RESUMEN
Background and Objectives: Tachycardia is a common cardiovascular disease. Drugs blocking ß1-adrenergic receptors (ADRB1) are used in the therapy of arrhythmogenic heart diseases. Disease-related polymorphisms can be observed within the ADRB1 gene. The two most important are Ser49Gly and Arg389Gly, and they influence the treatment efficacy. The family of the cytochrome P450 system consists of the isoenzyme CYP2D6 (Debrisoquine 4-hydroxylase), which is involved in phase I metabolism of almost 25% of clinically important drugs, including antiarrhythmic drugs. A study was conducted to detect the ADRB1 and CYP2D6 gene polymorphisms. Materials and Methods: The material for the test was whole blood from 30 patients with ventricular and supraventricular tachycardia and 20 controls. The samples were obtained from the Department of Pediatric Cardiology. The first to be made was the extraction of DNA using a GeneMATRIX Quick Blood DNA Purification Kit from EURx. The selected ADRB1 and CYP2D6 gene polymorphisms were detected by high-resolution melting polymerase chain reaction (HRM-PCR) analysis. Results: Based on the analysis of melt profile data for each PCR product, the identification of polymorphisms was carried out. Heterozygotes and homozygotes were found in the examined alleles. Conclusions: The frequency of the Arg389Gly polymorphism differs statistically significantly between the control group and patients with supraventricular and ventricular arrhythmias, as well as between these two groups of patients. Moreover, the Arg389Gly polymorphism was statistically more prevalent in the group of girls with SVT arrhythmia compared to girls with VT. A few carriers of homozygous and heterozygous systems of the S49G polymorphism were detected among patients with arrhythmias, as well as control group. The percentage of individuals carrying the CYP2D6 4 allele as either homozygous or heterozygous was observed in the study and control groups. The high prevalence of the CYP2D6*4 allele carriers in both groups prompts the optimization of beta-1 blocker therapy.
Asunto(s)
Antagonistas Adrenérgicos beta , Citocromo P-450 CYP2D6 , Niño , Femenino , Humanos , Antagonistas Adrenérgicos beta/uso terapéutico , Arritmias Cardíacas/genética , Citocromo P-450 CYP2D6/genética , ADN , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 1/genéticaRESUMEN
PURPOSE: Aberrant expression of various miRNA species has been implicated in numerous cardiac diseases, e.g., heart failure, hypertrophy, conduction disturbances, and arrhythmogenesis. The aim of this study was to determine whether miR-1, miR-133a, and miR-133b can serve as biomarkers in the diagnosis of ventricular (Va) and supraventricular (SVa) arrhythmias in pediatric patients. MATERIALS AND METHODS: Molecular analysis included 30 patients with SVa or Va (13-17.5 years; 14 boys/16 girls) and 20 non-arrhythmic controls. Arrhythmia was confirmed by 24-h Holter ECG recording. miRNA was extracted from serum using the miRNeasyR Serum/Plasma Kit. miScript SYBR Green PCR Kit (Qiagen) was used to quantify miRNA expression. RESULTS: The levels of miR-1 and miR-133a expression were significantly higher in the SVa group than in the controls (p â= â0.0327 and p<0.0001, respectively). Additionally, both groups of patients with arrhythmia presented significantly lower expression levels of miR-133b than the controls (p<0.01 for both comparisons). The level of miR-133a expression in the SVa group was significantly higher than in the Va group (p â= â0.0124). ROC analysis demonstrated that the expressions of miR-1 and miR-133a could differentiate between the SVa patients and arrhythmia-free controls (AUC â= â0.7091, p â= â0.07 and AUC â= â0.8021, p â= â0.007, respectively). Furthermore, the expression of miR-133b was shown to distinguish patients with SVa and Va from the arrhythmia-free controls (AUC â= â0.7273, p â= â0.07 and AUC â= â0.8030, p â= â0.04, respectively). CONCLUSIONS: miR-1, miR-133a, and miR-133b have the potential to become diagnostic biomarkers of arrhythmia in pediatric patients.
Asunto(s)
MicroARN Circulante , MicroARNs , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Biomarcadores , Niño , MicroARN Circulante/genética , Femenino , Humanos , Masculino , MicroARNs/genética , Curva ROCRESUMEN
BACKGROUND: T-wave parameters, especially the Tpeak-Tend interval (TpTe), reflect the total dispersion of repolarization, whose amplification may lead to the development of life-threatening ventricular arrhythmias observed in the long QT syndrome (LQTS). OBJECTIVES: The study attempted to evaluate QT, QTp (Q-Tpeak) and TpTe (Tpeak-Tend) intervals in unaffected and affected blood relatives of children with clinically confirmed LQTS as well as to determine whether the values of these repolarization parameters may be used in clinical practice. MATERIAL AND METHODS: The study group included 47 affected blood relatives (27 LQTS1 and 20 LQTS2) and 68 unaffected family members without clinically confirmed LQTS symptoms. The TpTe, QT and QTp intervals were measured manually in the lead V5 of standard ECGs and corrected using Bazett's and Fridericia's formulas. RESULTS: The RR, QT, QTp and TpTe intervals with their corrected values were significantly longer (p < 0.0001) in the affected subjects than in the unaffected subjects and, similarly, in LQTS1 and LQTS2 patients compared with the unaffected family members. The TpTe interval in LQTS2 showed only a tendency to be longer compared to LQTS1, but did not reach statistical significance (p = 0.0933). For affected blood relatives, only the TpTe interval (p < 0.0409) and QT interval, corrected with Bazett's (p < 0.0393) and Fridericia's (p < 0.0495) formulas, enabled differentiation between LQTS1 (mean TpTe = 103 ±15) and LQTS2 women (mean TpTe = 106 ±17). Moreover, there were statistically significant differences (p < 0.05) in the TpTe interval between the 6 sex subgroups: unaffected women and men as well as women and men with LQTS1 and LQTS2. CONCLUSIONS: The electrocardiographic Tpeak-Tend parameter, in addition to the QT interval, is helpful in identifying affected blood relatives of children with LQTS, particularly for the group of LQTS1 and LQTS2 women. Further studies are required to assess the clinical importance of the TpTe interval in families with long QT syndrome.
Asunto(s)
Arritmias Cardíacas/fisiopatología , Electrocardiografía/métodos , Familia , Síndrome de QT Prolongado/diagnóstico , Niño , Femenino , Humanos , MasculinoRESUMEN
Compared to conventional echocardiography, spectral tissue Doppler imaging (s-TDI) allows more precise evaluation of diastolic cardiac function. The purpose of this study was to conduct s-TDI to analyze the slow movement of the left ventricular (LV) myocardium in adolescents with systemic arterial hypertension (HT) and to determine whether patients with HT suffer from LV diastolic dysfunction. The study group comprised 69 consecutive patients (48 boys and 21 girls aged 14-17 years [mean, 15.5â±â1.1 years]) with primary HT, and the control group comprised 48 healthy participants (24 boys and 24 girls aged 14-17 years [mean, 15.8â±â1.3 years]). Physical examinations, 24-hour arterial blood pressure monitoring, conventional 2-dimensional and Doppler echocardiography, and s-TDIs were performed. Analysis revealed that study group participants were significantly heavier and had greater LV mass indices than controls (Pâ<â0.001). There were no differences between the velocities of E waves (peak early filling of mitral inflow), but the deceleration times of the mitral E waves were significantly shorter whereas the A waves survived longer in the study group than in the control group. The velocities of A waves (peak late filling of mitral inflow) were elevated (Pâ=â0.041), and the E/A wave pattern (E/Aâ=â1.8â±â0.4) was normal. These results suggest pseudonormalization, a type of LV diastolic dysfunction in adolescents with HT.In the study group, when the sample volume was positioned at the septal or lateral insertion site of the mitral leaflet, the e' wave velocity was significantly depressed whereas the a' wave velocity was elevated, compared to those of the control group (Pâ<â0.001).The e'/a' ratios from the septal and lateral insertion sites were lower, whereas the E/e' ratio from the septal insertion site was significantly higher in the study group, similar to that seen in atrial reversal velocity (Pâ<â0.001).These findings indicate that using sTDI to find and measure diastolic LV failure is valuable when the probe is placed at the septal and lateral mitral valve annuli during examination.Changes in the myocardium appear similar to those seen in adults.
Asunto(s)
Ecocardiografía Doppler/métodos , Hipertensión/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adolescente , Presión Sanguínea , Estudios Transversales , Hipertensión Esencial , Femenino , Humanos , Masculino , PoloniaAsunto(s)
Citocromo P-450 CYP2C9/genética , Síndrome de QT Prolongado/tratamiento farmacológico , Polimorfismo Genético , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia de los Genes , Humanos , Síndrome de QT Prolongado/enzimología , Síndrome de QT Prolongado/genética , Losartán/administración & dosificación , Losartán/farmacocinética , Losartán/uso terapéutico , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Warfarina/administración & dosificación , Warfarina/farmacocinética , Warfarina/uso terapéuticoRESUMEN
Congenital long-QT syndrome is a genetic disorder associated with abnormalities in the function and/or structure of cardiac ion channels. Up to the present, 13 types of the disease have been described (LQTS1-13) which result from the fact that 13 genes of which mutations can have an influence on the occurrence of the disease have been identified. Characteristic symptoms of the disease include the changes in the ECG (QT interval prolonged above 450 ms), "torsade de pointes," fainting, and even sudden cardiac death. The present study has been focused on two types of the disease, namely, LQTS1 and LQTS2. The examination of two appropriate genes expression (KCNQ1; KCNH2) at the transcription level by QRT-PCR in a group of LQTS patients and a healthy control group showed different transcriptional activities of KCNH2 gene in LQTS2 patients compared to the control individuals. KCNQ1 gene expression study did not reveal such differences between both groups. The results indicate that QRT-PCR may serve as a complimentary method to the identification of molecular alterations in genetic determinants of LQTS2 only, but it cannot be used as a sole diagnostic criterion.
Asunto(s)
Canales de Potasio Éter-A-Go-Go/genética , Canal de Potasio KCNQ1/genética , Síndrome de QT Prolongado/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Proteínas de Unión al ADN , Canal de Potasio ERG1 , Femenino , Regulación de la Expresión Génica , Humanos , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/patología , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
The opportunity to distinguish an accurate set of genes associated with multigenic diseases such as cardiomyopathies or cardiac arrhythmias was very limited before the genomic era. Numerous methods of measuring RNA abundance exist, including northern blotting, multiplex polymerase chain reaction (PCR), and quantitative real-time reverse transcriptase-PCR. However, these techniques might be used to assess the expression levels of only 10-50 genes at time. Today, DNA microarrays provide us with opportunity to simultaneously analyze tens of thousands of genes, giving a remarkable possibility to investigate the genomic contribution to cardiovascular diseases. A particular tissue at any stage of health or disease may be used to generate a genomic profile. Microarray techniques are already used in infectious diseases, oncology, and pharmacology to facilitate clinicians, risk-stratify patients, as well as to predict and assess therapeutic responses to drugs. In this paper, we describe recent advances in the use of various types of microarray technique in the diagnosis of arrhythmogenic heart disease. We also highlight other strategies and methods of differential gene typing comparing with pros and cons of microarray analysis.
Asunto(s)
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/metabolismo , Biomarcadores/análisis , Perfilación de la Expresión Génica/métodos , Metaboloma , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Predicción , Perfilación de la Expresión Génica/tendencias , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/tendenciasRESUMEN
The Department of Pediatric Cardiology, Medical University of Silesia in Katowice-Ligota, studied 24 patients with clinically diagnosed (using ECG) long-QT syndrome (LQTS) in 18 cases. Nine patients were diagnosed with LQT1 and nine with LQT2. The other six individuals were healthy, with no symptoms characteristic for prolonged QT syndrome, but came from families with confirmed disease occurrence. The study was conducted on members of four families. In order to search for mutations (using mSSCP and sequencing), genomic DNA was obtained from patients to determine the expression levels of the genes KCNQ1 and KCNH2 (HERG), involved in the occurrence of clinical signs of disease. Total RNA was extracted from peripheral blood. Consent to the use of blood samples of patients had been given by the Bioethics Commission of the Medical University of Silesia. mSSCP analysis and sequencing did not confirm the occurrence of mutations in KCNQ1 and HERG associated with the occurrence of LQTS. Analysis of gene expression profile of KCNQ1 and HERG confirmed the presence of disease in people with a known clinical diagnosis. Overexpression, as well as reduced expression, was observed for the examined genes. KCNQ1 was inhibited in two families, whereas HERG was reduced in one and overexpressed in the other. Gene expression profile analysis showed abnormal expressions of KCNQ1 and HERG in healthy subjects, which may be a sign of predisposition to develop the disease. The novelty of our study involved the use of total mRNA isolated from human peripheral blood, and the very limited evidence in the literature to date regarding the assessment of gene expression profile of HERG and KCNQ1 in relation to the presence of prolonged QT syndrome.
Asunto(s)
Canales de Potasio Éter-A-Go-Go/genética , Pruebas Genéticas , Canal de Potasio KCNQ1/genética , Síndrome de QT Prolongado/diagnóstico , Mutación , Síndrome de Romano-Ward/diagnóstico , Adolescente , Adulto , Anciano , Niño , Análisis Mutacional de ADN , Canal de Potasio ERG1 , Electrocardiografía , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Humanos , Síndrome de QT Prolongado/congénito , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Polonia , Valor Predictivo de las Pruebas , ARN Mensajero/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Síndrome de Romano-Ward/genética , Síndrome de Romano-Ward/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: The KCNQ1 and HERG genes mutations are responsible for specific types of congenital long QT syndrome (LQT). AIM: To examine the expression of KCNQ1 and HERG genes that encode potassium channels (rapid and slow) responsible for the occurrence of particular types of LQT syndrome. The study also attempted to prove that beta-actin is a good endogenous control when determining the expression of the studied genes. METHODS: The study enrolled six families whose members suffered from either LQT1 or LQT2, or were healthy. Examination of gene expression was achieved with quantitative PCR (QRT-PCR). Expression of the investigated genes was inferred from the analysis of the number of mRNA copies per 1 mg total RNA isolated from whole blood. On the basis of KCNQ1 gene expression profile, the presence of, or absence of, LQT1 could be confirmed. RESULTS AND CONCLUSIONS: The study revealed a statistically significant difference (p = 0.031) between the number of KCNQ1 gene copies in patients and healthy controls. On the basis of HERG (KCNH2) gene expression profile, patients with LQT2 cannot be unequivocally differentiated from healthy subjects (p = 0.37).
Asunto(s)
Canales de Potasio Éter-A-Go-Go/genética , Canal de Potasio KCNQ1/genética , Síndrome de QT Prolongado/genética , Mutación , Actinas , Adolescente , Adulto , Anciano , Niño , Preescolar , Canal de Potasio ERG1 , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Lactante , MasculinoRESUMEN
INTRODUCTION: The main goal of this study was to examine the patient age and sex dependent expression of KCNQ1 and HERG genes that encode potassium channels responsible for the occurrence of long QT syndrome (LQTS). MATERIAL AND METHODS: The study enrolled 43 families whose members suffered from LQTS type 1 (LQTS1) or 2 (LQTS2) or were healthy. The study attempted to prove that ß-actin is a good endogenous control when determining the expression of the studied genes. Examination of gene expression was achieved with quantitative real-time PCR (QRT-PCR). Expression of the investigated genes was inferred from the analysis of the number of mRNA copies per 1 µg total RNA isolated from whole blood. RESULTS: Significantly lower KCNQ1 and KCNH2 mRNA levels in healthy females than healthy males were observed (p = 0.032; p = 0.02). In male patients both transcripts were expressed at a lower level (p = 0.0084; p = 0.035). The comparison of transcriptional activity of KCNQ1 and KCNH2 in healthy adults and children revealed higher KCNQ1 and lower KCNH2 mRNA levels in healthy adults (p = 0.033; p = 0.04), higher KCNQ1 and lower KCNH2 mRNA levels in adult patients below 55 years old than in adults over 55 years old (p=0.036; p = 0.044), and significantly higher KCNQ1 and lower KCNH2 mRNA levels in adult patients (over 55 years) than in paediatric patients (below 15 years) (p=0.047; p = 0.08). CONCLUSIONS: The results support the hypothesis that KCNQ1 and HERG gene expression is influenced by age and gender in human patients with long QT syndrome and in healthy subjects.
RESUMEN
BACKGROUND: Mitral valve prolapse (MVP) is the most common primary valvular abnormality in a young population. In some individuals, MVP is silent or associated with palpitations, dizziness, chest pain, and abnormal electrocardiogram (ECG) repolarization with or without ventricular arrhythmias. HYPOTHESIS: The aim of the present study was to assess the occurrence of the clinical and electrocardiographic abnormalities in young athletes with silent MVP. METHODS: A group of 10 children, who have been sport training intensively, with preparticipation silent MVP were examined for symptoms and/or ECG abnormalities. The diagnosis of MVP was made by echocardiography. RESULTS: Three athletes were asymptomatic at initial presentation. The other 7 athletes presented with symptoms. The QTc intervals > 440 msec were recorded in 2 athletes (1 with syncope). Abnormal ECG repolarization was found in 7 athletes (4 athletes were symptomatic and 3 were asymptomatic). A large variety of T-waves was registered in athletes who presented with symptoms. In asymptomatic athletes, the tall and flat T-waves were recorded. CONCLUSIONS: Young athletes with MVP are often predisposed to electrocardiographic abnormalities of ventricular repolarization, which requires annual cardiologic evaluation.
Asunto(s)
Arritmias Cardíacas/etiología , Muerte Súbita Cardíaca/etiología , Electrocardiografía , Prolapso de la Válvula Mitral/diagnóstico , Deportes , Potenciales de Acción , Adolescente , Factores de Edad , Arritmias Cardíacas/fisiopatología , Dolor en el Pecho/etiología , Dolor en el Pecho/fisiopatología , Niño , Ecocardiografía Doppler , Fatiga/etiología , Fatiga/fisiopatología , Femenino , Cefalea/etiología , Cefalea/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Cinética , Masculino , Prolapso de la Válvula Mitral/complicaciones , Prolapso de la Válvula Mitral/fisiopatología , Valor Predictivo de las Pruebas , Síncope/etiología , Síncope/fisiopatologíaRESUMEN
This review discusses the risk of cardiac events and genotype-based management of LQTS. We describe here the genetic background of long QT syndrome and the eleven different genes for ion-channels and a structural anchoring protein associated with that disorder. Clinical Background section discusses the risk of cardiac events associated with different LQTS types. Management and Prevention section describes in turn gene-specific therapy, which was based on the identification of the gene defect and the dysfunction of the associated transmembrane ion channel. In patients affected by LQTS, genetic analysis is useful for risk stratification and for making therapeutic decisions. A recent study reported a quite novel pathogenic mechanism for LQTS and suggested that treatments aimed at scaffolding proteins rather than specific ion channels may be an alternative to antiarrhythmic strategy in the future.
Asunto(s)
Predisposición Genética a la Enfermedad , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/terapia , Antagonistas Adrenérgicos beta/uso terapéutico , Estimulación Cardíaca Artificial , Terapia Combinada , Desfibriladores Implantables , Femenino , Ganglionectomía/métodos , Genotipo , Humanos , Síndrome de QT Prolongado/mortalidad , Masculino , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
Isolated noncompaction of the ventricular myocardium (INVM) sometimes referred to as spongy myocardium is a rare, congenital and also acquired cardiomyopathy. It appears to divide the presentation into neonatal, childhood and adult forms of which spongy myocardium and systolic dysfunction is the commonality. The disorder is characterized by a left ventricular hypertrophy with deep trabeculations, and with diminished systolic function, with or without associated left ventricular dilation. In half or more of the cases, the right ventricle is also affected. The sporadic type, however, in some patients, may be due to chromosomal abnormalities and the occurrence of familial incidence. Isolated noncompaction of the left ventricular myocardium in the majority of adult patients is an autosomal dominant disorder. The familial and X-linked disorders have been described by various authors. We here describe the genetic background of this disorder: some of the most mutated genes that are responsible for the disease are (G4.5 (tafazzin gene): alpha-dystrobrevin gene (DTNA); FKBP-12 gene; lamin A/C gene; Cypher/ZASP (LIM, LDB3) gene); and some genotype-phenotype correlations (Becker muscular dystrophy, Emery-Dreifuss muscular dystrophy or Barth syndrome) based on the literature review.
Asunto(s)
Cardiomiopatías/genética , Heterogeneidad Genética , Ventrículos Cardíacos , Humanos , Mutación/genéticaRESUMEN
We describe the clinical and genetic characteristics of the family, in which the diagnosis of LQT1 had been made. The electrocardiogram (ECG) characteristics of this patient indicated the likelihood of LQTS1. Polymorphic ventricular extrasystolies and episodes of polymorphic non-sustained ventricular tachycardia were confirmed by Holter ECG monitoring. On the exertional electrocardiogram polymorphic ventricular tachycardia (torsade de pointes) was recorded. Direct sequencing of both DNA strands revealed the absence of mutations or polymorphisms in the KCNQ1, HERG, and SCN5A genes.
Asunto(s)
Electrocardiografía/métodos , Pruebas Genéticas/métodos , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/genética , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Femenino , Predisposición Genética a la Enfermedad/genética , HumanosRESUMEN
Arrhythmogenic right ventricular dysplasia (ARVD) is a complex arrhythmogenic cardiomyopathy, characterized by a partial or total replacement of the right ventricular myocytes by fatty and fibrous tissue. In this study, we present a case of ARVD in 17 year old girl, who was admitted to the hospital after syncope with ventricular arrhythmia. The echocardiography did not demonstrate structural cardiac abnormalities but the magnetic resonance recently showed thinning of the right ventricular wall. The girl was treated with the lidocaine, amiodarone and next, after radiofrequency catheter ablation she was receiving metoprolol. The girl has remained asymptomatic for four years of follow-up.
Asunto(s)
Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/terapia , Adolescente , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Ablación por Catéter , Terapia Combinada , Diagnóstico Diferencial , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Lidocaína/uso terapéutico , Imagen por Resonancia Magnética , Metoprolol/uso terapéuticoRESUMEN
Arrhythmogenic right ventricular dysplasia (ARVD) is a clinical and pathologic entity whose diagnosis rests on electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular (RV) free wall. There is a familial occurrence in about 50% of cases, with autosomal dominant inheritance with variable penetrance and polymorphic phenotypic expression, and is one of the major genetic causes of juvenile sudden death. When the dysplasia is extensive, it may represent the extensive form of ARVCM (arrhythmogenic right ventricular cardiomyopathy). In this review, we focus on the some candidate genes mutations and information on some genotype-phenotype correlation in the ARVD. Our findings are in agreement with those of European Society of Cardiology who stated that: genetic analysis is usefull in families with RV cardiomyopathy because whenever a pathogenetic mutation is identified, it becomes possible to establish a presymptomatic diagnosis of the disease among family members and to provide them with genetic counseling to monitor the development of the disease and to assess the risk of transmitting the disease offspring. On the basis of current knowledge, genetic analysis does not contribute to risk stratification of arrhythmogenic RV cardiomyopathy.
Asunto(s)
Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/genética , Mutación/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Muerte Súbita Cardíaca , Desmina/genética , Desmocolinas/genética , Desmogleínas/genética , Desmoplaquinas/genética , Humanos , Proteínas con Dominio LIM , Placofilinas/genética , Proteínas Tirosina Fosfatasas/genética , Receptores de Laminina/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Factor de Crecimiento Transformador beta3/genéticaAsunto(s)
Cardiomiopatías/genética , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/genética , Aciltransferasas , Cardiomiopatías/diagnóstico , Cardiomiopatías/tratamiento farmacológico , Preescolar , Cromosomas Humanos/genética , Proteínas Asociadas a la Distrofina/genética , Femenino , Estudios de Seguimiento , Enfermedades Genéticas Congénitas/tratamiento farmacológico , Enfermedades Genéticas Congénitas/fisiopatología , Cardiopatías Congénitas/tratamiento farmacológico , Cardiopatías Congénitas/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Lactante , Intrones/genética , Lamina Tipo A/genética , Masculino , Mutación Missense , Proteínas/genética , Sitios de Empalme de ARN/genética , ARN Mensajero/genética , Proteína 1A de Unión a Tacrolimus/genética , Factores de Transcripción/genéticaRESUMEN
Isolated non-compaction of the ventricular myocardium (INVM), sometimes referred to as 'spongy myocardium', is a congenital and exceedingly rare cardiomyopathy. Isolated ventricular non-compaction occurs in the absence of other structural heart diseases and, hypothetically, it is due to the arrest of myocardial morphogenesis. Isolated non-compaction of the ventricular myocardium may manifest itself from infancy to young adulthood with a high mortality rate. Both sexes are affected. In our study, we present a case of INVM (left and right ventricles) in a 3-year-old girl, diagnosed by two-dimensional echocardiography. The anomaly presented as a restrictive cardiomyopathy. The girl was admitted to our hospital with heart failure, when she was 10 months old. She was treated with dopamine, digoxin, furosemide, spironolactone, and acenocoumarol and her condition improved. Presently, the girl remains asymptomatic and for 3 years of follow-up, her development has been almost normal. We here describe the genetic background of this disorder (based on a literature review).
Asunto(s)
Cardiomiopatías/diagnóstico , Cardiomiopatías/genética , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/genética , Aciltransferasas , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/fisiopatología , Preescolar , Cromosomas Humanos/genética , Proteínas Asociadas a la Distrofina/genética , Femenino , Estudios de Seguimiento , Enfermedades Genéticas Congénitas/tratamiento farmacológico , Enfermedades Genéticas Congénitas/fisiopatología , Cardiopatías Congénitas/tratamiento farmacológico , Cardiopatías Congénitas/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Lactante , Intrones/genética , Lamina Tipo A/genética , Masculino , Mutación Missense , Proteínas/genética , Sitios de Empalme de ARN/genética , ARN Mensajero/genética , Proteína 1A de Unión a Tacrolimus/genética , Factores de Transcripción/genéticaRESUMEN
Mutations in SCN5A lead to a broad spectrum of phenotypes, including the Long QT syndrome, Brugada syndrome, Idiopathic ventricular fibrillation (IVF), Sudden infant death syndrome (SIDS) (probably regarded as a form of LQT3), Sudden unexplained nocturnal death syndrome (SUNDS) and isolated progressive cardiac conduction defect (PCCD) (Lev-Lenegre disease). Brugada Syndrome (BS) is a form of idiopathic ventricular fibrillation characterized by the right bundle-branch block pattern and ST elevation (STE) in the right precordial leads of the ECG. Mutations of the cardiac sodium channel SCN5A cause the disorder, and an implantable cardioverter-defibrillator is often recommended for affected individuals. In this study sequences of the coding region of the SCN5A gene were analysed in patients with the LQT3, Brugada Syndrome and other arrythmogenic disorders. Different mSSCP patterns are described with no disease-related SSCP conformers in any sample. Direct sequencing of the SCN5A gene confirmed the absence of mutations. This suggests that the analysed region of the SCN5A gene is not commonly involved in the pathogenesis of the Brugada Syndrome and associated disorders.