Doença genética multissistêmica rara caracterizada por lentigos, cardiomiopatia hipertrófica, baixa estatura, deformidade pectus e características faciais dismórficas.
Introdução
O que você precisa saber de cara
Doença genética multissistêmica rara caracterizada por lentigos, cardiomiopatia hipertrófica, baixa estatura, deformidade pectus e características faciais dismórficas.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 34 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 97 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
3 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant.
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and
CytoplasmCell membraneMitochondrionNucleus
Noonan syndrome 5
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179)
NucleusCytoplasmCell membrane
Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:14739280, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573, PubMed:32184441). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity
CytoplasmNucleus
LEOPARD syndrome 1
A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
Medicamentos aprovados (FDA)
2 medicamentos encontrados nos registros da FDA americana.
Variantes genéticas (ClinVar)
985 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 25 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
50 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Síndrome Noonan com lentigos múltiplos
Centros de Referência SUS
24 centros habilitados pelo SUS para Síndrome Noonan com lentigos múltiplos
Centros para Síndrome Noonan com lentigos múltiplos
Detalhes dos centros
Hospital Universitário Prof. Edgard Santos (HUPES)
R. Dr. Augusto Viana, s/n - Canela, Salvador - BA, 40110-060 · CNES 0003808
Serviço de Referência
Hospital Infantil Albert Sabin
R. Tertuliano Sales, 544 - Vila União, Fortaleza - CE, 60410-794 · CNES 2407876
Serviço de Referência
Hospital de Apoio de Brasília (HAB)
AENW 3 Lote A Setor Noroeste - Plano Piloto, Brasília - DF, 70684-831 · CNES 0010456
Serviço de Referência
Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA)
Av. Min. Salgado Filho, 918 - Soteco, Vila Velha - ES, 29106-010 · CNES 6631207
Serviço de Referência
Hospital das Clínicas da UFG
Rua 235 QD. 68 Lote Área, Nº 285, s/nº - Setor Leste Universitário, Goiânia - GO, 74605-050 · CNES 2338424
Serviço de Referência
Hospital Universitário da UFJF
R. Catulo Breviglieri, Bairro - s/n - Santa Catarina, Juiz de Fora - MG, 36036-110 · CNES 2297442
Atenção Especializada
Hospital das Clínicas da UFMG
Av. Prof. Alfredo Balena, 110 - Santa Efigênia, Belo Horizonte - MG, 30130-100 · CNES 2280167
Serviço de Referência
Hospital Universitário Julio Müller (HUJM)
R. Luis Philippe Pereira Leite, s/n - Alvorada, Cuiabá - MT, 78048-902 · CNES 2726092
Atenção Especializada
Hospital Universitário João de Barros Barreto
R. dos Mundurucus, 4487 - Guamá, Belém - PA, 66073-000 · CNES 2337878
Serviço de Referência
Hospital Universitário Lauro Wanderley (HULW)
R. Tabeliao Estanislau Eloy, 585 - Castelo Branco, João Pessoa - PB, 58050-585 · CNES 0002470
Atenção Especializada
Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
R. dos Coelhos, 300 - Boa Vista, Recife - PE, 50070-902 · CNES 0000647
Serviço de Referência
Hospital Pequeno Príncipe
R. Des. Motta, 1070 - Água Verde, Curitiba - PR, 80250-060 · CNES 3143805
Serviço de Referência
Hospital Universitário Regional de Maringá (HUM)
Av. Mandacaru, 1590 - Parque das Laranjeiras, Maringá - PR, 87083-240 · CNES 2216108
Atenção Especializada
Hospital de Clínicas da UFPR
R. Gen. Carneiro, 181 - Alto da Glória, Curitiba - PR, 80060-900 · CNES 2364980
Serviço de Referência
Hospital Universitário Pedro Ernesto (HUPE-UERJ)
Blvd. 28 de Setembro, 77 - Vila Isabel, Rio de Janeiro - RJ, 20551-030 · CNES 2280221
Serviço de Referência
Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz)
Av. Rui Barbosa, 716 - Flamengo, Rio de Janeiro - RJ, 22250-020 · CNES 2269988
Serviço de Referência
Hospital São Lucas da PUCRS
Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre - RS, 90610-000 · CNES 2232928
Serviço de Referência
Hospital de Clínicas de Porto Alegre (HCPA)
Rua Ramiro Barcelos, 2350 Bloco A - Av. Protásio Alves, 211 - Bloco B e C - Santa Cecília, Porto Alegre - RS, 90035-903 · CNES 2237601
Serviço de Referência
Hospital Universitário da UFSC (HU-UFSC)
R. Profa. Maria Flora Pausewang - Trindade, Florianópolis - SC, 88036-800 · CNES 2560356
Serviço de Referência
Hospital das Clínicas da FMUSP
R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo - SP, 05403-010 · CNES 2077485
Serviço de Referência
Hospital de Base de São José do Rio Preto
Av. Brg. Faria Lima, 5544 - Vila Sao Jose, São José do Rio Preto - SP, 15090-000 · CNES 2079798
Atenção Especializada
Hospital de Clínicas da UNICAMP
R. Vital Brasil, 251 - Cidade Universitária, Campinas - SP, 13083-888 · CNES 2748223
Serviço de Referência
Hospital de Clínicas de Ribeirão Preto (HCRP-USP)
R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto - SP, 14015-010 · CNES 2082187
Serviço de Referência
UNIFESP / Hospital São Paulo
R. Napoleão de Barros, 715 - Vila Clementino, São Paulo - SP, 04024-002 · CNES 2688689
Serviço de Referência
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Ensaios em destaque
🟢 Recrutando agora
1 pesquisa recrutando participantes. Converse com seu médico sobre a possibilidade de participar.
Outros ensaios clínicos
2 ensaios clínicos encontrados, 1 ativos.
Publicações mais relevantes
Clinical phenotypes and cochlear implant outcomes in patients with PTPN11-associated noonan spectrum disorders: Insights from a genetically screened cohort.
We characterized the clinical features of PTPN11-related deafness and evaluated the outcomes of cochlear implantation in affected patients. Whole-exome sequencing and bioinformatic analyses were performed in a cohort of 467 individuals with congenital sensorineural hearing loss to identify potential genetic etiologies. Four patients harboring PTPN11 variants were reviewed for their clinical characteristics and post-implantation auditory rehabilitation outcomes. PTPN11 variants were identified in four patients (Cases 1-4). A missense variant c.1391G > C (p.Gly464Ala) in exon 12 was detected in Case 1 and the recurrent variant c.836A > G (p.Tyr279Cys) in exon 7 was identified in Case 2. Both patients were diagnosed with Noonan syndrome with multiple lentigines. Missense variants c.1510A > G (p.Met504Val) in exon 13 and c.923A > G (p.Asn308Ser) in exon 8 were found in Cases 3 and 4, respectively; both were diagnosed with Noonan syndrome. Cases 1, 2, and 4 underwent cochlear implantation and demonstrated favorable postoperative auditory and speech outcomes. Our study provides a comprehensive characterization of auditory, speech and systemic phenotypes in PTPN11-related Noonan spectrum disorders and demonstrates that cochlear implantation is highly effective for severe-to-profound hearing loss. These findings emphasize the value of early genetic diagnosis and emphasize the importance of coordinated, interdisciplinary management.
Noonan Syndrome With Multiple Lentigines Mimicking Obstructive Hypertrophic Cardiomyopathy Treated by Septal Myectomy.
Noonan syndrome with multiple lentigines (NSML) is a rare RASopathy characterized by lentigines, craniofacial anomalies, and cardiac involvement. Hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract obstruction is a frequent phenotype and may require interventional therapy. We present a 43-year-old woman with NSML and obstructive HCM. Despite optimized pharmacologic therapy and implantable cardioverter-defibrillator implantation, she developed progressive dyspnea and palpitations. Multidisciplinary heart team evaluation favored surgical septal myectomy with papillary muscle plasty, given unfavorable anatomy for alcohol septal ablation. Postoperative echocardiography showed marked gradient reduction and symptom relief. Approximately 5% to 10% of patients with HCM remain refractory to medical therapy. In phenocopies such as NSML, therapeutic decisions should be individualized. Surgical myectomy is a safe alternative when septal anatomy precludes alcohol septal ablation. Septal reduction therapies may be considered in NSML with left ventricular outflow tract obstruction. Heart team discussion is essential. Surgical myectomy can provide sustained functional improvement.
Development and Treatment of Severe Lordoscoliosis in a Patient With Noonan Syndrome With Multiple Lentigines (NSML): A Case Report.
Noonan syndrome with multiple lentigines (NSML) is an allelic variant of Noonan syndrome (NS), which can exhibit multisystemic features, including sensorineural hearing loss (SNHL) and skeletal anomalies. We report on a patient with this rare condition who developed an uncommon syndromic feature of severe lordoscoliosis requiring surgical intervention, whose comorbidities complicated the perioperative course, including the preclusion of magnetic resonance imaging (MRI) and relative contraindication to transcranial motor evoked potentials (TcMEPs). We discuss the use of preoperative computed tomography (CT) and somatosensory evoked potentials (SSEPs) in facilitating the consent process for surgery where MRI and TcMEPs are impracticable, as well as the intraoperative measures taken to minimise complications in this case. We also highlight the importance of multispecialty, multidisciplinary involvement in the management of such patients. In this patient whose severe lordoscoliosis led to persistent back pain and airway compression, posterior spinal fusion achieved satisfactory deformity correction and excellent clinical outcome, which was maintained at follow-up.
Genotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.
RASopathies are a heterogeneous group of conditions of the RAS/mitogen-activated protein kinase pathway presenting with overlapping features such as growth deficiency, neurodevelopmental disorders, cardiac defects, craniofacial dysmorphisms, cutaneous and ocular abnormalities, and increased cancer risk. This retrospective study analyzed the medical records regarding clinical and molecular data from 2018 to 2024 in a single center for rare diseases of individuals diagnosed with Noonan syndrome and related disorders previously submitted to diagnostic molecular analysis through next-generation sequencing techniques. Twenty-four patients were enrolled with an even sex ratio distribution and ages ranging from 1 month to 16 years at first evaluation. The main reason for referral was diagnostic assessment due to a combination of dysmorphic features (24/24; 100%), growth deficiency (18/24; 75%), neurodevelopmental disorders (15/24; 62.5%), and/or heart disease (13/24; 54.1%). Final diagnoses included 15 individuals with Noonan syndrome (nine with variants in PTPN11, two in SOS1, and one each in LZTR1, A2ML1, and MRAS, besides one with variants in both LZTR1 and SOS1), two with Noonan syndrome with multiple lentigines (both with variants in PTPN11), two with Neurofibromatosis-Noonan (NF1), two with cardiofaciocutaneous syndrome (BRAF), and one each with Noonan syndrome-like with loose anagen hair (PPP1CB), Noonan syndrome-like (CBL), and Costello syndrome (HRAS); one individual presented with a double diagnosis of Noonan and Klinefelter syndromes. Three pairs of unrelated patients presented recurrent variants in the PTPN11 gene, partially concordant in phenotypic correlation among the pairs but not fully concordant compared to previously described cases in the literature. Undescribed features in this group included myopathy and megacolon in a patient with Noonan syndrome-like, hypogonadotropic hypogonadism, and azoospermia in a patient with Noonan syndrome-like with loose anagen hair, and schizophrenia in a patient with Costello syndrome. One patient with Noonan syndrome had a novel variant of the A2ML1 gene (c.1829G>A), but the variant was strictly of uncertain significance, while c.2033G>A in the LZTR1 gene and c.1A>G in the NF1 gene are variants for the first time associated with features of Noonan syndrome.
Dysregulated TGFβ-ERK Signaling Drives Aberrant Extracellular Matrix Production in Noonan Syndrome-Associated Pulmonary Valve Stenosis.
Pulmonary valve stenosis (PVS) is the most common congenital heart defect in Noonan syndrome (NS) and related RASopathies, yet the molecular mechanisms linking pathogenic variants to the valve pathology remain poorly defined. Here, we utilized a human iPSC-based valve differentiation platform to generate the cardiac valve cell lineages-including fibrosa and spongiosa valve interstitial cell (VIC) subtypes. CRISPR-edited iPSCs harboring NS gain-of-function RAS/MAPK and Noonan syndrome with multiple lentigines (NSML) dominant-negative RAS/MAPK variants exhibited early defects in mesodermal and endocardial specification in all genotypes. Additionally, NS-iPSC endocardial cells exhibited defects in endothelial-to-mesenchymal transition (EndMT) specifically towards fibrosa VICs, which was most pronounced in PTPN11 N308D (N308D) cells. Single-cell transcriptomics revealed widespread dysregulation of extracellular matrix (ECM) programs in N308D fibrosa VICs, including increased expression of collagens and proteoglycans, as well as dysregulation of multiple genes involved in ECM remodeling. We also detected activation of RAS-MAPK, TGFβ, and fibrosis-associated pathways in our transcriptional dataset. Mass spectrometry-based phosphoproteomics confirmed coordinated increases in ERK, PKC, and stress-related kinases, as well as enhanced activity of the TGFβ receptor. Functionally, N308D fibrosa VICs exhibited exaggerated upregulation of ECM genes in the presence of TGFβ2 ligand, suggesting that these cells are hypersensitive to TGFβ stimulation. Furthermore, we demonstrated that this pathological ECM-program occurs independently of BAMBI, a negative regulator of TGFβ signaling that was found to be decreased in N308D fibrosa VICs. Lastly, we performed histopathological analyses of stenotic pulmonary valves from two NS infants, which demonstrated marked overproduction and disorganization of ECM, mirroring the findings from our iPSC-based disease model. Together, our data reveal a central mechanism where NS-associated alleles sensitize fibrosa VICs to TGFβ, which leads to aberrant downstream signaling and drives the pathological ECM program in NS-associated PVS.
Publicações recentes
Cancer risk in adults with pathogenic germline variants in RAS/MAPK genes using genomic ascertainment.
Clinical phenotypes and cochlear implant outcomes in patients with PTPN11-associated noonan spectrum disorders: Insights from a genetically screened cohort.
Noonan Syndrome With Multiple Lentigines Mimicking Obstructive Hypertrophic Cardiomyopathy Treated by Septal Myectomy.
Development and Treatment of Severe Lordoscoliosis in a Patient With Noonan Syndrome With Multiple Lentigines (NSML): A Case Report.
Genotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.
📚 EuropePMC44 artigos no totalmostrando 109
Clinical phenotypes and cochlear implant outcomes in patients with PTPN11-associated noonan spectrum disorders: Insights from a genetically screened cohort.
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck SurgeryNoonan Syndrome With Multiple Lentigines Mimicking Obstructive Hypertrophic Cardiomyopathy Treated by Septal Myectomy.
JACC. Case reportsDevelopment and Treatment of Severe Lordoscoliosis in a Patient With Noonan Syndrome With Multiple Lentigines (NSML): A Case Report.
CureusGenotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.
Molecular syndromologyDysregulated TGFβ-ERK Signaling Drives Aberrant Extracellular Matrix Production in Noonan Syndrome-Associated Pulmonary Valve Stenosis.
bioRxiv : the preprint server for biologyNeuropathic Pain and Enlarged Nerves in Adult Noonan Syndrome and Noonan Syndrome With Multiple Lentigines: Health-Related Quality of Life and Neurologic Symptoms.
American journal of medical genetics. Part AMolecular and Clinical Profiles of Patients with RASopathies: Targeted Next-Generation Sequencing Panel Results and Identification of 14 Novel Disease-Causing Variants.
Molecular syndromologyGenotype-phenotype correlations with autism spectrum disorder-related traits in noonan syndrome and noonan syndrome with multiple lentigines: a cross-sectional study.
Molecular autismExecutive and Social Functioning in Children and Adolescents With Noonan Syndromes: Cognition and Behavior.
JAACAP openSHP2 genetic variants in NSML-associated RASopathies disrupt the PZR-IRX transcription factor signaling axis.
Proceedings of the National Academy of Sciences of the United States of AmericaEverolimus therapy in an infant with Noonan syndrome with multiple lentigines.
Annals of pediatric cardiology[Hypertrophy of the lumbosacral nerve roots in Noonan syndrome with multiple lentigines: a case report].
Rinsho shinkeigaku = Clinical neurologyRASopathies. Part II: Cutaneous and extracutaneous manifestations.
Journal of the American Academy of DermatologyRASopathies. Part I: Genetics and therapeutic considerations.
Journal of the American Academy of DermatologyRapamycin treatment for progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines.
Kardiologia polska[Perioperative management of cochlear implantation and analysis on the influencing factors of efficacy in patients diagnosed as hereditary syndromic hearing loss].
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgeryCase Report: A rare case of Noonan syndrome with multiple lentigines manifesting as cardiac enlargement.
Frontiers in cardiovascular medicineGenomic ascertainment to quantify prevalence and cancer risk in adults with pathogenic and likely pathogenic germline variants in RASopathy genes.
medRxiv : the preprint server for health sciencesOrbital and Lumbosacral Plexiform Neurofibroma with PTPN11 Mutation: A Form of the RASopathy.
CureusAtypical left-ventricular hypertrophy with apical aneurysm in leopard syndrome.
The international journal of cardiovascular imagingSHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.
Nature communicationsPaternally Inherited Noonan Syndrome Caused by a PTPN11 Variant May Exhibit Mild Symptoms: A Case Report and Literature Review.
GenesA novel variant in PTPN11, c.1277A>G p.(His426Arg), in a patient with Noonan syndrome with multiple lentigines.
Clinical and experimental dermatologyMEK Inhibition for RASopathy-Associated Hypertrophic Cardiomyopathy: Clinical Application of a Basic Concept.
The Canadian journal of cardiologyCoexisting PTPN11 and TNNT2 mutations in noonan syndrome with multiple lentigines.
QJM : monthly journal of the Association of Physicians[Translated article] Noonan Syndrome With Multiple Lentigines.
Actas dermo-sifiliograficasCase report: Distinctive cardiac features and phenotypic characteristics of Noonan syndrome with multiple lentigines among three generations in one family.
Frontiers in cardiovascular medicineHypertrophic cardiomyopathy in an adult patient with Noonan syndrome with multiple lentigines.
Clinical case reportsLessons From a Genotype-Phenotype Study About the Clinical Spectrum of Hypertrophic Cardiomyopathy Associated With Noonan Syndrome With Multiple Lentigines and PTPN11-Mutations.
Circulation. Genomic and precision medicineA rare mutation in a patient with Noonan syndrome with multiple lentigines.
JAAD case reportsNatural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines.
Circulation. Genomic and precision medicineDermatological manifestations, management, and care in RASopathies.
American journal of medical genetics. Part C, Seminars in medical geneticsNew prospectives on treatment opportunities in RASopathies.
American journal of medical genetics. Part C, Seminars in medical geneticsClinical overview on RASopathies.
American journal of medical genetics. Part C, Seminars in medical geneticsThe heart in RASopathies.
American journal of medical genetics. Part C, Seminars in medical geneticsModeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.
Frontiers in cell and developmental biologyEffects of Noonan Syndrome-Germline Mutations on Mitochondria and Energy Metabolism.
CellsCognitive Phenotype and Psychopathology in Noonan Syndrome Spectrum Disorders through Various Ras/MAPK Pathway Associated Gene Variants.
Journal of clinical medicineEpilepsy in a cohort of children with Noonan syndrome and related disorders.
European journal of pediatricsTargeting SHP2 phosphatase in hematological malignancies.
Expert opinion on therapeutic targetsCochlear Implantation in Noonan Syndrome With and Without Multiple Lentigines: A Case Report and Systematic Review.
Otology & neurotology openAn Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathies.
Cardiovascular drugs and therapyRASopathies: Dermatologists' viewpoints.
Indian journal of dermatology, venereology and leprologyThe RASopathies: Biology, genetics and therapeutic options.
Advances in cancer researchNatural history of left ventricular hypertrophy in infants of diabetic mothers.
International journal of cardiologyDiscriminating between competing models for the allosteric regulation of oncogenic phosphatase SHP2 by characterizing its active state.
Computational and structural biotechnology journalDermatologic manifestations of pediatric cardiovascular diseases: Skin as a reflection of the heart.
Pediatric dermatologyOPTIC DISK COLOBOMA AND CONTRALATERAL OPTIC DISK PIT MACULOPATHY TREATED BY VITRECTOMY IN A PATIENT WITH NOONAN SYNDROME WITH MULTIPLE LENTIGINES.
Retinal cases & brief reportsNoonan Syndrome with Multiple Lentigines and PTPN11 Mutation: A Case with Intracerebral Hemorrhage.
Molecular syndromologyLow-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines.
Cardiovascular drugs and therapyNoonan Syndrome With Multiple Lentigines: Subtle Key Skin Clues to the Diagnosis.
Actas dermo-sifiliograficasCompound heterozygosity for PTPN11 variants in a subject with Noonan syndrome provides insights into the mechanism of SHP2-related disorders.
Clinical geneticsGenotype-phenotype association by echocardiography offers incremental value in patients with Noonan Syndrome with Multiple Lentigines.
Pediatric researchPhase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation.
CellTargeting a Pathogenic Cysteine Mutation: Discovery of a Specific Inhibitor of Y279C SHP2.
BiochemistryCongenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms.
Journal of medical geneticsTyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines.
JCI insightMelanoma in Noonan Syndrome With Multiple Lentigines (Leopard Syndrome): A New Case.
Actas dermo-sifiliograficasGermline and sporadic cancers driven by the RAS pathway: parallels and contrasts.
Annals of oncology : official journal of the European Society for Medical OncologyLegius Syndrome and its Relationship with Neurofibromatosis Type 1.
Acta dermato-venereologicaExpanding the Noonan spectrum/RASopathy NGS panel: Benefits of adding NF1 and SPRED1.
Molecular genetics & genomic medicineCafé au Lait Macules and Associated Genetic Syndromes.
Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & PractitionersClinical and molecular characterization of children with Noonan syndrome and other RASopathies in Argentina.
Archivos argentinos de pediatria[Case report and diagnosis of Noonan syndrome with multiple lentigines with deafness as its main clinical feature].
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgeryPediatric patients with RASopathy-associated hypertrophic cardiomyopathy: the multifaceted consequences of PTPN11 mutations.
Orphanet journal of rare diseasesInvestigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation.
Journal of biomolecular structure & dynamicsNoonan syndrome with multiple lentigines and prominent keratosis pilaris.
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDGOut-of-hospital cardiac arrest and survival in a patient with Noonan syndrome and multiple lentigines: a case report.
Journal of medical case reportsRAF1 variant in a patient with Noonan syndrome with multiple lentigines and craniosynostosis.
American journal of medical genetics. Part APathogenesis of Growth Failure in Rasopathies.
Pediatric endocrinology reviews : PERClinical Manifestations of Noonan Syndrome and Related Disorders.
Pediatric endocrinology reviews : PERFirst International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics.
American journal of medical genetics. Part AGenetic landscape of RASopathies in Chinese: Three decades' experience in Hong Kong.
American journal of medical genetics. Part C, Seminars in medical geneticsGeneration of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene.
Stem cell researchWidespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines.
International journal of dermatologyNonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients.
American journal of medical genetics. Part AThe RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway.
Endocrine reviewsRAS signalling in energy metabolism and rare human diseases.
Biochimica et biophysica acta. BioenergeticsGain-of-function mutations in the gene encoding the tyrosine phosphatase SHP2 induce hydrocephalus in a catalytically dependent manner.
Science signalingPatient with confirmed LEOPARD syndrome developing multiple melanoma.
Dermatology practical & conceptualNeurocutaneous Disorders.
Continuum (Minneapolis, Minn.)Noonan syndrome with multiple lentigines and associated craniosynostosis.
Clinical and experimental dermatologyTargeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders.
BMC medical genomicsHeterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines.
Journal of molecular and cellular cardiologyNoonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor.
The Journal of dermatologyCraniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype.
American journal of medical genetics. Part AA review of craniofacial and dental findings of the RASopathies.
Orthodontics & craniofacial researchIn vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy.
PloS oneCochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11.
International journal of pediatric otorhinolaryngologyMultiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.
Clinical geneticsModeling RASopathies with Genetically Modified Mouse Models.
Methods in molecular biology (Clifton, N.J.)Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review).
Molecular medicine reportsChoroidal abnormalities in café-au-lait syndromes: a new differential diagnostic tool?
Clinical geneticsCardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies.
Pediatric cardiologyRASopathies: Presentation at the Genome, Interactome, and Phenome Levels.
Molecular syndromologyDevelopmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines.
The Journal of clinical investigationCell type-specific roles of RAS-MAPK signaling in learning and memory: Implications in neurodevelopmental disorders.
Neurobiology of learning and memoryMultiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines.
European journal of medical geneticsThe Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway.
American journal of medical genetics. Part AHypertrophic neuropathy in Noonan syndrome with multiple lentigines.
American journal of medical genetics. Part ARecent advances in RASopathies.
Journal of human geneticsCardiomyopathies in Noonan syndrome and the other RASopathies.
Progress in pediatric cardiologyOccurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.
American journal of medical genetics. Part ASHP2 sails from physiology to pathology.
European journal of medical geneticsParaspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines.
Journal of medical geneticsCopy number variants including RAS pathway genes-How much RASopathy is in the phenotype?
American journal of medical genetics. Part AElevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines.
American journal of physiology. Heart and circulatory physiologyRapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: palliative treatment with a rapamycin analog.
American journal of medical genetics. Part AMalignancy in Noonan syndrome and related disorders.
Clinical geneticsAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
Ainda não temos associações cadastradas para Síndrome Noonan com lentigos múltiplos.
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Comunidades
Grupos ativos de quem convive com esta doença aqui no Raras
Ainda não existe comunidade no Raras para Síndrome Noonan com lentigos múltiplos
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Clinical phenotypes and cochlear implant outcomes in patients with PTPN11-associated noonan spectrum disorders: Insights from a genetically screened cohort.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery· 2026· PMID 41786942mais citado
- Noonan Syndrome With Multiple Lentigines Mimicking Obstructive Hypertrophic Cardiomyopathy Treated by Septal Myectomy.
- Development and Treatment of Severe Lordoscoliosis in a Patient With Noonan Syndrome With Multiple Lentigines (NSML): A Case Report.
- Genotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.
- Dysregulated TGFβ-ERK Signaling Drives Aberrant Extracellular Matrix Production in Noonan Syndrome-Associated Pulmonary Valve Stenosis.
- Cancer risk in adults with pathogenic germline variants in RAS/MAPK genes using genomic ascertainment.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:500(Orphanet)
- MONDO:0007893(MONDO)
- GARD:1100(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q1798016(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
