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1.
Clin Dermatol ; 38(4): 455-461, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972603

RESUMO

RASopathies are a group of disorders characterized by mutations in the RAS-MAPK pathway. RAS-MAP signaling plays a critical role in cell differentiation, proliferation, and survival. Germline mutations can result in distinctive syndromes, including Noonan syndrome, Costello syndrome, and neurofibromatosis type 1. Mosaic RASopathies can present as localized cutaneous lesions like epidermal nevi and nevus sebaceous, or more extensive conditions such as encephalocraniocutaneous lipomatosis. We review the heterogenous presentation of RAS mutations, discuss new targeted therapies, and highlight areas of uncertainty, including carcinogenesis risk and appropriate screening.


Assuntos
Síndrome de Costello/genética , Oftalmopatias/genética , Mutação em Linhagem Germinativa , Lipomatose/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas Monoméricas de Ligação ao GTP/genética , Síndromes Neurocutâneas/genética , Neurofibromatose 1/genética , Síndrome de Noonan/genética , Síndrome de Costello/diagnóstico , Síndrome de Costello/terapia , Oftalmopatias/diagnóstico por imagem , Oftalmopatias/terapia , Humanos , Lipomatose/diagnóstico por imagem , Lipomatose/terapia , Terapia de Alvo Molecular , Mutação , Síndromes Neurocutâneas/diagnóstico por imagem , Síndromes Neurocutâneas/terapia , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/terapia , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/terapia , Risco
2.
Medwave ; 20(2): e7826, 2020 Feb 26.
Artigo em Espanhol | MEDLINE | ID: mdl-32119651

RESUMO

Noonan syndrome is an autosomal dominant inherited disorder with variable phenotypic expression. It belongs to the group of diseases known as RASopathies, which are characterized by mutations in the RAS genes. Patients develop symptoms such as facial dysmorphism, short stature, congenital heart disease, musculoskeletal disorders and mental retardation. In this article, we report a case of Noonan syndrome in a 14-year-old patient, diagnosed in a primary health center in Ecuador. The syndrome was identified through clinical diagnosis, after which the patient was referred to the secondary and tertiary levels for specialized care.


Assuntos
Síndrome de Noonan/diagnóstico , Atenção Primária à Saúde , Adolescente , Equador , Humanos , Mutação , Síndrome de Noonan/genética , Síndrome de Noonan/terapia , Proteínas ras/genética
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(3): 324-328, 2020 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-32128752

RESUMO

Noonan syndrome is a common genetic disease characterized by peculiar face, short stature, congenital heart disease and thoracic deformity. The pathogenesis of Noonan syndrome is mainly related to abnormal Ras-MAPK signal pathway which involves more than 16 genes including (PTPN11, SOS1, RAF1)] and KRAS. At present, there is a lack of experience in the diagnosis and treatment of Noonan syndrome in China. This guideline has summarized the clinical manifestation, pathogenesis, diagnostic criteria and treatment for Noonan syndrome, with an aim to improve the diagnostic level and clinical management of patients with this syndrome.


Assuntos
Síndrome de Noonan/diagnóstico , Síndrome de Noonan/terapia , Guias de Prática Clínica como Assunto , China , Nanismo , Humanos , Mutação , Transdução de Sinais
6.
BMC Cardiovasc Disord ; 18(1): 148, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012103

RESUMO

BACKGROUND: In patients with Noonan syndrome (NS), cardiac disorders such as pulmonary valve stenosis (PS) or hypertrophic cardiomyopathy (HCM) are common. While some patients can develop heart failure associated with HCM, the long-term outcome of adult patients with NS is reported to be good. Fatal outcomes of heart failure in patients with NS but without HCM are rare. CASE PRESENTATION: We report a 25-year-old Japanese woman diagnosed with NS in adulthood. She exhibited short stature and minor facial dysmorphism and was diagnosed with PS at 1 year of age. After surgical valvuloplasty for PS at 6 years of age, her general condition became stable without specific medical treatment. She discontinued regular medical follow-up for PS. At 21 years of age, she developed acute decompensated heart failure, which was mainly right-sided heart failure due to severe pulmonary regurgitation (PR) and tricuspid regurgitation (TR). There was no evidence of HCM or PS recurrence. On the basis of the history of PS and characteristic physical features including short stature, webbed neck, and hypertelorism, she was clinically diagnosed with NS. At 25 years of age, she developed heart failure of both sides due to PR, TR and late-onset severe mitral stenosis (MS). The etiology of MS was uncertain. Owing to the patient's condition, surgical options were considered to be extremely high risk. She was treated with optimal medical treatment as well as the occasional abdominal cavity drainage for recurrent ascites; however, she died of decompensated heart failure at 27 years of age. CONCLUSIONS: We describe an adult patient with NS without HCM who died of heart failure caused by severe PR, TR and MS. Clinicians should recognize that ongoing or late-onset cardiac disorders can develop in patients with NS, and lead to fatal heart failure. Optimal medical follow-up to monitor cardiac function and early identification of heart failure are important.


Assuntos
Insuficiência Cardíaca/etiologia , Estenose da Valva Mitral/etiologia , Síndrome de Noonan/complicações , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Tricúspide/etiologia , Adulto , Ecocardiografia Doppler em Cores , Evolução Fatal , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/terapia , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/terapia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/fisiopatologia , Insuficiência da Valva Pulmonar/terapia , Índice de Gravidade de Doença , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/terapia
7.
Curr Opin Endocrinol Diabetes Obes ; 25(1): 67-73, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29120925

RESUMO

PURPOSE OF REVIEW: To provide an update on recent developments on Noonan syndrome with a special focus on endocrinology, bone, and metabolism aspects. The key issues still to be resolved and the future therapeutic perspectives will be discussed. RECENT FINDINGS: The discovery of the molecular genetic causes of Noonan syndrome and Noonan-syndrome-related disorders has permitted us to better understand the mechanisms underlying the different symptoms of these diseases and to establish genotype-phenotype correlations (in growth patterns for example). In addition to the classical clinical hallmarks of Noonan syndrome, new important aspects include decreased fertility in men, lean phenotype with increased energy expenditure and possible impact on carbohydrate metabolism/insulin sensitivity, and impaired bone health. Further clinical studies are needed to investigate the long-term impact of these findings and their possible interconnections. Finally, the understanding of the crucial role of RAS/mitogen-activated protein kinases dysregulation in the pathophysiology of Noonan syndrome allows us to devise new therapeutic approaches. Some agents are currently undergoing clinical trials in Noonan syndrome patients. SUMMARY: On the last 10 years, our knowledge of the molecular basis and the pathophysiology of Noonan syndrome has greatly advanced allowing us to gain insight in all the aspects of this disease and to devise new specific therapeutic strategies.


Assuntos
Crescimento e Desenvolvimento , Síndrome de Noonan/fisiopatologia , Estudos de Associação Genética , Crescimento e Desenvolvimento/genética , Humanos , Masculino , Mutação , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Síndrome de Noonan/terapia , Fenótipo
8.
Buenos Aires; s.n; 2018. 50 p. graf..
Não convencional em Espanhol | LILACS | ID: biblio-1009917

RESUMO

Ateneo de los residentes de Psicopedagogía del Hospital de Niños Dr Ricardo Gutiérrez, de la Ciudad de Buenos Aires, donde a partir de la práctica psicopedagógica con niños y adolescentes con patología orgánica se desarrollan cuatro ejes temáticos para describir algunas de las patologías o condiciones con las cuales se han ido encontrando en su labor cotidiana. Se relatan algunas viñetas clínicas que surgen de la experiencia en el Consultorio Interdisciplinario de Espina Bífida, con el fin de reflejar la intervención y los aportes de la psicopedagogía en ese campo. Se presenta el caso de una paciente que presentó un cuadro de Encefalitis Autoinmune por anticuerpos contra el receptor NMDAR, patología que despertó un gran interés al interior del equipo y que debido a su creciente recurrencia en los últimos tiempos, convoca a ampliar el conocimiento en ese campo, que aún se encuentra poco investigado. A continuación, se caracterizan dos patologías genéticas a través de casos de Agustín y Matías, considerando la importante incidencia de diversas condiciones genéticas en la población con la cual trabajamos. A partir de los casos clínicos seleccionados, no solo perseguimos el fin de describir y caracterizar algunos cuadros específicos, sino que a través de los mismos buscaremos plasmar los pilares fundamentales sobre los cuales asentamos nuestra mirada e intervención frente a pacientes que exigen un abordaje complejo, integral e interdisciplinario.


Assuntos
Anormalidades Congênitas/psicologia , Anormalidades Congênitas/reabilitação , Anormalidades Congênitas/terapia , Disrafismo Espinal/terapia , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Disostose Mandibulofacial/terapia , Síndrome de Noonan/terapia , Instituições de Assistência Ambulatorial , Internato não Médico
9.
Int J Mol Sci ; 18(6)2017 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-28629126

RESUMO

Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine. For DTC, surgery and radioiodine therapy followed by levothyroxine substitution remain the established therapeutic procedures. Even metastasized tumors can be cured this way. However, in rare cases of radioiodine-refractory tumors, additional options are to be discussed. These include strict suppression of thyroid-stimulating hormone (also known as thyrotropin, TSH) and external local radiotherapy. Systemic cytostatic chemotherapy does not play a significant role. Recently, multikinase or tyrosine kinase inhibitors have been approved for the treatment of radioiodine-refractory DTC. Although a benefit for overall survival has not been shown yet, these new drugs can slow down tumor progression. However, they are frequently associated with severe side effects and should be reserved for patients with threatening symptoms only.


Assuntos
Adenocarcinoma/terapia , Tratamento Farmacológico/normas , Radioterapia/normas , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma/classificação , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma Folicular/terapia , Carcinoma Papilar/terapia , Inibidores Enzimáticos/uso terapêutico , Humanos , Radioisótopos do Iodo/normas , Radioisótopos do Iodo/uso terapêutico , Metástase Neoplásica , Síndrome de Noonan/terapia , Prognóstico , Proteínas Tirosina Quinases/efeitos dos fármacos , Proteínas Tirosina Quinases/efeitos da radiação , Radioterapia Adjuvante , Câncer Papilífero da Tireoide , Hormônios Tireóideos , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico , Tireotropina/uso terapêutico , Tiroxina/uso terapêutico
10.
Int J Pediatr Otorhinolaryngol ; 97: 228-234, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28483241

RESUMO

Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. The age at which the CI surgery occurred ranged from 1 to 13 years old, and the audiological results in all five patients improved after the CI. Otological and audiological examinations in NS and NSML are important, and for those with severe hearing loss, the CI surgery improved the audiological outcome regardless of age.


Assuntos
Implante Coclear/métodos , Perda Auditiva/cirurgia , Síndrome LEOPARD/terapia , Síndrome de Noonan/terapia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Adolescente , Audiometria , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Síndrome LEOPARD/genética , Masculino , Mutação , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Estudos Retrospectivos
11.
Z Gastroenterol ; 55(2): 145-148, 2017 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-28192847

RESUMO

We present a case of a 26-year-old female patient with bloating, postprandial nausea and recurrent vomiting after solid food intake. A gastric emptying scintigraphy showed a delayed gastric emptying, defining gastroparesis. Because of her past medical history of short stature and pulmonary stenosis, we initiated genetic counseling where the diagnosis of Noonan syndrome was made. Dietary therapy and medication with domperidone quickly led to relief of the discomfort due to gastroparesis. However, prokinetics are not indicated for long-term therapy, as cardiac arrhythmia may occur. A risk-benefit assessment should be done. There are several novel approaches which need to be further investigated.


Assuntos
Dietoterapia , Domperidona/uso terapêutico , Gastroparesia/diagnóstico , Gastroparesia/terapia , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/terapia , Adulto , Antieméticos/uso terapêutico , Terapia Combinada , Diagnóstico Diferencial , Feminino , Humanos , Resultado do Tratamento
12.
Neonatal Netw ; 34(2): 117-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26803093

RESUMO

Noonan syndrome is a genetic disorder that has several features common to other conditions, making diagnosis a challenge. This column summarizes the case of a neonate with an atypical presentation of Noonan syndrome involving a fatal type of lymphangiectasia resulting in persistent pleural effusions. Radiographic features of this condition are presented along with the complexities of diagnosis and treatment.


Assuntos
Pneumopatias/congênito , Linfangiectasia/congênito , Síndrome de Noonan , Derrame Pleural/diagnóstico por imagem , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido , Diagnóstico Diferencial , Evolução Fatal , Humanos , Recém-Nascido , Pneumopatias/complicações , Pneumopatias/diagnóstico , Pneumopatias/fisiopatologia , Linfangiectasia/complicações , Linfangiectasia/diagnóstico , Linfangiectasia/fisiopatologia , Linfografia/métodos , Masculino , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/fisiopatologia , Síndrome de Noonan/terapia , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Toracentese/métodos
13.
Am Fam Physician ; 89(1): 37-43, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24444506

RESUMO

Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available.


Assuntos
Síndrome de Noonan/diagnóstico , Síndrome de Noonan/terapia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Síndrome de Noonan/epidemiologia , Síndrome de Noonan/genética , Adulto Jovem
16.
J Paediatr Child Health ; 50(10): E14-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21771153

RESUMO

Noonan syndrome is a common autosomal dominant condition, readily recognisable in childhood. It is characterised by a pattern of typical facial dysmorphism and malformations including congenital cardiac defects, short stature, abnormal chest shape, broad or webbed neck, and a variable learning disability. Mildly affected adults may not be diagnosed until the birth of a more obviously affected child. The phenotype is highly variable. Important progress in understanding the molecular basis of this and other related conditions was made in 2001 when germline mutations in the PTPN11 gene were found to account for ∼50% of cases. Since then, mutations in additional genes in the rat sarcoma (RAS) pathway have been identified in a proportion of the remainder. Molecular confirmation of diagnosis is now possible for many families and has become increasingly important in guiding management. Increased awareness by paediatricians will lead to earlier diagnosis, and provide patients and their families with accurate genetic counselling, including options when planning pregnancy.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Predisposição Genética para Doença , Testes Genéticos/métodos , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/fisiopatologia , Diagnóstico Precoce , Intervenção Educacional Precoce , Feminino , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Noonan/terapia , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida
17.
Congenit Heart Dis ; 9(2): 144-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23750712

RESUMO

OBJECTIVE: Noonan syndrome (NS) is the second most common genetic syndrome associated with cardiac abnormalities, including, most notably, pulmonary stenosis (PS) and hypertrophic cardiomyopathy (HCM). Little is known about the natural history of heart disease in this unique subset of patients. We sought to contribute information on the natural history of NS by looking at how the cardiac disease progresses with time. DESIGN: This is a retrospective review of the medical records of patients with NS seen at our institution between 1963 and 2011. RESULTS: Records were available for 113 patients. Average length of follow-up was 14.16 years (2 months to 44 years, median 12.5 years). Sixty-six percent (75/113) of our patients had PS; within this subset, 57% (43) were classified as mild, 9% (7) moderate, and 33% (25) severe. None of the cases of mild PS worsened with time. All of the severe cases had an intervention, as did some moderate cases. Fourteen percent (16/113) of our patients had HCM; 56% (9/16) were mild, diagnosed at an average age of 3.8 years. Seven of these were stable with time, while one did progress. Forty-four percent (7/16) of cases were classified as severe, diagnosed at an average age of 4.2 months, and all were managed medically, surgically, or both. Our cohort had seven deaths (ages 6 months and 6, 10, 20, 40, 49, and 50 years). CONCLUSION: Mild PS in patients with NS is nonprogressive. Severe, and in some cases moderate, PS will invariably require a therapeutic intervention. It is uncommon for HCM to progress or have new onset beyond early childhood. Prognosis of heart disease in NS is influenced most by the findings on presentation.


Assuntos
Cardiomiopatia Hipertrófica Familiar/diagnóstico , Síndrome de Noonan/diagnóstico , Estenose da Valva Pulmonar/diagnóstico , Adulto , Fatores Etários , Cardiomiopatia Hipertrófica Familiar/genética , Cardiomiopatia Hipertrófica Familiar/mortalidade , Cardiomiopatia Hipertrófica Familiar/terapia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Estimativa de Kaplan-Meier , Kentucky , Masculino , Pessoa de Meia-Idade , Síndrome de Noonan/genética , Síndrome de Noonan/mortalidade , Síndrome de Noonan/terapia , Fenótipo , Prognóstico , Estenose da Valva Pulmonar/genética , Estenose da Valva Pulmonar/mortalidade , Estenose da Valva Pulmonar/terapia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
18.
Rev Pneumol Clin ; 69(5): 260-4, 2013 Oct.
Artigo em Francês | MEDLINE | ID: mdl-23561737
19.
Lancet ; 381(9863): 333-42, 2013 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-23312968

RESUMO

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.


Assuntos
Síndrome de Noonan , Diagnóstico Diferencial , Humanos , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Síndrome de Noonan/terapia , Prognóstico
20.
Endocrinol Metab Clin North Am ; 41(4): 713-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23099266

RESUMO

Turner syndrome (TS) and Noonan syndrome (NS) have short stature as a constant feature; however, both conditions can present clinicians with a challenging array of genetic, cardiovascular, developmental, and psychosocial issues. In recent years, important advances have been achieved in each of these areas. This article reviews these two syndromes and provides updates on recent developments in diagnostic evaluation, growth and development, psychological issues, and treatment options for patients with TS and NS.


Assuntos
Síndrome de Noonan , Síndrome de Turner , Feminino , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/uso terapêutico , Humanos , Masculino , Síndrome de Noonan/complicações , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/fisiopatologia , Síndrome de Noonan/terapia , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/etiologia , Proteínas Recombinantes/uso terapêutico , Síndrome de Turner/complicações , Síndrome de Turner/diagnóstico , Síndrome de Turner/fisiopatologia , Síndrome de Turner/terapia
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