Abstract-Mutations in SCN5A, the gene encoding the cardiac Na ϩ channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT 3 ) and the Brugada syndrome. We have screened SCN5A in a large 8-generation kindred characterized by a high incidence of nocturnal sudden death, and QT-interval prolongation and the "Brugada ECG" occurring in the same subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the protein, was linked to the phenotype and was identified in all electrocardiographically affected family members. ECGs were obtained from 79 adults with a defined genetic status (carriers, nϭ43; noncarriers, nϭ36). In affected individuals, PR and QRS durations and QT intervals are prolonged (PϽ0.0001 for all parameters). ST segment elevation in the right precordial leads is present as well (PϽ0.0001). Twenty-five family members died suddenly, 16 of them during the night. Expression of wild-type and mutant Na ϩ channels in Xenopus oocytes revealed that the 1795insD mutation gives rise to a 7.3-mV negative shift of the steady-state inactivation curve and an 8.1-mV positive shift of the steady-state activation curve. The functional consequence of both shifts is likely to be a reduced Na ϩ current during the upstroke of the action potential. LQT 3 and Brugada syndrome are allelic disorders but may also share a common genotype. Key Words: long-QT syndrome Ⅲ Brugada syndrome Ⅲ SCN5A Ⅲ arrhythmia Ⅲ Na ϩ channel S CN5A, the gene that encodes the human cardiac Na ϩ channel ␣ subunit, 1 is mutated in one form of the long-QT syndrome (LQT 3 ) and in Brugada syndrome. 2,3 There are characteristic and readily distinguishable ECG patterns in these 2 syndromes. In LQT 3 patients, a long isoelectric ST segment precedes a peaked T wave. 4 Brugada syndrome is diagnosed on the basis of characteristic ECG features in the absence of structural heart disease; these features include right precordial ST-segment elevation, which may be intermittent, and which is exacerbated by Na ϩ channel block and ameliorated by isoproterenol. 5,6 QT intervals have been reported to be normal in patients with Brugada syndrome. 5 Clinically, there appears to be some overlap between the 2 syndromes, as both exhibit a relatively high incidence of nocturnal sudden cardiac death without prior symptoms. 6 -8 The prolonged QT interval in LQT 3 results from persistent inward Na ϩ current during the plateau phase of the action potential, secondary to incomplete inactivation of mutated channels. 9 Changes in the ␣ and ␤ 1 subunit interaction have also been implicated. 10 Although functional abnormalities have been described for Brugada syndrome-related SCN5A mutant channels, 3,11 the mechanism(s) whereby these explain the Brugada phenotype are less clear.In this study we present clinical and genetic data of a single large SCN5A-linked family, phenotypically characterized by nocturnal death and electrocardiograph...

Splenogonadal fusion is a rare congenital malformation in which there is an abnormal fusion between the spleen and the gonad or derivatives of the mesonephros. It can occur in both sexes but has been reported far more frequently in males. There are two types of this malformation: the continuous and the discontinuous type, depending on the presence or absence of a structural connection between the regular spleen and the ectopic splenic tissue that is fused to the gonad. In one-third of all reported cases splenogonadal fusion is associated with other congenital defects. This association is predominantly found within the continuous type. Peromelia is present in a high percentage of cases, varying from total absence of all limbs to absence of parts of the lower limbs. On the basis of a case report and a review of 84 published cases, the causal, pathogenetic and nosologic aspects of this malformation are discussed. We hypothesise that splenogonadal fusion with peromelia and splenogonadal fusion without peromelia represent two ends of one spectrum determined by the developmental stage during which the causal factor acts.

In order to understand the phenotypic spectrum of this rare disorder, cardiac evaluation should be made in patients with 3-methylcrotonyl-CoA carboxylase deficiency. Biochemical and clinical investigations have also to be performed in their parents and siblings. In addition, 3-methylcrotonyl-CoA carboxylase deficiency should be included in the differential diagnosis of dilatative cardiomyopathy.

At the age of 4 years, a total cavopulmonary connection was performed in a boy with a complex congenital heart defect. On addition, a DDDR pacemaker was implanted for sick sinus syndrome. Atrial and ventricular leads were epicardially placed at the left atrium and left ventricle. At the age of 10 years, a new epicardial ventricular lead was placed because of malfunction of the existing lead. At the same operation the pulse generator was replaced by a Medtronic Kappa DR 731. After replacement, the boy experienced episodes of phrenic nerve stimulation associated with feelings of discomfort. Holter recordings revealed ventricular stimulation from the atrial stimulus for 2 consecutive beats. This phenomenon repeated exactly every 3 hours and was caused by the automatic lead impedance measurement that used a 5-V, 1-ms stimulus output.

The role of antiarrhythmic drugs in the management of children with arrhythmias has changed due to the rapid development of radiofrequency ablation. Moreover, the release of new drugs and a better insight into the electrophysiologic mechanisms of arrhythmias have changed former patterns of drug management. However, because of lack of controlled trials, arrhythmia management in pediatrics is still mainly based on clinical studies and individual experience. Within these limitations, I attempt to give practical recommendations for the management of the different arrhythmias seen in children based on the latest developments in this area.