J Genet Med.  2019 Jun;16(1):1-9. 10.5734/JGM.2019.16.1.1.

Noonan syndrome and RASopathies: Clinical features, diagnosis and management

• Lee BH
• Yoo HW

• KMID: 2451619
• DOI: http://doi.org/10.5734/JGM.2019.16.1.1

Abstract

Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40-50%), SOS1 (10-20%), RAF1 (3-17%), and RIT1 (5-9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.

Keyword

Noonan syndrome; Noonan syndrome related disorders; Genes

MeSH Terms

Congenital Abnormalities
Costello Syndrome
Diagnosis*
Ectoderm
Electrocardiography
Genitalia
Genotype
Heart Diseases
Humans
Hypertelorism
Intellectual Disability
Lentigo
Noonan Syndrome*
Panthera
Protein Kinases
Puberty, Delayed
Pulmonary Valve Stenosis
Thorax
Protein Kinases