Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the long QT syndrome (LQT), individuals suffer from syncope, seizures and sudden death due to cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. Many of these individuals also have prolongation of the QT interval on electrocardiograms, suggesting abnormal cardiac repolarization. To improve our understanding of the mechanisms underlying LQT and to facilitate presymptomatic diagnosis, we have begun to study families with autosomal dominant LQT. In 1991, we reported tight linkage between the LQT phenotype and the Harvey ras-1 gene (HRAS) in several families of Northern European descent. This discovery localized an LQT gene to chromosome 11p15.5 and made presymptomatic diagnosis in some families possible. In initial experiments, no recombination between HRAS and LQT was observed, making this protoncogene a candidate for LQT. This hypothesis was supported by physiologic data; other investigators had shown that ras proteins modulate cardiac potassium channels and an abnormality of potassium homeostasis could explain LQT. We eliminated HRAS as a candidate, however, by sequencing the coding region in 10 unrelated patients and finding no mutations. This indicated that the LQT locus was nearby, but not HRAS. Autosomal dominant LQT was previously thought to be genetically homogeneous and the first seven LQT families we studied were linked to 11p15.5. In 1992, however, several groups, including my laboratory, identified locus heterogeneity for LQT. Recently we identified a second LQT locus, LQT2, on chromosome 7q35-36. Because several families were unlinked, at least one more LQT locus exists. This degree of heterogeneity presents opportunities. It seems likely, for example, that proteins encoded by distinct LQT genes interact to modulate cardiac repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular genetics of long QT syndrome. 767 24

Long QT syndrome (LQTS), is an inherited cardiac disorder in which ventricular tachyarrhythmias predispose affected individuals to syncope, seizures, and sudden death. Characteristic electrocardiographic findings include a prolonged QT interval, T wave alternans, and notched T waves. We have screened LQTS patients from 89 families for mutations in the pore region of HERG , the K+ channel gene previously associated with chromosome 7-linked LQT2. In six unrelated LQTS kindreds, single-strand conformation polymorphism analyses identified aberrant conformers in all affected family members. These conformers were not seen in over 100 unaffected, unrelated control individuals, suggesting that they represent pathogenic LQTS mutations. DNA sequence analyses of the aberrant conformers demonstrated that they reflect five different missense mutations: V612L, A614V, N629D, N629S, and N633S. The missense mutation A614V was found in two unrelated families. Further functional studies will be required to determine what effect each of these changes may have on HERG channel function.
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PMID:Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome. 954 37

Congenital long QT syndrome (LQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). As a result of these arrhythmias, patients suffer from recurrent syncopes, seizures, or sudden death as the most dramatic event. Mutations in five genes, encoding cardiac ion channels, have been identified in LQTS. Two potassium-channel genes, KCNQ1 (LQT1) and KCNH2 (LQT2 or HERG), are frequently involved in LQTS. Potassium-channel defects account for approximately 50-60% of LQTS. As patients benefit from preventive medication, early detection of a genetic defect is desired to identify the family members at risk. Speed and sensitivity of mutation detection was improved by applying the denaturing high performance liquid chromatography (DHPLC) technique for analysis of the entire KCNQ1 and KCNH2 genes and the protein encoding part of the KCNE1 and KCNE2 genes. By using this methodology, seven missense mutations in the KCNQ1 gene and nine mutations (four missense, two nonsense, one insertion, and two deletions) in the KCNH2 gene have been identified in a total number of 32 index patients diagnosed with LQTS syndrome. We conclude that this method is suitable for rapid identification of LQT gene defects due to the combination of automation, high throughput, sensitivity, and short time of analysis.
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PMID:DHPLC analysis of potassium ion channel genes in congenital long QT syndrome. 1240 36

An 18-year old female taking anti-epileptic medication was found unconscious in her bed early in the morning. After documented ventricular fibrillation and successful resuscitation, the patient was admitted to our emergency care unit. According to ECG criteria a long-QT syndrome of the subtype 2 was suspected. A few days later, however, the patient died because of hypoxic brain death. From previous hospital reports it turned out that the patient had repeatedly experienced syncopes in the past, which were interpreted as epileptic seizures. Her 17-year old sister and the female twin of her mother had both recently died from sudden cardiac death of unknown cause. An ECG screening in the family revealed six members with LQTS. A genetic analysis revealed in all of them a previously not described rearrangement mutation (888 delG insAA) in the LQT2 gene ( HERG) that was predicted to cause a protein truncation (360X) in the amino acid chain of the I(Kr)-channel subunit. This casuistic contribution exemplifies some classical aspects of LQTS (typical adrenergic trigger mechanism, classical false diagnosis "epilepsy") and demonstrates the possibility of a genotypic classification guided by phenotypic ECG characteristics. It represents an unusual case of a LQTS with a high degree of malignancy, which requires aggressive therapeutic interventions for the family survivors.
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PMID:[18-year old patient with anti-epileptic therapy and sudden cardiac death]. 1508 78

A 60-year-old man with a long history of epilepsy was referred for cardiologic evaluation. An earlier diagnosis of epilepsy was made on the basis of his clinical manifestation of tonic-clonic seizure. Electroencephalography (EEG) demonstrated paroxysmal slow waves in response to intermittent photic stimulation. However, electrocardiography (ECG) revealed bradycardia (heart rate, 48 bpm) and marked QT prolongation (QTc 477 ms). ECG monitoring confirmed remarkable QT prolongation; ventricular ectopy triggering torsades de pointes was recorded during seizure. The patient underwent temporary antitachycardia pacing, and an implantable cardioverter defibrillator (ICD) was finally implanted. Long QT syndrome (LQTS) genetic testing was conducted and a diagnosis of LQT2 was confirmed by the identification of mutation in KCNH2 (HERG). LQTS is associated with abnormal channel function due to mutations in ion channel genes. Epilepsy, a disorder of neural function, is also associated with abnormal channel function. The possibility that some channelopathies can manifest as both LQTS and epilepsy is discussed.
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PMID:Congenital long QT syndrome presenting with a history of epilepsy: misdiagnosis or relationship between channelopathies of the heart and brain? 1969 97

We report a 13-year-old girl with congenital long QT syndrome (LQTS) who developed a cluster of generalized tonic clonic seizures with post-ictal EEG abnormality. The provisional diagnosis was epilepsy. However, ECG monitoring showed torsade de pointes, and thus the final diagnosis was LQTS. Although LQTS can be potentially misdiagnosed as epilepsy when it presents with seizures, it is important to differentiate LQTS from epilepsy because patients with LQTS are at risk of sudden death. We reviewed 11 previously reported cases with LQTS and EEG abnormalities who were initially diagnosed as epilepsy. We emphasized the importance of the following five criteria in the differentiation of LQTS from epilepsy: 1) awareness that LQT2 and LQT3 can cause life-threatening arrhythmia at rest or during sleep, 2) examination of arterial pulse during seizures, 3) monitoring ECG during EEG recording, 4) careful establishment of the correct diagnosis taking into consideration the interictal EEG findings, and 5) reconsidering the possibility of cardiac origin when the attacks cannot be controlled even by therapeutic levels of antiepileptic drugs in the blood.
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PMID:[Criteria for differential diagnosis of epilepsy and long QT syndrome presenting with seizures and EEG abnormalities]. 1992 43