Andersen syndrome autosomal dominant in three generations

Canún, Sonia; Pérez, Nohemí; Beirana, Luisa G.

doi:10.1002/(sici)1096-8628(19990716)85:2<147::aid-ajmg9>3.0.co;2-0

Cited by 62 publications

(33 citation statements)

References 7 publications

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“…Furthermore, our large cohort of ATS1 subjects demonstrated other fundamental ECG and clinical differences between ATS1 and LQTS. In ATS1, patients generally seek medical attention because of periodic paralysis [1][2][3][4]7,8,11 rather than because of the ventricular arrhythmia, consisting of frequent PVCs, mainly in bigeminy, and nonsustained polymorphic, often bidirectional, VT (Tables 1 and 2 and Figure 2), which are usually asymptomatic. Cardiac conduction abnormalities, infrequently seen in LQTS patients, were observed in 23% of ATS1 patients.…”

Section: Discussionmentioning

confidence: 99%

Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations

et al. 2005

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Background-The ECG features of Andersen-Tawil syndrome (ATS) patients with KCNJ2 mutations (ATS1) have not been systematically assessed. This study aimed to define ECG features of KCNJ2 mutation carriers, to determine whether characteristic T-U-wave patterns exist, and to establish whether T-U patterns predict the ATS1 genotype. Methods and Results-In phase I, evaluation of T-U morphology in ECGs of 39 KCNJ2 mutation carriers identified characteristic T-U patterns: prolonged terminal T downslope, wide T-U junction, and biphasic and enlarged U waves. In phase II, ATS1 genotype prediction by T-U pattern was evaluated in the next 147 ECGs (57 other KCNJ2 mutation carriers, 61 unaffected family members, and 29 ATS patients without KCNJ2 mutations), with a sensitivity of 84% and specificity of 97%. Characteristic T-U patterns were present in 91% (87/96), in whom an enlarged U wave was predominant (73%). In phase III, QTc, QUc, and T-and U-wave duration/amplitude were compared in the 96 ATS1, 29 non-KCNJ2 ATS, and 75 normal subjects. In ATS1 patients, QUc, U-wave duration and amplitude, and QTc were all increased (PϽ0.001), but median QTc and interquartile range (IQR) were just 440 ms (IQR, 28 ms) compared with 420 ms (IQR, 20 ms) in normal subjects and 425 ms (IQR, 48 ms) in ATS non-KCNJ2 patients. Conclusions-In ATS1 patients, gene-specific T-U-wave patterns resulting from decreased I K1 owing to KCNJ2 mutations can aid diagnosis and direct genotyping. The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7. (Circulation. 2005;111:2720-2726.)

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Section: Discussionmentioning

confidence: 99%

Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations

et al. 2005

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“…The characteristic facial and skeletal abnormalities are often a diagnostic clue to ATS, although they may be subtle. [1][2][3][4] Clinical heterogeneity is remarkable in this syndrome: electrocardiographic (ECG) abnormalities may be the only manifestation of an affected individual within a family with otherwise typical ATS. Recently, ATS has been linked to mutations in the KCNJ2 gene which codes for a voltagegated, inward rectifying potassium channel (Kir2.1).…”

Section: Introductionmentioning

confidence: 99%

Management and Treatment of Andersen-Tawil Syndrome (ATS)

Sansone

Tawil

2007

Neurotherapeutics

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Summary: Andersen-Tawil syndrome (ATS) is characterized by periodic paralysis, cardiac arrhythmias, and distinct facial and skeletal features. The majority of patients with ATS (ATS1) have point mutations in the KCNJ2 gene, which encodes the inward-rectifying potassium channel known as Kir2.1. The skeletal muscle and cardiac symptoms are accounted for, in most cases, by a dominant negative effect of the mutations on potassium channel current, resulting in prolonged depolarization of the action potential. Mechanisms of disruption of channel function include abnormal trafficking and assembly of second messengers such as phosphatidylinositol 4,5-bisphosphate, abnormal gating of the channel, and incorrect folding of the Kir2.1 protein. Less apparent is the mechanism by which these mutations account for the typical facial and skeletal abnormalities. The concomitant involvement of cardiac and skeletal muscle in ATS poses unique treatment and management challenges. Because of differences in cardiac and skeletal muscle physiology, drugs that may have a beneficial effect on cardiac function may have a detrimental effect on skeletal muscle and vice versa. We review the clinical, laboratory, and genetic features of this disorder with particular emphasis on treatment and management.

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“…Andersen-Tawil syndrome (ATS, MIM# 170390) is a rare autosomal dominant disorder characterized by classical triad: (1) ventricular tachyarrythmias associated with QT prolongation in electrocardiograms (ECGs), (2) periodic paralysis, and (3) dysmorphic features (Andersen, et al, 1971;Canun, et al, 1999;Sansone, et al, 1997;Tawil, et al, 1994). Plaster et al revealed that mutations in KCNJ2 (MIM# 600681) caused the syndrome in the majority of clinically diagnosed ATS families (Plaster, et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Genotype-phenotype correlations ofKCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome

et al. 2007

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Andersen-Tawil syndrome (ATS) is a rare inherited disorder characterized by periodic paralysis, mild dysmorphic features, and QT or QU prolongation with ventricular arrhythmias in electrocardiograms (ECGs Functional assays for the two novel KCNJ2 mutations (c. 200G>A (p. R67Q) and c. 436G>A (p. G146S)) displayed no functional inward rectifying currents in a heterologous expression system and showed strong dominant negative effects when co-expressed with wild-type KCNJ2 channels (91% and 84% reduction at -50 mV respectively compared to wild-type alone). Immunocytochemistry and confocal imaging revealed normal trafficking for mutant channels. In our study, all of the clinically diagnosed ATS patients had KCNJ2 mutations and showed a high penetrance with regard to the typical cardiac phenotypes: predominant U wave and ventricular arrhythmias, typically bidirectional VT.

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Andersen syndrome autosomal dominant in three generations

Cited by 62 publications

References 7 publications

Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations

Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations

Management and Treatment of Andersen-Tawil Syndrome (ATS)

Genotype-phenotype correlations ofKCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome

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