Noonan syndrome

Abstract

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments.

Neuropsychological Functioning in Individuals with Noonan Syndrome: a Systematic Literature Review with Educational and Treatment Recommendations

“…Rarer gene mutations, including those in NRAS, KRAS, RIT1, RAF1, SCHOC2, and CBL, account for relatively few cases of NS (Aoki et al 2013;Roberts et al 2013). Studies reporting on individuals with RAF1 mutations typically find that intellectual and adaptive functioning is commensurate with individuals with other NS gene mutations (Cesarini et al 2009;Pierpont et al 2010b;Alfieri et al 2014).…”

“…Hearing and visual concerns are also common (Qiu et al 1998;Alfieri et al 2008). Comprehensive reviews of medical features in NS were recently published by Romano et al (2010) and Roberts et al (2013). A consensus statement on clinical management guidelines is available online (Noonan Syndrome Guideline Development Group 2010).…”

Update on the Diagnosis and Management of Inherited Aortopathies, Including Marfan Syndrome

“…A number of other genetic syndromes have been reported in association with aortic disease, including but not limited to: Weill-Marchesani syndrome (ADAMTS10 and FBN1) [13]; congenital contractural arachnodactyly (resembles MFS, is characterised by crumpled ears, scoliosis, joint contractures and FBN2 mutations) [14]; Noonan syndrome (mutations in the RAS-MAPK signalling pathway) [15,16]; Alagille syndrome (JAG1) [17] ; X-linked dominant periventricular nodular heteropia, EDS variant (FLNA) [18] and Shprintzen-Goldberg syndrome (SK1) [19].…”

Co‐occurrence of hypertrophic cardiomyopathy and juvenile myelomonocytic leukemia in a neonate with Noonan syndrome, leading to premature death

“…Noonan syndrome (NS) is an autosomal‐dominant disease characterized by distinctive facial dysmorphism, congenital heart disease (CHD), hypertrophic cardiomyopathy (HCM), short stature, webbed neck, cryptorchidism, skeletal abnormalities, and hematologic disorders1, 2 Recent evidence revealed that gain‐of‐function germline mutations affecting components of the RAS‐mitogen‐activated protein kinase (MAPK) signaling pathways are involved in NS. PTPN11 mutations (40%‐50%), SOS1 mutations (10%‐20%), RAF1 (3%‐17%), and RIT1 (9%) are common, followed by KRAS , NRAS , BRAF , SHOC2 , MAP2K1 , CBL, LZTR1, SOS2, RRAS, and CDC42 1, 2, 3, 4, 5, 6, 7, 8, 9…”

“…PTPN11 mutations (40%‐50%), SOS1 mutations (10%‐20%), RAF1 (3%‐17%), and RIT1 (9%) are common, followed by KRAS , NRAS , BRAF , SHOC2 , MAP2K1 , CBL, LZTR1, SOS2, RRAS, and CDC42 1, 2, 3, 4, 5, 6, 7, 8, 9…”