Síndrome de Noonan e insuficiencia aórtica severa en un paciente adulto / Noonan Syndrome and Severe Aortic Regurgitation in an Adult Patient

Introducción: El síndrome de Noonan es una enfermedad congénita con una incidencia de 1:1000-2500 recién nacidos vivos. Se encuentra subdiagnosticada en nuestro medio debido a la variabilidad clínica, lo cual no permite un adecuado control y seguimiento para detectar complicaciones consecuentes a los defectos cardiovasculares congénitos. En Perú no existen reportes de casos sobre el síndrome de Noonan y sus complicaciones. Objetivo: Discutir la importancia del examen clínico para su adecuado diagnóstico a partir de las características del síndrome de Noonan en un adulto. Caso clínico: Presentamos el caso de un varón de 33 años con síndrome de Noonan, endocarditis infecciosa e insuficiencia aórtica severa. Conclusiones: Se resalta la importancia del examen físico y el uso de criterios diagnósticos para realizar el diagnóstico del síndrome de Noonan(AU)

Introduction: Noonan syndrome is a congenital disease with an incidence of 1: 1000-2500 live newborns. Due to its clinical variability, it is underdiagnosed in our setting, which does not allow adequate control and follow-up to detect complications resulting from congenital cardiovascular defects. In Peru, there are no case reports on Noonan syndrome and its complications. Objective: To discuss the importance of clinical examination for adequate diagnosis of Noonan syndrome, based on the characteristics of the disease in an adult. Clinical case: We present the case of a 33-year-old male patient with Noonan syndrome, infective endocarditis, and severe aortic regurgitation. Conclusions: The importance of physical examination and the use of diagnostic criteria to diagnose Noonan syndrome are highlighted(AU)

Síndrome de Noonan / Noonan syndrome

Se presenta un caso de Síndrome de Noonan, enfermedad genética poco frecuente con manifestaciones clínicas diversas, con una característica afectación cardiovascular como es la estenosis valvular pulmonar. La paciente ingresa en insuficiencia cardiaca y durante la observación se detectan datos clínicos típicamente descritos en la enfermedad, tales como talla baja, hipertelorismo, pterigium coli y tórax carinatum. Se evalúa de manera conjunta con genética y se identifican los criterios diagnósticos. La paciente es compensada y egresada por mejoría

A case of Noonan´s Syndrome, is reported here. This is a rare genetic disease with diverse clinical manifestations, with a characteristic cardiovascular involvement of pulmonary valve stenosis. The patient was admitted with heart failure. Typical clinical features were found such as short stature, hypertelorism, pterygium coli and thorax carinatum. The patient was evaluated with the genetic specialists and diagnostic criteria were identified

Manifestaciones otorrinolaringológicas del síndrome de Noonan / Otorhinolaryngologic manifestations of Noonan síndrome / Manifestações otorrinolaringológicas da síndrome de noonan

El síndrome de Noonan (SN) es un trastorno genético de herencia autosómica dominante relativamente frecuente. Clásicamente se ha descrito como la asociación de talla baja, dismorfias craneofaciales (fundamentalmente hipertelorismo, inclinación hacia abajo de las hendiduras palpebrales, ptosis palpebral, pabellones auriculares rotados y de implantación baja, hélix grueso), cardiopatía congénita (característicamente estenosis pulmonar valvular -EP- y miocardiopatía hipertrófica -MCH-), malformaciones torácicas(pectus excavatum/carinatum, tórax amplio) y criptorquidia en los varones. Tiene una incidencia alta, de 1/1.000- ½.500 neonatos.

Noonan syndrome (NS) is a genetic disorder relatively common autosomal dominant inheritance. Classically described as the association of short stature, craniofacial dysmorphia (hypertelorism, palpebral ptosis, ear low – set ears), congenital heart disease (typically valvular pulmonary stenosis -PSand hypertrophic cardiomyopathy -HCM-), thoracic malformations (pectus excavatum / carinatum, broad chest) and cryptorchidism in men. It has a high incidence of 1 / 1,000- 1 / 2,500 newborns.(1).

A síndrome de Noonan (SN) é um transtorno genético de herança autossômica dominante relativamente frequente. Classicamente, foi descrita como a associação de baixa estatura, dismorfias craniofaciais (fundamentalmente hipertelorismo, inclinação para baixo das fendas palpebrais, ptose palpebral, pavilhões auriculares rotados e de implantação baixa, hélix grosso), cardiopatia congênita (caracteristicamente estenose pulmonar valvular -EP- e miocardiopatia hipertrófica -MCH-), más formações torácicas (pectus excavatum/carinatum, tórax amplo) e criptorquidia nos meninos. (1) Tem uma incidência alta de 1/1.000- ½.500 neo-natos.

Noonan syndrome: An anesthesiologist's perspective.

Noonan syndrome (NS) is one of the most common non chromosomal syndrome presenting to the cardiac anesthesiologist for the management of various cardiac lesions, predominantly pulmonary stenosis (PS) (80%) and hypertrophic obstructive cardiomyopathy (HOCM) (30%). The presence of HOCM in NS makes these children susceptible to acute congestive heart failure due to hemodynamic fluctuations, thus necessitating optimization of drug and fluid therapy, careful conduct of anesthesia and providing adequate analgesia in the perioperative period. We describe a case of four year old boy with NS who presented to us for the management of PS and HOCM. In our case, transesophageal echocardiography (TEE) played a major role in confirmation of the preoperative findings, detection of any new anomalies missed during the preoperative evaluation, intraoperative monitoring and assessment of the adequacy of repair in the immediate postoperative period. TEE provided invaluable help in taking critical surgical decisions, resulting in a favorable outcome.

Doença celíaca associada à tireoidite de Hashimoto e síndrome de Noonan / Celiac disease associated with Hashimoto's thyroiditis and Noonan syndrome

OBJETIVO: Relatar o caso clínico de uma criança portadora de doença celíaca, tireoidite de Hashimoto e síndrome de Noonan. DESCRIÇÃO DE CASO: Menina de dez anos e seis meses, branca, apresentando história de diarreia líquida há cinco meses e "aumento da barriga". Ao exame, mostrava peso de 20.580g (p<3), estatura de 114cm (p<3), hidratada, descorada 2+/4+ e consciente. Presença de fácies triangular, com hipertelorismo ocular aparente, posição antimongoloide das fendas palpebrais, orelhas em abano de baixa implantação, micrognatia, pescoço curto e pectus excavatum. O abdome mostrava-se globoso, flácido, indolor, com hérnia umbilical, fígado a 2cm do rebordo costal direito, linfedema em membro superior direito e edema de membros inferiores. Nos exames subsidiários, havia anemia microcítica e hipocrômica, déficit de proteínas totais, tireoidite de Hashimoto e atraso de cinco anos na idade óssea. Na ultrassonografia abdominal, as alças intestinais estavam levemente dilatadas. Devido ao linfedema e à diarreia crônica, a hipótese inicial foi de linfangiectasia intestinal, confirmada pela biópsia jejunal, que ainda mostrou padrão compatível de doença celíaca. O cariótipo foi 46XX com diagnóstico clínico de síndrome de Noonan. COMENTÁRIOS: As doenças autoimunes se associam; no caso apresentado, a doença celíaca se associou à tireoidite de Hashimoto, possivelmente pela presença de antígenos do sistema HLA. Já a associação de doença celíaca à síndrome de Noonan é muito rara, sendo este o terceiro relato na literatura.

OBJECTIVE: To describe the clinical case of a child with celiac disease, Hashimoto's thyroiditis and Noonan syndrome. CASE DESCRIPTION: A Caucasian girl aged ten years and six months had liquid diarrhea for five months, and a "distended belly". At the physical exam: weight of 20,580g (p<3), length of 114cm (p<3), hydrated, anemic 2+/4+ and conscious. The patient presented triangular facies, apparent ocular hypertelorism, antimongoloid position of the palpebral fissures, ears with low implantation, micrognathia, short neck and pectus excavatum. The abdomen was globular, flaccid and painless; the liver was 2cm below the right costal margin. Lymphedema in right upper limb and lower limb edema was also noted. Laboratory exams showed microcytic and hypochromic anemia, deficit of total proteins, Hashimoto's thyroiditis and a 5-year delay in bone age. Abdominal ultrasonography showed the bowel slightly dilated. Due to lymphedema and chronic diarrhea, the initial hypothesis was intestinal lymphangiectasis, which was confirmed by a jejunal biopsy, which also showed celiac disease. The genetic evaluation revealed a 46XX karyotype and a clinical diagnosis of Noonan syndrome. COMMENTS: Different autoimmune diseases can be associated. In this case, the celiac disease and the Hashimoto's thyroiditis are possibly related to the presence of HLA system antigens. However, the association of the celiac disease with the Noonan syndrome is very rare, and this is the third report in the literature.

Hipoacusia neurosensorial en un síndrome de Noonan y secuencia Poland / Neurosensory hypoacusis in a Noonan's syndrome and Poland's sequence

Se calcula que el 50 por ciento de los casos de sordera profunda en la infancia puede ser de origen genético. Se presenta el caso de un niño de 9 años, atendido en los Servicios de Otorrinolaringología y Genética del Hospital Pediátrico Docente William Soler, por presentar hipoacusia neurosensorial grave unilateral y displasia congénita de Mondini en el oído izquierdo, del lado contrario a la hipoplasia del músculo pectoral mayor, lo cual coincide con un síndrome de Noonan y secuencia de Poland, que resulta de especial interés. Se constató la hipoacusia con audiometría tonal y potencial evocado auditivo de tallo cerebral. En la tomografía del oído se observó una hipoplasia coclear con agenesia de la espira apical. Se destacan las manifestaciones clínicas y la importancia del estudio otológico e imaginólogico en el diagnóstico de la pérdida auditiva

It is estimated that the 50 percent of cases of deep deafness during childhood may be or genetic origin. This is the case of a child aged 9 seen in Otorhinolaryngology and Genetics Services of the Wiliam Soler Teaching Children Hospital due to a unilateral severe neurosensory hypoacusis and Mondini's congenital dysplasia in left ear contralateral to the major pectoral muscle hypoplasia, an interesting situation. Hypoacusis was confirmed using tone audiometry and auditory evoked potential of brain stem. Ear tomography demonstrated a cochlear hypoplasia with agenesis of apical spiral. The clinical manifestations and the significance of the ontological and imaging study in diagnosis of auditory loss are emphasized

Candida albicans meningitis in an infant with noonan syndrome

Noonan syndrome is a rare disorder, characterized by several malformations such as dysplasia and stenosis of the pulmonary valve, atrial septal defect and a typical pattern of hypertrophic cardiomyopathy. We describe here a 1-month old girl, who was referred to our center with seizure and apnea. She had wide anterior fontanel, head circumference and sunset eye. Intaventricular hemorrhage by sonography and atrial septal defect and hypertrophy cardiomyopathy by echocardiography were detected. Clinical and laboratory findings of the patient were compatible with a diagnosis of Noonan syndrome, which was also confirmed by molecular analysis. Candida albicans was grown in the blood and cerebrospinal fluid cultures. Treatment with Amphotrycine B was started for the patient and she responded well to this therapy. Early diagnosis and appropriate diagnosis of a rare condition in the patient with such rare disease are the main keys to avoid further complications and even death of patient.

Variabilidade do fenótipo de pacientes com síndrome de Noonan com e sem mutações no gene PTPN11 / Phenotype variability in Noonan syndrome patients with and without PTPN11 mutation

INTRODUÇÃO: Aproximadamente 50 por cento dos pacientes com síndrome de Noonan (SN) apresentam mutações em heterozigose no gene PTPN11. OBJETIVO: Avaliar a freqüência de mutações no PTPN11 em pacientes com SN e analisar a correlação fenótipo-genótipo. PACIENTES: 33 pacientes com SN. MÉTODO: Extração de DNA de leucócitos periféricos e seqüenciamento dos 15 exons do PTPN11. RESULTADOS: Nove diferentes mutações missense no PTPN11, incluindo a mutação P491H, ainda não descrita, foram encontradas em 16 dos 33 pacientes. As características clínicas mais freqüentes dos pacientes com SN foram: pavilhão auricular com rotação incompleta e espessamento da helix (85 por cento), baixa estatura (79 por cento), prega cervical (77 por cento) e criptorquidismo nos meninos (60 por cento). O Z da altura foi de -2,7 ± 1,2 e o do IMC foi de -1 ± 1,4. Os pacientes com mutação no PTPN11 apresentaram maior freqüência de estenose pulmonar do que os pacientes sem mutação (38 por cento vs. 6 por cento, p< 0,05). Pacientes com ou sem mutação no PTPN11 não diferiram em relação à média do Z da altura, Z do IMC, freqüência de alterações torácicas, características faciais, criptorquidia, retardo mental, dificuldade de aprendizado, pico de GH ao teste de estímulo e Z de IGF-1 ou IGFBP-3. CONCLUSÃO: Identificamos mutações no PTPN11 em 48,5 por cento dos pacientes com SN, os quais apresentaram maior freqüência de estenose pulmonar.

INTRODUCTION: Around 50 percent of Noonan syndrome (NS) patients present heterozygous mutations in the PTPN11 gene. AIM: To evaluate the frequency of mutations in the PTPN11 in patients with NS, and perform phenotype-genotype correlation. PATIENTS: 33 NS patients (23 males). METHODS: DNA was extracted from peripheral blood leukocytes, and all 15 PTPN11 exons were directly sequenced. RESULTS: Nine different missense mutations, including the novel P491H, were found in 16 of 33 NS patients. The most frequently observed features in NS patients were posteriorly rotated ears with thick helix (85 percent), short stature (79 percent), webbed neck (77 percent) and cryptorchidism (60 percent) in boys. The mean height SDS was -2.7 ± 1.2 and BMI SDS was -1 ± 1.4. Patients with PTPN11 mutations presented a higher incidence of pulmonary stenosis than patients without mutations (38 percent vs. 6 percent, p< 0.05). Patients with and without mutations did not present differences regarding height SDS, BMI SDS, frequency of thorax deformity, facial characteristics, cryptorchidism, mental retardation, learning disabilities, GH peak at stimulation test and IGF-1 or IGFBP-3 SDS. CONCLUSION: We identified missense mutations in 48.5 percent of the NS patients. There was a positive correlation between the presence of PTPN11 mutations and pulmonary stenosis frequency in NS patients.

Manifestaciones clínicas más frecuentes en pacientes con sindrome de Turner del Instituto de Genética, La Paz-Bolivia período 1990 - 2004 / Most frequent clinical features of patients whit Turner syndrome in the Instituto de Genética La Paz - Bolivia, From 1990 - 2004

Objetivo. Identificar los signos clínicos más frecuentes en pacientes con Síndrome de Turner.Diseño Corte transversal. Lugar: Instituto de Genética; La Paz, Bolivia.Población 36 pacientes con diagnóstico citogenético. Métodos: Recolección de datos clínicos de pacientes con Síndrome de Turner períodos 1990-2004. Se excluyeron pacientes que presentaban similares fenotipos y con cariotipo no compatible. Resultados: Manifestaciones clínicas más frecuentes: baja talla proporcionada 77.8%, disgenesia gonadal 61.1%, pterigium colli 27.8%, displasia de pabellones auriculares 33.3%. La edad de diagnóstico corresponde: < 5años 11.1%, entre 10 a 14 años 44.4%. Citogeneticamente el 72% fueron 45 X0, 28% mosaicos. Conclusión: Clínicamente el Síndrome de Turner es variable, y es diagnosticado más frecuentemente durante la adolescencia, etapa en la que se perdieron oportunidades para un adecuado tratamiento que coadyuve a prevenir complicaciones.El fenotipo de esta cromosomopatía actualmente a sido relacionado con mutaciones de genes como RPS4X y SOS.

Objective. Identify the most frequents clinical Turner syndrome patients features. Design Cross section. Place Genetic Institute, La Paz, Bolivia. Participants 36 patients with Turner Syndrome. Methods Clinical features data were collected from Genetic Institute records. Patients with similar clinical features with out cariotyping diagnosis where not included. Results We find small stature 77.8%, gonads dysgenesis 61.1%, pterigium colli 27.8%, anomalous auricles 33.3%. Age of diagnosis was less than 5 years 11.1%, between to 10 to 14 years 44.4%. Cytogenetic analysis report monosomy in 72% , mosaics (28%). Conclusions The clinical features of Turner Syndrome are variable, the diagnosis it's most frequency during puberty, age where could it be late to prevent consequences. The phenotype of Turner Syndrome has been related to RPS4X and SOS genes.

Anterior uveitis and congenital fibrosis of the extraocular muscles in a patient with Noonan syndrome.

We describe a patient with Noonan syndrome who presented with Human Leukocyte Antigen B27-associated recurrent acute anterior uveitis and manifestations of congenital fibrosis of the extraocular muscles, which has not been reported before.

Hematological findings in Noonan syndrome

OBJECTIVE: Noonan syndrome is a multiple congenital anomaly syndrome, and bleeding diathesis is considered part of the clinical findings. The purpose of this study was to determine the frequency of hemostatic abnormalities in a group of Noonan syndrome patients. METHOD: We studied 30 patients with clinical diagnosis of Noonan syndrome regarding their hemostatic status consisting of bleeding time, prothrombin time, activated partial thromboplastin time and thrombin time tests, a platelet count, and a quantitative determination of factor XI. RESULTS: An abnormal laboratory result was observed in 9 patients (30 percent). Although coagulation-factor deficiencies, especially factor XI deficiency, were the most common hematological findings, we also observed abnormalities of platelet count and function in our screening. CONCLUSIONS: Hemostatic abnormalities are found with some frequency in Noonan syndrome patients (30 percent in our sample). Therefore, we emphasize the importance of a more extensive hematological investigation in these patients, especially prior to an invasive procedure, which is required with some frequency in this disorder

Neurofibromatosis-Noonan syndrome or LEOPARD Syndrome? A clinical dilemma.

Neurofibromatosis (NF), Noonan syndrome (NS), and LEOPARD syndrome are all autosomal dominant conditions, each being a distinct clinical entity by itself. Rarely, one encounters cases with features of NF and NS and is termed as the 'Neurofibromatosis-Noonan syndrome' (NF-NS). The authors report a clinical dilemma with major clinical features of the NF-NS syndrome and LEOPARD syndrome co-existing in the same patient. Also, features of Noonan syndrome and LEOPARD syndrome are compared with the case reported.

Noonan syndrome: a clinical and genetic study of 31 patients

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71 percent); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87 percent); cardiac anomalies (65 percent), and fetal pads in fingers and toes (70 percent). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic

Síndrome de Noonan: Estudo clínico-genético de 30 pacientes / Noonan syndrome: clinical-genetic study of 30 patients

A síndrome de Noonan (SN), entidade genética de herança autossômica dominante, subdiagnosticada em funçäo da expressividade extremamente variável do quadro clínico, é possivelmente uma das síndromes mendelianas mais freqüentes. Em um estudo prospectivo foram avaliados 30 pacientes a partir de um protocolo de investigaçäo clínico-laboratorial. Entre os critérios clínicos descritos na SN os mais importantes para o diagnóstico foram: ptose palpebral, micrognatia, fendas anti-down, raiz nasal deprimida, base nasal larga, hipertelorismo mamilar, criptorquidia e ptergium colli. Retardo mental era presente ou questionável em 14 pacientes. Os achados laboratoriais mais freqüentes foram: cardiopatia (predominando estenose pulmonar e comunicaçäo inter-atrial), anomalias renais, atraso de idade óssea, anomalias de coluna cervical, alteraçöes oftalmológicas, alteraçöes de audiçäo e coagulograma alterado. Apenas três pacientes (10 porcento) apresentaram displasia linfática, sugerindo possivelmente uma mortalidade aumentada neste grupo. Dois pacientes têm a reconhecida associaçäo da SN com neurofibromatose. Dois casos familiais foram confirmados e há nove casos familiais suspeitos. A idade paterna avançada nos casos näo familiais seria compatível com a mutaçäo nova para gen autossômico dominante. Os dados apresentados ressaltam a importância da sistematizaçäo do protocolo de investigaçäo e acompanhamento, visando a antecipaçäo e prevençäo de complicaçöes, bem como subsídios para o aconselhamento genético