Different responses to exercise between Andersen–Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia

Inoue, Yuko; Aiba, Takeshi; Kawata, Hiro; Sakaguchi, Tomoko; Mitsuma, Wataru; Morita, Hiroshi; Noda, Takashi; Takaki, Hiroshi; Toyohara, Keiko; Kanaya, Yoshiaki; Itoi, Toshiyuki; Mitsuhashi, Takeshi; Sumitomo, Naokata; Cho, Yongkeun; Yasuda, Satoshi; Kamakura, Shiro; Kusano, Kengo; Miyamoto, Yoshihiro; Horie, Minoru; Shimizu, Wataru

doi:10.1093/europace/eux351

Cited by 19 publications

(24 citation statements)

References 21 publications

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“…Noticeably, the ECG during exercise testing is also different for both groups: ventricular arrhythmias appear early, stop at the peak of exercise to finally reappear after the end of exercise for KCNJ2 -mutated patients with CPVT, while in other CPVT patients they appear early, increase to reach the maximum at peak and stop at rest. The morphology of PVC is different between the two groups: right BBB pattern is more frequent in KCNJ2 -mutated patients with CPVT whereas left BBB pattern if more associated with mutations in other genes ( Inoue et al, 2018 ). Interestingly, proband 2 of our study presented a Pierre Robin sequence.…”

Section: Discussionmentioning

confidence: 98%

“…KCNJ2 -mutated patients with CPVT are all females ( Andelfinger et al, 2002 ; Tester et al, 2006 ; Kukla et al, 2014 ), for whom the age of onset or diagnosis ranges from 2 to 36, with a mean around 15, as compared to 8 years old for RYR2 -related CPVT ( Ackerman et al, 2011 ). In addition, VA reported in patients with KCNJ2 mutations have been described as milder than in RYR2 mutated patient, especially rarely leading to syncope or sudden cardiac arrest ( Andelfinger et al, 2002 ; Tristani-Firouzi et al, 2002 ; Delannoy et al, 2013 ; Kukla et al, 2014 ; Inoue et al, 2018 ). Reported KCNJ2 -mutated patients with CPVT consistently show an abnormal resting ECG, while only exercise stress test triggers detectable ECG signs for other CPVT patients.…”

Section: Discussionmentioning

confidence: 99%

“…Reported KCNJ2 -mutated patients with CPVT consistently show an abnormal resting ECG, while only exercise stress test triggers detectable ECG signs for other CPVT patients. The resting ECG in KCNJ2 -mutated patients may present characteristic T-U wave patterns comprising biphasic and enlarged U-waves increasing in amplitude during tachycardia, prolonged terminal T downslope, wide T-U junctions, fusion of T and U waves after PVC, and U on P sign during sinus tachycardia ( Zhang et al, 2005 ; Kukla et al, 2014 ; Inoue et al, 2018 ). Due to these features, QT can appear prolonged explaining why KCNJ2 -mutated patients had long been misdiagnosed with LQTS, and ATS considered as a syndromic form of LQTS (named LQT7).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome

Tanno

Folacci²,

Révilloud³

et al. 2021

Front. Genet.

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Andersen-Tawil Syndrome (ATS) is a rare disease defined by the association of cardiac arrhythmias, periodic paralysis and dysmorphic features, and is caused by KCNJ2 loss-of-function mutations. However, when extracardiac symptoms are atypical or absent, the patient can be diagnosed with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a rare arrhythmia at high risk of sudden death, mostly due to RYR2 mutations. The identification of KCNJ2 variants in CPVT suspicion is very rare but important because beta blockers, the cornerstone of CPVT therapy, could be less efficient. We report here the cases of two patients addressed for CPVT-like phenotypes. Genetic investigations led to the identification of p. Arg82Trp and p. Pro186Gln de novo variants in the KCNJ2 gene. Functional studies showed that both variants forms of Kir2.1 monomers act as dominant negative and drastically reduced the activity of the tetrameric channel. We characterize here a new pathogenic variant (p.Pro186Gln) of KCNJ2 gene and highlight the interest of accurate cardiologic evaluation and of attention to extracardiac signs to distinguish CPVT from atypical ATS, and guide therapeutic decisions. We also confirm that the KCNJ2 gene must be investigated during CPVT molecular analysis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome

Tanno

Folacci²,

Révilloud³

et al. 2021

Front. Genet.

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“…In a case-control study of 26 ATS patients, Inoue et al found increased ventricular arrhythmias with increasing heart rate in 35% of cases. The arrhythmias C o r r e c t e d P r o o f disappeared as the heart rate approached its maximum but increased again in the recovery phase [28].…”

Section: Anderson-tawil Syndromementioning

confidence: 97%

The Role of Nutrition and Physical Activity as Trigger Factors of Paralytic Attacks in Primary Periodic Paralysis

Welland¹,

Hæstad

Fossmo

et al. 2021

JND

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Background: Primary periodic paralysis (PPP) are rare inherited neuromuscular disorders including Hypokalemic periodic paralysis (HypoPP), Hyperkalemic periodic paralysis (HyperPP) and Andersen-Tawil syndrome (ATS) characterised by attacks of weakness or paralysis of skeletal muscles. Limited effective pharmacological treatments are available, and avoidance of lifestyle related triggers seems important. Objective: Our aim was to search and assess the scientific literature for information on trigger factors related to nutrition and physical activity in PPP. Methods: We searched Ovid Medline and Embase database for scientific papers published between January 1, 1990, to January 31, 2020. Results: We did not identify published observation or intervention studies evaluating effect of lifestyle changes on attacks. Current knowledge is based on case-reports, expert opinions, and retrospective case studies with inadequate methods for description of nutrition and physical activity. In HypoPP, high carbohydrate and salt intake, over-eating, alcohol, dehydration, hard physical activity, and rest after exercise are frequently reported triggers. Regarding HyperPP, fasting, intake of potassium, alcohol, cold foods or beverages, physical activity, and rest after exercise are frequently reported triggers. No nutrition related triggers are reported regarding ATS, exercise can however induce ventricular arrhythmias. Conclusions: Our results support that dietary intake and physical activity may play a role in causing paralytic attacks in PPP, although the current scientific evidence is weak. To provide good evidence-based patient care, several lifestyle aspects need to be further assessed and described.

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“…Due to the recent discovery of TRDN 47 , CALM1 44 , and TECRL 55 genes as causes of CPVT, their inclusion in previous guidelines had not been contemplated, but we recommend screening after exclusion of RYR2 and CASQ as causes of this disease. Other genes to consider in a genetic test are KCNJ2 [71][72][73][74] and ANKB 75 .…”

Section: Genetic Testingmentioning

confidence: 99%

Basic and Clinical Insights in Catecholaminergic (Familial) Polymorphic Ventricular Tachycardia

Márquez¹,

Totomoch-Serra²,

Rueda³

et al. 2019

RIC

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

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Different responses to exercise between Andersen–Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia

Cited by 19 publications

References 21 publications

Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome

Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome

The Role of Nutrition and Physical Activity as Trigger Factors of Paralytic Attacks in Primary Periodic Paralysis

Basic and Clinical Insights in Catecholaminergic (Familial) Polymorphic Ventricular Tachycardia

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