Coexistence of Andersen-Tawil Syndrome with Polymorphisms in hERG1 Gene (K897T) and SCN5A Gene (H558R) in One Family.

BACKGROUND: Andersen-Tawil Syndrome (ATS) is a channelopathy caused by mutations in KCNJ2 gene. It is characterized by symptoms of ventricular arrhythmias, periodic paralysis or muscle weakness, and dysmorphic features. ATS can present with the triad of symptoms, any combination or none of them. Risk factors for dangerous arrhythmias are unknown. The study assessed the impact of K897T polymorphism in hERG1 gene and H558R polymorphism in SCN5A gene coexisting with R218Q mutation in KCNJ2 in one family on clinical manifestation. METHODS: Family members underwent clinical assessment, ECG and genotyping. Holter monitoring was performed in mutation carriers and additionally in one family member with no mutation, but with K897T polymorphism. RESULTS: Proband with ATS mutation, K897T and H558R polymorphisms and proband's sister with ATS mutation and K897T polymorphism presented following symptoms: loss of consciousness, bidirectional and polymorphic ventricular tachycardia and about 5000 ventricular extrasystoles. Symptoms presented by the member with only the ATS mutation and by member with ATS mutation and H558R polymorphism were not as severe. U wave appeared in all examined family members regardless of the mutation presence. Studied individuals with ATS mutation had the T-peak-U-peak interval longer than 200 ms. In all ATS mutation carriers it was longer than in family members with no mutation. T-peak-T-end interval was the longest (>120 ms) in members with coexisting mutation and K897T polymorphism. CONCLUSION: ATS severity possibly depends on other genes' polymorphisms. In the presented family, it could depend on the presence of K897T polymorphism in hERG1.

"Migraine side effect" and stroke recurrence in late follow-up after transcatheter patent foramen ovale closure as secondary prevention of cryptogenic thromboembolism.

INTRODUCTION: Patent foramen ovale (PFO) is associated with cryptogenic strokes, recurrent transient neurologic deficits, sleep apnea, decompression illness and migraines with aura. AIM: We verify cryptogenic embolism recurrence after transcatheter PFO closure in patients younger than 55 years old, and determine the prevalence of migraine with aura before and after PFO closure. MATERIAL AND METHODS: We sent a questionnaire concerning the recurrence of stroke or transient ischemic attack (TIA) and the presence of migraine symptoms before and after PFO closure to 224 consecutive patients (mean age 40.9 ±9 years; 103 men; 108 patients < 40 years old, 116 patients 40-55 years old) after successful PFO transcatheter closure as secondary prevention of cryptogenic embolism. RESULTS: The mean follow-up period was 37.8 ±32.5 (median 27) months. Stroke or TIA recurred in 6 patients (2.6%), all of whom were over 40 years old at the time of closure. The median time of recurrence was 24 months. Two patients (0.89%) died, but the deaths were not related to the device nor to thromboembolism. Migraine occurred in the study group before closure in 68 (30.4%) patients. After the procedure 55 (80.9%) reported improvement or disappearance of migraine symptoms. CONCLUSIONS: Recurrent strokes after PFO closure are rare, and they occur more often in patients over 40 years old at the time of closure. The PFO closure results in migraine subsiding or symptoms noticeably ameliorating.

Electrocardiogram in Andersen-Tawil syndrome. New electrocardiographic criteria for diagnosis of type-1 Andersen-Tawil syndrome.

Andersen - Tawil syndrome (ATS) is an autosomal - dominant or sporadic disorder characterized by ventricular arrhythmias, periodic paralysis, and distinctive facial and skeletal dysmorphism. Mutations in KCNJ2, which encodes the α-subunit of the potassium channel Kir2.1, were identified in patients with ATS. This genotype has been designated as type-1 ATS (ATS1). KCNJ2 mutations are detectable in up to 60 % of patients with ATS. Cardiac manifestations of ATS include frequent premature ventricular contractions (PVC), Q-U interval prolongation, prominent U-waves, and a special type of polymorphic ventricular tachycardia (PMVT) called bidirectional ventricular tachycardia (BiVT). The presence of frequent PVCs at rest are helpful in distinguishing ATS from typical catecholaminergic polymorphic ventricular tachycardia (CPVT). In typical CPVT, rapid PMVT and BiVT usually manifest during or after exercising. Additionally, CPVT or torsade de pointes in LQTS are faster, very symptomatic causing syncope or often deteriorate into VF resulting in sudden cardiac death. PVCs at rest are quite frequent in ATS1 patients, however, in LQTS patients, PVCs and asymptomatic VT are uncommon which also contributes to differentiating them. The article describes the new electrocardiographic criteria proposed for diagnosis of type-1 Andersen-Tawil syndrome. A differential diagnosis between Andersen-Tawil syndrome, the catecholamine polymorphic ventiruclar tachycardia and long QT syndrome is depicted. Special attention is paid on the repolarization abnormalities, QT interval and the pathologic U wave. In this article, we aim to provide five new electrocardiographic clues for the diagnosis of ATS1.