Phenotype

Noonan syndrome

Biology

Gene

Costello syndrome

Mutation

MAPK/ERK pathway

Signal transduction

KRAS

PTPN11

Genetics

Medicine

American Journal of Medical Genetics Part C Seminars in Medical Genetics

RASopathies comprise a group of clinically overlapping developmental disorders caused by genetic variations affecting components or modulators of the RAS‐MAPK signaling cascade, which lead to dysregulation of signal flow through this pathway. Noonan syndrome and the less frequent, clinically related disorders, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan syndrome‐like disorder with loose anagen hair are part of the RASopathy spectrum and share a recognizable pattern of multisystem involvement. This review describes the “Noonan syndrome‐like” phenotype as a common phenotypic signature of generalized developmental RAS pathway dysregulation. Distinctive features of the different entities are revisited against the background of the understanding of underlying genetic alterations and genotype correlations, which has evolved rapidly during the past 20 years, thereby leading to suggestions regarding the nosology of RASopathies.

Clinical overview on <scp>RASopathies</scp>

Clinical overview on RASopathies