AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and Processes
Noonan SyndromeLEOPARD SyndromeSOS1 ProteinProtein Tyrosine Phosphatase, Non-Receptor Type 11SyndromeGenes, DominantCostello SyndromeSOS Response (Genetics)FaciesLoose Anagen Hair SyndromePulmonary Valve StenosisEyebrowsAbnormalities, MultiplePolycystic Kidney, Autosomal DominantMutationPedigreeFailure to ThriveCherubismProtein Tyrosine PhosphatasesEctodermal DysplasiaCraniofacial AbnormalitiesSkin AbnormalitiesMutation, MissensePhenotypeDNA Mutational AnalysisGerm-Line MutationGenes, Neurofibromatosis 1Sexual DevelopmentBezoarsHeart Defects, CongenitalNeurofibromatosis 1Leukemia, Myelomonocytic, Juvenileras ProteinsDiagnostic Techniques, EndocrineCardiomyopathy, HypertrophicIntracellular Signaling Peptides and Proteins
RecessiveMutationsRAF1Features of Noonan syndrome includeCongenitalMutationGeneGenesMultisystemic disorderClinicalDiagnosisMental retardationLZTR1DisorderRasopathiesRASopathyLymphedema1963MyelodysplasticSymptomsWebbed neckMalignanciesCharacteristicsAbnormalTurnerDiseaseCancersOccurVariantPatientsFormForms
Recessive11
  • BACKGROUND: Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder that affects 1/200,000 to 1/1,000,000 children. (bvsalud.org)
  • the classical form is caused by autosomal recessive mutations of the WFS1 gene, and a smaller portion of patients has mutations in the CIDS2 gene, which are responsible for autosomal recessive Wolfram syndrome 2. (bvsalud.org)
  • To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. (bvsalud.org)
  • NS caused by pathogenic variants in LZTR1 can be inherited in either an autosomal dominant or an autosomal recessive manner. (nih.gov)
  • The parents of an individual with autosomal recessive NS are typically heterozygotes (i.e., have one LZTR1 pathogenic variant), and may either be asymptomatic or have mild features of NS. (nih.gov)
  • Family history of similarly affected children could suggest a familial form of hypogonadism or other hormone deficiency, defect in steroidogenesis (autosomal recessive), or androgen insensitivity (X-linked). (medscape.com)
  • The inheritance pattern is autosomal dominant ( FGFR1/KAL-2 gene, among others), autosomal recessive, or X-linked recessive ( KAL-1 gene). (medscape.com)
  • ZAP-70 deficiency is a rare autosomal recessive form of severe combined immunodeficiency (SCID) caused by mutations in the gene coding for T cell receptor z-chain associated protein kinase [ Chan et al. (lu.se)
  • No similar findings are present in the parents and the condition is most likely transmitted as an autosomal recessive. (arizona.edu)
  • MPS VI is a lysosomal storage disease inherited in an autosomal recessive pattern. (arizona.edu)
  • 3 Additional rare autosomal dominant or recessive disorders, such as Smith-Lemli-Opitz syndrome, Timothy syndrome and CHARGE syndrome have been described as associated with autism in clinical reports. (bmj.com)
Mutations17
  • Recent studies also show that mutations in Sos1 can cause Noonan syndrome and hereditary gingival fibromatosis type 1. (wikipedia.org)
  • Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes. (wikipedia.org)
  • Noonan and Noonan-like syndromes are multisystem genetic disorders, mainly with autosomal dominant trasmission, caused by mutations in several genes. (biomedcentral.com)
  • Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. (nih.gov)
  • Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. (nih.gov)
  • 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)
  • Approximately 50% of patients have gene mutations in PTPN11 , with SOS1 and RAF1 mutations identified in another 13% and 5-17% of patients, respectively. (medscape.com)
  • like Noonan syndrome, all of these cancers are associated with RAS signaling pathway mutations. (medscape.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)
  • NS is caused by mutations in PTPN11 (12q24.13) seen in 50% of cases, SOS1 (2p22.1) in 15%, RAF1 (3p25.2), RIT1 (1q22) and LZTR1 (22q11.21), and less commonly in other genes associated with the RAS/MAPK signaling pathway. (orpha.net)
  • Costello syndrome generally results from spontaneous mutations in a gene called HRAS . (forgottendiseases.org)
  • Because the mutations occur spontaneously, parents are unlikely (though not completely impossible) to have a second child with this syndrome. (forgottendiseases.org)
  • Noonan syndrome (NS) is caused by mutations in PTPN11 , a gene encoding the nonreceptor protein tyrosine phosphatase SHP2. (lu.se)
  • 2001]. Another forms of Noonan syndrome are caused by mutations in the KRAS [Schubbert et al. (lu.se)
  • 1999 ]. Germline mutations in PTPN11 lead to Noonan syndrome associated with JMML, and somatic PTPN11 mutations are associated with isolated JMML [Tartaglia et al. (lu.se)
  • A number of genetic mutations can result in Noonan syndrome. (handwiki.org)
  • Background Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). (bmj.com)
RAF11
  • SHP2 (encoded by PTPN11), SOS1, BRAF, RAF1 and MEK1 positively contribute to RAS-MAPK signaling through complex autoinhibitory mechanisms, that fail when these genes have mutated. (biomedcentral.com)
Features of Noonan syndrome include1
  • 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. (handwiki.org)
Congenital6
  • 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)
  • BACKGROUND: Congenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. (bvsalud.org)
  • Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. (nih.gov)
  • Other congenital anomalies may provide clues to a genetic syndrome. (medscape.com)
  • 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. (handwiki.org)
Mutation2
  • [1] The condition may be inherited as an autosomal dominant condition or occur as a new mutation. (handwiki.org)
  • The most well established of these, including fragile X syndrome, tuberous sclerosis, Rett syndrome, and PTEN mutation account for up to 5% of ASDs. (bmj.com)
Gene4
  • Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene. (wikipedia.org)
  • 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)
Genes8
  • Although the tumor risk in patients with related SOS1 NS was previously considered lower than in other forms linked to other genes, over the years a significant incidence of some solid tumors has been reported in these patients including embryonal rhabdomyosarcoma, Sertoli cell testis tumor, granular cell tumors of the skin and mandibular multiple giant cell lesions (MGCLs). (biomedcentral.com)
  • The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. (nih.gov)
  • A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. (nih.gov)
  • We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. (nih.gov)
  • 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)
  • Several additional genes associated with a Noonan syndrome-like phenotype have been identified. (bvsalud.org)
  • The clinical spectrum of NS may differ slightly between causative genes, and some forms have been described as ''Noonan like'' (NS-like disorder with juvenile myelomonocytic leukemia and NS-like disorder with loose anagen hair). (orpha.net)
  • Proporciona un análisis completo de los genes involucrados en esta enfermedad utilizando secuenciación de próxima generación (NGS) para comprender completamente el espectro de genes relevantes involucrados. (igenomix.com)
Multisystemic disorder1
  • Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. (nih.gov)
Clinical5
  • These patients were previously thought to have a form of Turner syndrome , with which Noonan syndrome shares numerous clinical features. (medscape.com)
  • OMIM 163950) is an autosomal dominant RASopathy with variable clinical expression and genetic heterogeneity. (bvsalud.org)
  • Clinical presentation and variants in patients with Noonan syndrome are this study's objectives. (bvsalud.org)
  • CONCLUSION: The identification of the genetic substrate in our patient confirmed the clinical diagnosis of Wolfram syndrome and allowed us to provide him an appropriate management and genetic counseling to his family. (bvsalud.org)
  • A diagnosis of Costello syndrome is suspected based on clinical findings, including those listed on this page. (forgottendiseases.org)
Diagnosis2
  • The diagnosis of Wolfram syndrome was made based on insulin-dependent diabetes, optic nerve atrophy, sensorineural deafness, urological abnormalities and psychiatric illness. (bvsalud.org)
  • The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. (handwiki.org)
Mental retardation1
LZTR12
  • While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. (nih.gov)
  • Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome. (nih.gov)
Disorder3
Rasopathies2
RASopathy1
  • [3] [1] Noonan syndrome is a type of RASopathy , the underlying mechanism for which involves attenuation of the RAS/MAPK cell signaling pathway. (handwiki.org)
Lymphedema2
  • 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. (handwiki.org)
  • It is believed that developmental defects and the resulting dysfunction of the lymphatic system are the cause of primary lymphedema, as well as associated syndromes, and can be genetically determined [ 5 ]. (biomedcentral.com)
19631
  • [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)
Myelodysplastic2
  • JMML is a myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukaemia [ Hasle et al. (lu.se)
  • Myelodysplastic syndromes (MDS) are uncommon in children and have a poor prognosis. (nature.com)
Symptoms2
  • 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)
  • If you suspect that your child has Costello syndrome, check with your family physician, who will compare your child's signs and symptoms with those known to occur in Costello syndrome. (forgottendiseases.org)
Webbed neck1
Malignancies1
  • Hematologic malignancies occurred most frequently, while 2 malignancies not previously observed in Noonan syndrome were found: a malignant mastocytosis and malignant epithelioid angiosarcoma. (medscape.com)
Characteristics1
  • The facial characteristics are most prominent in infancy, becoming less apparent with age in many people with Noonan syndrome. (handwiki.org)
Abnormal3
  • An abnormal sense of smell (anosmia or hyposmia) suggests Kallmann syndrome (hypogonadotropic hypogonadism with abnormal olfaction). (medscape.com)
  • 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)
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)
Disease1
  • Many autosomal dominant disorders are inherited from a parent who has the disease. (forgottendiseases.org)
Cancers1
  • Noonan syndrome is also characterized by a slight increase in the risk for certain cancers. (medscape.com)
Occur2
Variant3
  • This second variant has never been described in patients with Wolfram syndrome. (bvsalud.org)
  • While many individuals with autosomal dominant NS have a de nov o pathogenic variant, an affected parent is recognized in 30%-75% of families. (nih.gov)
  • Each child of an individual with autosomal dominant NS has a 50% chance of inheriting the pathogenic variant. (nih.gov)
Patients3
Form1
  • As an example, people with Costello syndrome have an increased risk for a type of cancer called rhabodmyosarcoma, which tends to form in muscles that attach to bones (1, 2). (forgottendiseases.org)
Forms1
  • Other forms of cancer associated with Costello syndrome include neuroblastoma, which is a cancer that develops in nerve tissue formed very early in development (before birth). (forgottendiseases.org)