Biomedical subjects

J P van Tintelen

Publications and source records attributed to J P van Tintelen.

10 recordsLinked to original sources

PubMed2005

Can parents adjust to the idea that their child is at risk for a sudden death?: Psychological impact of risk for long QT syndrome.

Can a parent adjust to the idea that its child is at risk for a sudden death? This question is raised by a diagnostic procedure in which children were tested for an inherited Long QT Syndrome (LQTS). This potentially life-threatening but treatable cardiac arrhythmia syndrome may cause sudden death, especially in children and young adults. The long-term psychological effects are described for parents whose children were tested for inherited LQTS. The adverse short-term impact of such testing has been described previously. The goal of this investigation is to determine whether this distress endures. Thirty-six parents completed measures of psychological distress. With the twenty-four parents of carrier children, a semi-structured interview was held 18 months after DNA disclosure. Parents of carrier children reported more distress than parents of non-carrier children. Parents of carrier children remained vulnerable to high levels of distress; up to one-third of these parents showed clinically relevant high levels of distress. High levels of distress were reported by parents of carrier children who (1) were highly distressed at previous assessments, (2) were familiar with the disease for a longer time, (3) had experienced a sudden death in the family, (4) were lesser educated, and who (5) were unsatisfied with the given information. Parents were particularly concerned about possible hazardous behavior during puberty. We conclude that the continuous threat of developing LQTS symptoms despite prophylactic treatment affected the psychological well-being of the parents for a long time. In light of the tempetuous developments in the areas of cardiac genetics, periodical information on new insight and developments may act as a buffer for the parents' (growing) concerns about their child's inherited disorder.

Adolescent↗

PubMed2005

Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption.

Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a complex neuromigrational disorder including ependymal cysts, leptomeningeal and subcortical heterotopia, polymicrogyria, multifocal cerebral calcifications, agenesis of the corpus callosum, and spongiform changes in brainstem and cerebellum. Intractable lactic acidosis, causing death on the first day of life, was associated with severely reduced activities of complex I and complex IV. The neuropathological and biochemical findings are closely similar to those reported previously. The findings confirm a distinct genetic syndrome of disrupted brain development with TORCH-like calcifications, and a complex neuronal migration disorder associated with a multicomplex disorder of the respiratory chain.

Acidosis, Lactic↗

PubMed2005

High distress in parents whose children undergo predictive testing for long QT syndrome.

OBJECTIVES: To assess the psychological effect of predictive testing in parents of children at risk for long QT syndrome (LQTS) in a prospective study. METHODS: After their child was clinically screened by electrocardiography and blood was taken for DNA analysis, and shortly after delivery of the DNA test result, 36 parents completed measures of psychological distress. RESULTS: 24 parents were informed that at least one of their children is a mutation carrier. Up to 50% of the parents of carrier children showed clinically relevant high levels of distress. Parents who were familiar with the disease for a longer time, who had more experiences with the disease in their family and who received positive test results for all their children were most distressed. CONCLUSIONS: Predictive ECG testing together with DNA testing has a profound impact on parents whose minors undergo predictive testing for LQTS.

Adolescent↗

PubMed2004

[Arrhythmogenic right-ventricular cardiomyopathy: different manifestations as precursors of sudden death which might be prevented].

Two men aged 47 and 56 and one woman aged 21 presented at our cardiology department with presyncope, heart failure and exercise induced palpitations, respectively. Using the criteria of McKenna et al., a diagnosis of arrhythmogenic right-ventricular cardiomyopathy (ARVC) was made. Following implantation of a defibrillator, one of the men experienced seven appropriate interventions within six months and also developed psychological problems. The other man was problem-free and the woman recovered reasonably well, having only one appropriate intervention from the defibrillator one year after implantation. Indications of ARVC were also found in her mother but not in any other family members. Because ARVC manifests itself in various different ways it is difficult to diagnose. It is important to consider ARVC in patients with exercise-induced palpitations, presyncope, and unexplained cardiomyopathies or arrhythmias, especially if there is a family history of unexpected deaths. ARVC is a potentially life-threatening disease, that may require implantation of a cardioverter defibrillator. Furthermore, since genetics play an important role and ARVC can be asymptomatic, evaluation of close relatives for preclinical symptoms is important.

Adult↗

PubMed2004

[Implantable cardioverter-defibrillator in the treatment of two patients with an increased risk of sudden cardiac death].

A 23-year-old female with familial long-QT syndrome and a 48-year-old male with familial dilated cardiomyopathy were given an implantable cardioverter-defibrillator (ICD) as prophylaxis. About half a year after the implantation, there was an appropriate and successful ICD-discharge in both patients in connection with ventricular tachycardia. Treatment with an ICD can be life-saving in patients with cardiac rhythm disorders. The most common indication is ventricular tachycardia or fibrillation due to ischaemic heart disease, but an ICD may also be indicated in patients with cardiomyopathy, congenital heart disease, hereditary arrhythmia or a planned heart transplantation.

Adult↗

PubMed2000

Bohring syndrome.

Explore the source record for details and available documents.

Abnormalities, Multiple↗

PubMed2000

[Long QT-interval syndrome and investigation of heritability: psychological reactions in three generations in one family].

DNA diagnostics were carried out in a family after the long QT interval syndrome had been diagnosed in one of its members. The psychic reactions to this testing were different from those seen in other hereditary diseases such as Huntington's disease. This was probably due to the sudden and unexpected occurrence of the arrhythmia. The family members in whom clinical and DNA diagnostics gave purely negative findings were not relieved, owing to solidarity with the affected relatives. Their partners did not understand this response. The anxiety and concern of the gene carriers had nothing to do with their own health status but with that of their carrier children. These parents were in need of educational counselling and advice. The results of clinical and DNA diagnostics affected the family relationships: in carriers the feeling of closeness grew, while the non-carriers were afraid of loss of family closeness.

Adult↗

PubMed1999

[Presymptomatic screening after a sudden cardiac death in the family].

Sudden cardiac death without ischaemic heart disease may be due to a hereditary heart disease with an autosomal dominant heredity. The occurrence, if any, of sudden death in such a family is a main indicator for the risk of sudden cardiac death in other family members. Cardiological and/or genetic investigation may reveal a hereditary disease in relatives without symptoms. Of some of these pathological conditions, the corresponding chromosomal localizations and sometimes the gene mutations have been identified. The psychic burden of family investigation and the socio-economic consequences (insurances, occupation, family relationships) are potentially heavy. Prophylactic treatment of asymptomatic persons in whom a gene mutation is established may comprise advice about lifestyle (e.g. avoidance of peak exercise in patients with hypertrophic cardiomyopathy), medication (e.g. beta-receptor blockers in patients with a long QT interval) or implantation of a pacemaker or internal defibrillator (e.g. in asymptomatic persons with the Brugada syndrome, a form of right bundle branch block). Presymptomatic investigation must be performed multidisciplinary.

Cardiovascular Diseases↗

PubMed1999

Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.

Congenital long QT syndrome (cLQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncopes, seizure, or sudden death. LQTS can occur either as an autosomal dominant (Romano Ward) or as an autosomal recessive disorder (Jervell and Lange-Nielsen syndrome). Mutations in at least five genes have been associated with the LQTS. Four genes, encoding cardiac ion channels, have been identified. The most common forms of LQTS are due to mutations in the potassium-channel genes KCNQ1 and HERG. We have screened 24 Dutch LQTS families for mutations in KCNQ1 and HERG. Fourteen missense mutations were identified. Eight of these missense mutations were novel: three in KCNQ1 and five in HERG. Novel missense mutations in KCNQ1 were Y184S, S373P, and W392R and novel missense mutations in HERG were A558P, R582C, G604S, T613M, and F640L. The KCNQ1 mutation G189R and the HERG mutation R582C were detected in two families. The pathogenicity of the mutations was based on segregation in families, absence in control individuals, the nature of the amino acid substitution, and localization in the protein. Genotype-phenotype studies indicated that auditory stimuli as trigger of cardiac events differentiate LQTS2 and LQTS1. In LQTS1, exercise was the predominant trigger. In addition, a number of asymptomatic gene defect carriers were identified. Asymptomatic carriers are still at risk of the development of life-threatening arrhythmias, underlining the importance of DNA analyses for unequivocal diagnosis of patients with LQTS.

Cation Transport Proteins↗

PubMed1999

Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1).

OBJECTIVE: This study was performed to identify a possible relationship between genotype and phenotype in the congenital familial long QT syndrome (cLQTS). BACKGROUND: The cLQTS, which occurs as an autosomal dominant or recessive trait, is characterized by QT-interval prolongation on the electrocardiogram and torsade de pointes arrhythmias, which may give rise to recurrent syncope or sudden cardiac death. Precipitators for cardiac events are exercise or emotion and occasionally acoustic stimuli. METHODS: The trigger for cardiac events (syncope, documented cardiac arrhythmias, sudden cardiac death) was analyzed in 11 families with a familial LQTS and a determined genotype. RESULTS: The families were subdivided in KVLQT1-related families (LQTS1, n = 5) and HERG (human ether-a-gogo-related gene)-related families (LQTS2, n = 6) based on single-strand conformation polymorphism analysis and sequencing. Whereas exercise-related cardiac events dominate the clinical picture of LQTS1 patients, auditory stimuli as a trigger for arrhythmic events were only seen in LQTS2 patients. CONCLUSIONS: Arrhythmic events triggered by auditory stimuli may differentiate LQTS2 from LQTS1 patients.

Acoustic Stimulation↗