Noonan syndrome is an autosomal dominant disorder that is both phenotypically and genetically heterogeneous. It is characterized by short stature, congenital heart defects (especially pulmonic stenosis [narrowing of the pulmonary valves] and hypertrophic cardiomyopathy), a broad or webbed neck, chest wall deformities, and varying degrees of intellectual disability. Lymphatic problems (often beginning prenatally), bleeding disorders (such as difficulties with clotting and easy bruising), undescended testes, hearing deficits, and failure to thrive are also common among individuals with this condition. In addition, individuals with Noonan syndrome generally have a characteristic facial appearance that changes with the age of the patient, but often includes widely spaced eyes that are down-slanting, ptosis (drooping eyelids), and low-set and posteriorly rotated ears. Noonan syndrome, which is believed to affect between 1 in 1000 and 1 in 2500 individuals, is now known to be part of a clinical continuum associated with hyperactive RAS (rat sarcoma viral oncogene) signaling. Syndromes with features and a pathogenesis overlapping those of Noonan syndrome include cardiofaciocutaneous (CFC) syndrome, LEOPARD syndrome, and Costello syndrome. All four disorders result from deleterious variants in genes known to be involved in the RAS/mitogenactivated protein kinase (MAPK) pathway. Variants in many genes have been detected in patients with Noonan syndrome, including the following: protein tyrosine phosphatase, non-receptor type 11 (PTPN11); Son of Sevenless, homolog 1 (SOS1); Kirsten rat sarcoma viral oncogene (KRAS); neuroblastoma rat sarcoma viral oncogene (NRAS); murine leukemia viral oncogene homolog 1 (RAF1); murine sarcoma viral oncogene homolog B1 (BRAF); suppressor of clear, homolog 2 (SHOC2); and MAPK/extracellular signal-regulated kinase (ERK) kinase 1 (MEK1). PTPN11 gene variants are by far the most common, accounting for approximately 50% of Noonan syndrome cases. Variants associated with Noonan syndrome are inherited in an autosomal dominant manner. Therefore, each child of an affected individual has a 50% chance of inheriting the causative variant and having the condition. While many individuals with Noonan syndrome have an affected parent, a significant proportion of cases are sporadic, resulting from a de novo gene variant in one of the causative genes.