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Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome(VACRDS)

MedGen UID:
1781114
•Concept ID:
C5542154
•
Disease or Syndrome
Synonym: Autosomal dominant cardiac arrhythmia (Kuhn)
 
Gene (location): RYR2 (1q43)
 
Monarch Initiative: MONDO:0020745
OMIM®: 115000

Definition

Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome (VACRDS) is characterized by syncope, cardiac arrest, and/or sudden unexpected death. Polymorphic ventricular tachycardia and ventricular fibrillation have been documented in these patients. Symptoms generally occur with physical activity or emotional stress, but unlike typical catecholaminergic ventricular tachycardia (CPVT), arrhythmias are not reproducible on exercise stress testing or adrenaline challenge (Sun et al., 2021). Mutation in the RYR2 gene also causes catecholaminergic polymorphic ventricular tachycardia-1 (CPVT1; 604772). [from OMIM]

Clinical features

From HPO
Sudden cardiac death
MedGen UID:
38841
•Concept ID:
C0085298
•
Pathologic Function
The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).
See: Feature record | Search on this feature
Torsades de pointes
MedGen UID:
21214
•Concept ID:
C0040479
•
Disease or Syndrome
A type of ventricular tachycardia characterized by polymorphioc QRS complexes that change in amplitue and cycle length, and thus have the appearance of oscillating around the baseline in the EKG.
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Ventricular fibrillation
MedGen UID:
21844
•Concept ID:
C0042510
•
Disease or Syndrome
Uncontrolled contractions of muscles fibers in the left ventricle not producing contraction of the left ventricle. Ventricular fibrillation usually begins with a ventricular premature contraction and a short run of rapid ventricular tachycardia degenerating into uncoordinating ventricular fibrillations.
See: Feature record | Search on this feature
Left ventricular noncompaction cardiomyopathy
MedGen UID:
866782
•Concept ID:
C4021133
•
Disease or Syndrome
Left ventricular non-compaction (LVNC) is characterized by prominent left ventricular trabeculae and deep inter-trabecular recesses. The myocardial wall is often thickened with a thin, compacted epicardial layer and a thickened endocardial layer. In some patients, LVNC is associated with left ventricular dilatation and systolic dysfunction, which can be transient in neonates.
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Polymorphic and polytopic ventricular extrasystoles
MedGen UID:
870550
•Concept ID:
C4024998
•
Disease or Syndrome
See: Feature record | Search on this feature
Aborted sudden cardiac death
MedGen UID:
1632505
•Concept ID:
C4703449
•
Finding
Cardiac arrest that would have led to rapid and unexpected death had an intervention not taken place to prevent it.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor.
Przybylski R, Abrams DJ
Curr Opin Cardiol 2023 Jul 1;38(4):390-395. Epub 2023 Mar 28 doi: 10.1097/HCO.0000000000001051. PMID: 37016946

Recent clinical studies

Etiology

Diverse Phenotypic Manifestations in a Family with a Novel RYR2 E4107A Variant.
Hasegawa H, Tamura S, Nakajima T, Kawabata-Iwakawa R, Kobari T, Matsumoto N, Sano Y, Nishiyama M, Kurabayashi M, Kaneko Y, Nakatani Y, Ishii H
Int Heart J 2024;65(3):580-585. doi: 10.1536/ihj.23-652. PMID: 38825499
Therapeutic Approaches of Ryanodine Receptor-Associated Heart Diseases.
Szentandrássy N, Magyar ZÉ, Hevesi J, Bányász T, Nánási PP, Almássy J
Int J Mol Sci 2022 Apr 18;23(8) doi: 10.3390/ijms23084435. PMID: 35457253Free PMC Article
Provocation Testing and Therapeutic Response in a Newly Described Channelopathy: RyR2 Calcium Release Deficiency Syndrome.
Ormerod JOM, Ormondroyd E, Li Y, Taylor J, Wei J, Guo W, Wang R, Sarton CNS, McGuire K, Dreau HMP, Taylor JC, Ginks MR, Rajappan K, Chen SRW, Watkins H
Circ Genom Precis Med 2022 Feb;15(1):e003589. Epub 2021 Dec 24 doi: 10.1161/CIRCGEN.121.003589. PMID: 34949103
Clinical and Functional Characterization of Ryanodine Receptor 2 Variants Implicated in Calcium-Release Deficiency Syndrome.
Roston TM, Wei J, Guo W, Li Y, Zhong X, Wang R, Estillore JP, Peltenburg PJ, Noguer FRI, Till J, Eckhardt LL, Orland KM, Hamilton R, LaPage MJ, Krahn AD, Tadros R, Vinocur JM, Kallas D, Franciosi S, Roberts JD, Wilde AAM, Jensen HK, Sanatani S, Chen SRW
JAMA Cardiol 2022 Jan 1;7(1):84-92. doi: 10.1001/jamacardio.2021.4458. PMID: 34730774Free PMC Article
Identification of loss-of-function RyR2 mutations associated with idiopathic ventricular fibrillation and sudden death.
Zhong X, Guo W, Wei J, Tang Y, Liu Y, Zhang JZ, Tan VH, Zhang L, Wang R, Jones PP, Napolitano C, Priori SG, Chen SRW
Biosci Rep 2021 Apr 30;41(4) doi: 10.1042/BSR20210209. PMID: 33825858Free PMC Article

Diagnosis

Diverse Phenotypic Manifestations in a Family with a Novel RYR2 E4107A Variant.
Hasegawa H, Tamura S, Nakajima T, Kawabata-Iwakawa R, Kobari T, Matsumoto N, Sano Y, Nishiyama M, Kurabayashi M, Kaneko Y, Nakatani Y, Ishii H
Int Heart J 2024;65(3):580-585. doi: 10.1536/ihj.23-652. PMID: 38825499
Calcium Release Deficiency Syndrome: A New Inherited Arrhythmia Syndrome.
Kallas D, Roberts JD, Sanatani S, Roston TM
Card Electrophysiol Clin 2023 Sep;15(3):319-329. Epub 2023 Jun 20 doi: 10.1016/j.ccep.2023.05.003. PMID: 37558302
Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor.
Przybylski R, Abrams DJ
Curr Opin Cardiol 2023 Jul 1;38(4):390-395. Epub 2023 Mar 28 doi: 10.1097/HCO.0000000000001051. PMID: 37016946
Clinical and Functional Characterization of Ryanodine Receptor 2 Variants Implicated in Calcium-Release Deficiency Syndrome.
Roston TM, Wei J, Guo W, Li Y, Zhong X, Wang R, Estillore JP, Peltenburg PJ, Noguer FRI, Till J, Eckhardt LL, Orland KM, Hamilton R, LaPage MJ, Krahn AD, Tadros R, Vinocur JM, Kallas D, Franciosi S, Roberts JD, Wilde AAM, Jensen HK, Sanatani S, Chen SRW
JAMA Cardiol 2022 Jan 1;7(1):84-92. doi: 10.1001/jamacardio.2021.4458. PMID: 34730774Free PMC Article
Identification of loss-of-function RyR2 mutations associated with idiopathic ventricular fibrillation and sudden death.
Zhong X, Guo W, Wei J, Tang Y, Liu Y, Zhang JZ, Tan VH, Zhang L, Wang R, Jones PP, Napolitano C, Priori SG, Chen SRW
Biosci Rep 2021 Apr 30;41(4) doi: 10.1042/BSR20210209. PMID: 33825858Free PMC Article

Therapy

Calcium Release Deficiency Syndrome: A New Inherited Arrhythmia Syndrome.
Kallas D, Roberts JD, Sanatani S, Roston TM
Card Electrophysiol Clin 2023 Sep;15(3):319-329. Epub 2023 Jun 20 doi: 10.1016/j.ccep.2023.05.003. PMID: 37558302
Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor.
Przybylski R, Abrams DJ
Curr Opin Cardiol 2023 Jul 1;38(4):390-395. Epub 2023 Mar 28 doi: 10.1097/HCO.0000000000001051. PMID: 37016946

Prognosis

RyR2 C-terminal truncating variants identified in patients with arrhythmic phenotypes exert a dominant negative effect through formation of wildtype-truncation heteromers.
Tian S, Zhong X, Wang H, Wei J, Guo W, Wang R, Paul Estillore J, Napolitano C, Duff HH, Ilhan E, Knight LM, Lloyd MS, Roberts JD, Priori SG, Chen SRW
Biochem J 2023 Sep 13;480(17):1379-1395. doi: 10.1042/BCJ20230254. PMID: 37492947
Clinical and Functional Characterization of Ryanodine Receptor 2 Variants Implicated in Calcium-Release Deficiency Syndrome.
Roston TM, Wei J, Guo W, Li Y, Zhong X, Wang R, Estillore JP, Peltenburg PJ, Noguer FRI, Till J, Eckhardt LL, Orland KM, Hamilton R, LaPage MJ, Krahn AD, Tadros R, Vinocur JM, Kallas D, Franciosi S, Roberts JD, Wilde AAM, Jensen HK, Sanatani S, Chen SRW
JAMA Cardiol 2022 Jan 1;7(1):84-92. doi: 10.1001/jamacardio.2021.4458. PMID: 34730774Free PMC Article

Clinical prediction guides

RyR2 C-terminal truncating variants identified in patients with arrhythmic phenotypes exert a dominant negative effect through formation of wildtype-truncation heteromers.
Tian S, Zhong X, Wang H, Wei J, Guo W, Wang R, Paul Estillore J, Napolitano C, Duff HH, Ilhan E, Knight LM, Lloyd MS, Roberts JD, Priori SG, Chen SRW
Biochem J 2023 Sep 13;480(17):1379-1395. doi: 10.1042/BCJ20230254. PMID: 37492947
Clinical and Functional Characterization of Ryanodine Receptor 2 Variants Implicated in Calcium-Release Deficiency Syndrome.
Roston TM, Wei J, Guo W, Li Y, Zhong X, Wang R, Estillore JP, Peltenburg PJ, Noguer FRI, Till J, Eckhardt LL, Orland KM, Hamilton R, LaPage MJ, Krahn AD, Tadros R, Vinocur JM, Kallas D, Franciosi S, Roberts JD, Wilde AAM, Jensen HK, Sanatani S, Chen SRW
JAMA Cardiol 2022 Jan 1;7(1):84-92. doi: 10.1001/jamacardio.2021.4458. PMID: 34730774Free PMC Article
Molecular characterization of the calcium release channel deficiency syndrome.
Tester DJ, Kim CSJ, Hamrick SK, Ye D, O'Hare BJ, Bombei HM, Fitzgerald KK, Haglund-Turnquist CM, Atkins DL, Nunez LAO, Law I, Temple J, Ackerman MJ
JCI Insight 2020 Aug 6;5(15) doi: 10.1172/jci.insight.135952. PMID: 32663189Free PMC Article

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    • ClinVar
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      Related information in GTR
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      Clinical tests in GTR
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      Related records in OMIM
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