Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Am J Med Genet A ; 173(5): 1219-1225, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28317311

RESUMO

Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy. Only five families with prenatal presentation of IPEX syndrome have been reported. Here, we present two additional prenatal onset cases with novel inherited frameshift pathogenic variants in FOXP3 that generate premature stop codons. Ultrasound findings in the first patient identified echogenic bowel, echogenic debris, scalp edema, and hydrops. In the second patient, ultrasound findings included polyhydramnios with echogenic debris, prominent fluid-filled loops of bowel, and echogenic bowel. These cases further broaden the phenotypic spectrum of IPEX syndrome by describing previously unappreciated prenatal ultrasound findings associated with the disease.


Assuntos
Diferenciação Celular/genética , Diabetes Mellitus Tipo 1/congênito , Diarreia/diagnóstico , Diarreia/genética , Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças do Sistema Imunitário/congênito , Adulto , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Diarreia/fisiopatologia , Feminino , Feto , Fatores de Transcrição Forkhead/imunologia , Mutação da Fase de Leitura , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Humanos , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/fisiopatologia , Masculino , NF-kappa B/genética , Fatores de Transcrição NFATC/genética , Gravidez , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Ultrassonografia Pré-Natal
2.
J Inherit Metab Dis ; 40(6): 823-830, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801758

RESUMO

PRKAG2 encodes the γ2 subunit of AMP-activated protein kinase (AMPK), which is an important regulator of cardiac metabolism. Mutations in PRKAG2 cause a cardiac syndrome comprising ventricular hypertrophy, pre-excitation, and progressive conduction-system disease, which is typically not diagnosed until adolescence or young adulthood. However, significant variability exists in the presentation and outcomes of patients with PRKAG2 mutations, with presentation in infancy being underrecognized. The diagnosis of PRKAG2 can be challenging in infants, and we describe our experience with three patients who were initially suspected to have Pompe disease yet ultimately diagnosed with mutations in PRKAG2. A disease-causing PRKAG2 mutation was identified in each case, with a novel missense mutation described in one patient. We highlight the potential for patients with PRKAG2 mutations to mimic Pompe disease in infancy and the need for confirmatory testing when diagnosing Pompe disease.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Mutação/genética , Pré-Escolar , Feminino , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , Lactente , Recém-Nascido , Masculino
3.
J Pediatr ; 165(3): 490-496.e8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24952712

RESUMO

OBJECTIVE: To measure neurodevelopment at 3 years of age in children with single right-ventricle anomalies and to assess its relationship to Norwood shunt type, neurodevelopment at 14 months of age, and patient and medical factors. STUDY DESIGN: All subjects in the Single Ventricle Reconstruction Trial who were alive without cardiac transplant were eligible for inclusion. The Ages and Stages Questionnaire (ASQ, n = 203) and other measures of behavior and quality of life were completed at age 3 years. Medical history, including measures of growth, feeding, and complications, was assessed through annual review of the records and phone interviews. The Bayley Scales of Infant Development, Second Edition (BSID-II) scores from age 14 months were also evaluated as predictors. RESULTS: Scores on each ASQ domain were significantly lower than normal (P < .001). ASQ domain scores at 3 years of age varied nonlinearly with 14-month BSID-II. More complications, abnormal growth, and evidence of feeding, vision, or hearing problems were independently associated with lower ASQ scores, although models explained <30% of variation. Type of shunt was not associated with any ASQ domain score or with behavior or quality-of-life measures. CONCLUSION: Children with single right-ventricle anomalies have impaired neurodevelopment at 3 years of age. Lower ASQ scores are associated with medical morbidity, and lower BSID-II scores but not with shunt type. Because only a modest percentage of variation in 3-year neurodevelopmental outcome could be predicted from early measures, however, all children with single right-ventricle anomalies should be followed longitudinally to improve recognition of delays.


Assuntos
Deficiências do Desenvolvimento/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Sistema Nervoso/crescimento & desenvolvimento , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
4.
medRxiv ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39281767

RESUMO

Congenital heart defects (CHDs) are the most common structural birth defect and are present in 40-50% of children born with Down syndrome (DS). To characterize the genetic architecture of DS-associated CHD, we sequenced genomes of a multiethnic group of children with DS and a CHD (n=886: atrioventricular septal defects (AVSD), n=438; atrial septal defects (ASD), n=122; ventricular septal defects (VSD), n=170; other types of CHD, n=156) and DS with a structurally normal heart (DS+NH, n=572). We performed four GWAS for common variants (MAF>0.05) comparing DS with CHD, stratified by CHD-subtype, to DS+NH controls. Although no SNP achieved genome-wide significance, multiple loci in each analysis achieved suggestive significance (p<2×10-6). Of these, the 1p35.1 locus (near RBBP4) was specifically associated with ASD risk and the 5q35.2 locus (near MSX2) was associated with any type of CHD. Each of the suggestive loci contained one or more plausible candidate genes expressed in the developing heart. While no SNP replicated (p<2×10-6) in an independent cohort of DS+CHD (DS+CHD: n=229; DS+NH: n=197), most SNPs that were suggestive in our GWASs remained suggestive when meta-analyzed with the GWASs from the replication cohort. These results build on previous work to identify genetic modifiers of DS-associated CHD.

5.
J Vasc Surg ; 51(2): 468-70, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20141966

RESUMO

A 53-year-old woman with no classic risk factors for aneurysm disease presented with the sudden onset of chest pain and dyspnea. A large descending thoracic aortic aneurysm with focal type B dissection was identified and excluded by emergency thoracic endografting. Further postoperative evaluation revealed a history of epistaxis, perioral telangiectasias, hepatic hypervascularity, and a mutation in the gene expressing activin receptor-like kinase 1 (ALK1), leading to a diagnosis of hereditary hemorrhagic telangiectasia. Aortic aneurysms associated with hereditary hemorrhagic telangiectasia are extremely rare, and to our knowledge, this is the first report of thoracic endografting in this patient population.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Telangiectasia Hemorrágica Hereditária/diagnóstico , Receptores de Activinas Tipo II , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/genética , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/genética , Aortografia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/genética , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Am J Cardiol ; 122(8): 1429-1436, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30115424

RESUMO

Patients with the Marfan syndrome (MFS) are at risk for sudden death. The contribution of arrhythmias is unclear. This study examines the prevalence of arrhythmias in children with the MFS and their relation to clinical and/or echocardiographic factors. Data from the Pediatric Heart Network randomized trial of atenolol versus losartan in MFS were analyzed (6 months to 25 years old, aortic root diameter z-score > 3.0, no previous aortic surgery and/or dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE) were defined as ≥10 VE or SVE/hour, or the presence of high-grade ectopy. Three-year composite clinical outcome of death, aortic dissection, or aortic root replacement was analyzed. There were 274 analyzable monitors on unique patients from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant SVE; of these, 2 (1%) had both. None had sustained ventricular or supraventricular tachycardia. VE was independently associated with increasing number of major Ghent criteria (odds ratio [OR] = 2.13/each additional criterion, p = 0.03) and greater left ventricular end-diastolic dimension z-score (OR = 1.47/each 1 unit increase in z-score, p = 0.01). SVE was independently associated with greater aortic sinotubular junction diameter z-score (OR = 1.56/each 1 unit increase in z-score, p = 0.03). The composite clinical outcome (14 events) was not related to VE or SVE (p ≥ 0.3), but was independently related to heart rate variability (higher triangular index). In conclusion, in this cohort, VE and SVE were rare. VE was related to larger BSA-adjusted left ventricular size. Routine ambulatory electrocardiographic monitoring may be useful for risk stratification in select MFS patients.


Assuntos
Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Síndrome de Marfan/complicações , Síndrome de Marfan/fisiopatologia , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/tratamento farmacológico , Atenolol/uso terapêutico , Criança , Pré-Escolar , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Lactente , Losartan/uso terapêutico , Masculino , Estudos Retrospectivos
7.
J Thorac Cardiovasc Surg ; 154(5): 1703-1710.e3, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28734628

RESUMO

OBJECTIVES: Adrenergic receptor (ADR) genotypes have been associated with adverse outcomes in heart failure. Our objective was to evaluate the association of ADR genotypes with post-Norwood outcomes in infants with hypoplastic left heart syndrome (HLHS). METHODS: Infants with HLHS participating in the Pediatric Heart Network Single-Ventricle Reconstruction Trial underwent genotyping for 4 single-nucleotide polymorphisms in 3 ADR genes: ADRB1_231A/G, ADRB1_1165G/C, ADRB2_5318C/G, and ADRA2A_2790C/T. The association of genotype with freedom from serious adverse events (SAEs) (death, transplant, extracorporeal membrane oxygenation, cardiopulmonary resuscitation, acute shunt failure, unplanned reoperations, or necrotizing enterocolitis) during 14 months' follow-up was assessed with Cox regression and the association with post-Norwood complications was assessed with Poisson regression. Models were adjusted for clinical and surgical factors. RESULTS: The study included 351 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 5.6 ± 3.6 days. A total of 152 patients had SAEs during 14-month follow-up including 84 deaths and 10 transplants. ADRA2A_2790CC genotype had lower SAE-free survival compared with CT/TT genotypes during follow-up (Log rank test, P = .02), and this association was independent of clinical and surgical risk factors (adjusted Cox regression, hazard ratio 1.54 [95% confidence interval 1.04, 2.30] P = .033). Post-Norwood complication rate did not differ by genotype. CONCLUSIONS: Infants with HLHS harboring ADR genotypes that are associated with greater catecholamine release or sensitivity had lower event-free survival after staged palliation. Excess catecholamine activation may adversely affect cardiovascular adaptation after the Norwood procedure. Future studies should explore whether targeting adrenergic activation in those harboring risk genotypes can improve outcomes. (ClinicalTrials.gov number NCT00115934).


Assuntos
Síndrome do Coração Esquerdo Hipoplásico , Procedimentos de Norwood/efeitos adversos , Complicações Pós-Operatórias , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Correlação de Dados , Feminino , Seguimentos , Humanos , Síndrome do Coração Esquerdo Hipoplásico/genética , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Recém-Nascido , Masculino , Procedimentos de Norwood/métodos , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/genética , Complicações Pós-Operatórias/terapia , Modelos de Riscos Proporcionais
8.
J. inborn errors metab. screen ; 5: e160060, 2017. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1090922

RESUMO

Abstract Pulmonary arterial hypertension (PAH) is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI). We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA