AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Noonan SyndromeLEOPARD SyndromePhenotypeProtein Tyrosine Phosphatase, Non-Receptor Type 11GenotypeSOS1 ProteinSyndromeMutationCostello SyndromeFaciesDNA Mutational AnalysisLoose Anagen Hair SyndromePulmonary Valve StenosisEyebrowsMutation, Missenseras ProteinsFrasier SyndromeAbnormalities, MultipleFailure to ThriveProtein Tyrosine PhosphatasesCherubismSkin AbnormalitiesCraniofacial AbnormalitiesPedigreeEctodermal DysplasiaSexual DevelopmentBezoarsGerm-Line MutationHeart Defects, CongenitalGenes, Neurofibromatosis 1Leukemia, Myelomonocytic, JuvenileExonsNiemann-Pick DiseasesPolymorphism, GeneticDiagnostic Techniques, EndocrineGenetic Association StudiesNeurofibromatosis 1Cardiomyopathy, HypertrophicIntracellular Signaling Peptides and ProteinsAge of OnsetAllelesCodon, NonsenseMolecular Sequence Data
SOS1PTPN11BRAFCostelloCorrelationMutationLEOPARDCorrelationsMissenseHRASAutosomal dominantCardiofaciocutaneous syndromeSymptomsAbnormalitiesCongenital1963GenesLive birthsRASopathyDiagnosisClinicalMyeloproliferativeInfantsFrequentTurnerFacialFeaturesIncidenceCasesDistinctCharacteristicPatientsDeformityIndividualsPathway
SOS17
  • Missense pathogenetic variants of SOS1 gene are the second most common cause of Noonan syndrome (NS) and account approximately for 13% to 17% of cases. (biomedcentral.com)
  • Subjects carrying a pathogenetic variant in SOS1 gene tend to exhibit a distinctive phenotype that is characterized by ectodermal abnormalities. (biomedcentral.com)
  • we report two cases of newborns with CVG and phenotype suggestive for NS who have been diagnosed to harbour the same pathogenetic variant in SOS1 gene. (biomedcentral.com)
  • A study by Cessans et al comparing growth patterns in patients with Noonan syndrome based on genotype found that at birth, patients with PTPN11 mutations tended to be shorter and thinner than were those with mutations in SOS1 , KRAS , or Noonan syndrome with multiple lentigines-associated PTPN11 (NSML- PTPN11 ). (medscape.com)
  • in a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. (unifesp.br)
  • SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions. (lu.se)
  • Bidirectional sequencing analysis of PTPN11, SOS1, RAF1, BRAF, and MAP2K1 focused on exons carrying recurrent mutations, and of all KRAS exons were performed. (bvsalud.org)
PTPN1113
  • PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. (unifesp.br)
  • Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. (medscape.com)
  • Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. (lu.se)
  • A novel PTPN11 missense mutation in a patient with LEOPARD syndrome. (lu.se)
  • Hodgkin's lymphoma in a patient with Noonan syndrome with germ-line PTPN11 mutations. (lu.se)
  • Germline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors. (lu.se)
  • Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia. (lu.se)
  • Early fetal death associated with compound heterozygosity for Noonan syndrome-causative PTPN11 mutations. (lu.se)
  • Clonal duplication of a germline PTPN11 mutation due to acquired uniparental disomy in acute lymphoblastic leukemia blasts from a patient with Noonan syndrome. (lu.se)
  • Acquisition of JAK2, PTPN11, and RAS mutations during disease progression in primary myelodysplastic syndrome. (lu.se)
  • The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. (lu.se)
  • Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP) - pure coincidence? (genomeweb.com)
  • Different mechanisms of disease have been demonstrated to be associated with the two classes of PTPN11 mutations underlying Noonan syndrome and Noonan syndrome with multiple lentigines (also known as LEOPARD syndrome). (biomedcentral.com)
BRAF4
  • Mutations in KRAS , NRAS , BRAF , and MAP2K1 also have been identified, but in smaller numbers of patients. (medscape.com)
  • The BRAF , MAP2K1 , MAP2K2 , and KRAS genes provide instructions for making proteins that work together to transmit chemical signals from outside the cell to the cell's nucleus. (medlineplus.gov)
  • Some people with the signs and symptoms of cardiofaciocutaneous syndrome do not have an identified variant in the BRAF , MAP2K1 , MAP2K2 , or KRAS gene. (medlineplus.gov)
  • DISCUSSION: CFC patients showed a rather severe phenotype but at least one patient with BRAF mutation showed no developmental delay, which illustrates the variability of the phenotypic spectrum caused by BRAF mutations. (bvsalud.org)
Costello7
Correlation4
  • This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype-phenotype correlation. (unifesp.br)
  • Growth patterns of patients with Noonan syndrome: correlation with age and genotype. (medscape.com)
  • Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients. (bvsalud.org)
  • An exhaustive genotype-phenotype correlation was reported. (biomedcentral.com)
Mutation3
  • Whole exome sequencing identifies a novel splice-site mutation in ADAMTS17 in an Indian family with Weill-Marchesani syndrome. (genomeweb.com)
  • Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. (bvsalud.org)
  • In this manuscript, the authors described the mutation spectrum causally linked to Noonan syndrome (NS) (MIM PS163950) and clinically related disorders, and the associated clinical outcome, based on a pediatric cohort of 47 affected subjects. (biomedcentral.com)
LEOPARD2
  • OBJECTIVES: To describe 11 patients with cardiofaciocutaneous syndrome (CFC) and compare them with 130 patients with other RAS-MAPK syndromes (111 Noonan syndrome patients [NS] and 19 patients with LEOPARD syndrome). (bvsalud.org)
  • Consistent with their distinctive consequences on SHP2 function and signal transduction, these mutations do not cause NS but underlie Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome (MIM PS151100), a disorder similar but distinct from NS. (biomedcentral.com)
Correlations2
  • Genotype-phenotype correlations in Noonan syndrome. (lu.se)
  • Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. (bvsalud.org)
Missense1
  • We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. (bvsalud.org)
HRAS1
Autosomal dominant2
  • Noonan and Noonan-like syndromes are multisystem genetic disorders, mainly with autosomal dominant trasmission, caused by mutations in several genes. (biomedcentral.com)
  • Noonan syndrome occurs in either a sporadic or autosomal dominant fashion. (medscape.com)
Cardiofaciocutaneous syndrome8
Symptoms2
  • Skin signs and symptoms in Noonan syndrome include lymphedema (lymph swelling of the extremities), keloid formation, excessive scar formation, hyperkeratosis (overdevelopment of outer skin layer), pigmented nevi (darkly pigmented skin spots), and connective tissue disease. (wikipedia.org)
  • Treatment is focused on the symptoms of Noonan syndrome and may include cardiac therapy, growth hormone therapy, physical and speech therapy, ophthalmologic treatment, management of bleeding disorders, treatment of lymphatic problems, and urologic therapy (in males). (medscape.com)
Abnormalities2
  • Abnormalities in the limbs and extremities may occur in Noonan syndrome. (wikipedia.org)
  • Noonan syndrome (MIM: 163950) is characterised by postnatal short stature, distinctive facial features, congenital heart defects, variable degree of developmental delay and other structural abnormalities. (bmj.com)
Congenital6
  • Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. (wikipedia.org)
  • Noonan syndrome is the second most common syndromic cause of congenital heart disease. (wikipedia.org)
  • Noonan syndrome was first recognized as a unique entity in 1963, when Noonan and Ehmke described a series of patients with unusual facies and multiple malformations, including congenital heart disease. (medscape.com)
  • The primary source of morbidity and mortality in patients with Noonan syndrome depends on the presence and type of congenital heart disease. (medscape.com)
  • Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy. (genomeweb.com)
  • INTRODUCTION AND OBJECTIVES: Molecular characterization of congenital heart diseases now includes the not infrequent dysmorphic Noonan syndrome. (bvsalud.org)
19632
  • The condition was named after American pediatric cardiologist Jacqueline Noonan, who described her first case in 1963. (wikipedia.org)
  • [2] The condition was first described in 1883 and was named after American pediatric cardiologist Jacqueline Noonan, who described further cases in 1963. (handwiki.org)
Genes4
  • The pathophysiology of Noonan syndrome is not fully understood but is associated with mutations in genes that are part of the RAS/RAF/MEK/ERK signal transduction pathway, an important regulator of cell growth. (medscape.com)
  • Several other genes that have been linked to a Noonan syndrome-like phenotype have been recognized as well but have been found in a very small number of persons. (medscape.com)
  • Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. (unifesp.br)
  • To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. (unifesp.br)
Live births1
RASopathy1
  • Noonan syndrome is a type of RASopathy, the underlying mechanism for which involves attenuation of the RAS/MAPK cell signaling pathway. (wikipedia.org)
Diagnosis3
  • The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. (wikipedia.org)
  • Noonan syndrome: clinical features, diagnosis, and management guidelines. (medscape.com)
  • Although differential diagnosis between these two syndromes could be difficult, particularly in the first age of life, we underline the relevance in discriminating these two disorders in terms of affected signaling pathway to allow an effective targeted pharmacological treatment. (biomedcentral.com)
Clinical1
Myeloproliferative1
Infants1
Frequent1
  • Short stature, developmental delay, language difficulties and ectodermal anomalies were more frequent in CFC patients when compared with other neuro-cardio-faciocutaneous syndromes (P (bvsalud.org)
Turner1
  • The observation that patients with Noonan syndrome have normal karyotypes was important in allowing the distinction to be made between the Turner and Noonan syndromes. (medscape.com)
Facial2
Features4
  • Some of the characteristic features of Noonan syndrome include a large head with excess skin on the back of the neck, low hairline at the nape of the neck, high hairline at the front of the head, triangular face shape, broad forehead, and a short, webbed neck. (wikipedia.org)
  • Abnormal features of Noonan syndrome at the age of 3 months: Note the eyebrow slant and left-side eyelid dropping. (handwiki.org)
  • Abnormal features of Noonan syndrome at the age of 3 months: Note the low-set, posteriorly rotated, and abnormally formed ear. (handwiki.org)
  • About 25% of the individuals had Noonan-like features. (bvsalud.org)
Incidence1
Cases1
  • Fewer than 5 percent of cases are caused by variants in the KRAS gene. (medlineplus.gov)
Distinct1
  • Type V is considered as a distinct entity as, unlike the other types, is usually associated with both cystic renal disease and liver fibrosis (Caroli syndrome). (biomedcentral.com)
Characteristic1
Patients4
  • Bleeding diathesis is present in as many as half of all patients with Noonan syndrome. (medscape.com)
  • A study by Jongmans et al also demonstrated an elevated cancer risk in patients with Noonan syndrome. (medscape.com)
  • Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1. (genomeweb.com)
  • Whole genome sequencing reveals potential targets for therapy in patients with refractory KRAS mutated metastatic colorectal cancer. (genomeweb.com)
Deformity1
Individuals2
Pathway1