predisposition to specific malignancies. While research has provided insights into the molecular basis of these diseases, there are questions about pathogenesis that remain unanswered. This is due to the multifaceted biology of RAS signaling and the genetic heterogeneity underlying these disorders. Moreover, since the wide clinical spectrum and overlap of these conditions, a significant proportion of subjects does not have diagnosis and management is often slanted. Our goals are to explore further the disease pathogenesis by identifying novel disease genes and understand the molecular and cellular mechanisms involved, provide molecular epidemiology data, delineate genotype-phenotype correlations, and translate this information to the clinic by making available diagnostic and experimental tools to favor early diagnosis and development of novel therapies. Diagnostic criteria and molecular knowledge will be integrated to produce flow-charts for a decision-making support to clinicians. The studies proposed in this interdisciplinary network are required for effective and early diagnosis, and patient management and counseling, and will guide work directed to ameliorate aspects of these diseases, such as hypertrophic cardiomyopathy, reduced growth, predisposition to malignancies and cognitive impairments.