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Cardiac arrhythmia, ankyrin-B-related

MedGen UID:
Concept ID:
Disease or Syndrome
SNOMED CT: Cardiac arrhythmia ankyrin-B related (764457005); Ankyrin-B syndrome (764457005)
Gene (location): ANK2 (4q25-26)
Monarch Initiative: MONDO:0010958
OMIM®: 600919

Alexander J Groffen  |  Hennie Bikker  |  Imke Christiaans   view full author information

Additional descriptions

From GeneReviews Overview
Long QT syndrome (LQTS) is a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the EKG that are associated with tachyarrhythmias, typically the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing a syncopal event, the most common symptom in individuals with LQTS. Such cardiac events typically occur during exercise and emotional stress, less frequently during sleep, and usually without warning. In some instances, TdP degenerates to ventricular fibrillation and causes aborted cardiac arrest (if the individual is defibrillated) or sudden death. Approximately 50% of untreated individuals with a pathogenic variant in one of the genes associated with LQTS have symptoms, usually one to a few syncopal events. While cardiac events may occur from infancy through middle age, they are most common from the preteen years through the 20s. Some types of LQTS are associated with a phenotype extending beyond cardiac arrhythmia. In addition to the prolonged QT interval, associations include muscle weakness and facial dysmorphism in Andersen-Tawil syndrome (LQTS type 7); hand/foot, facial, and neurodevelopmental features in Timothy syndrome (LQTS type 8); and profound sensorineural hearing loss in Jervell and Lange-Nielson syndrome.
Loss-of-function mutations in ANK2 can result in a broad spectrum of clinical cardiac phenotypes. Carriers of some mutations (e.g., E1425G, 106410.0001) display QT interval prolongation, stress- and/or exercise-induced polymorphic ventricular arrhythmia, syncope, and sudden cardiac death. Patients with other variants show clinical phenotypes, sometimes mild, extending beyond LQTS, leading to the label 'ankyrin-B syndrome.' These phenotypes include bradycardia, sinus arrhythmia, delayed conduction/conduction block, idiopathic ventricular fibrillation, and catecholaminergic polymorphic ventricular tachycardia (Mohler et al., 2007).  http://www.omim.org/entry/600919
From MedlinePlus Genetics
Ankyrin-B syndrome is associated with a variety of heart problems related to disruption of the heart's normal rhythm (arrhythmia). Heart rhythm is controlled by electrical signals that move through the heart in a highly coordinated way. In ankyrin-B syndrome, disruption of different steps of electrical signaling can lead to arrhythmia, and the resulting heart problems vary among affected individuals.

Individuals with ankyrin-B syndrome may have problems with the sinoatrial (SA) node, which generates the electrical impulses that start each heartbeat. If the SA node is not functioning properly, the heartbeat can be too slow (bradycardia). In a small number of people with ankyrin-B syndrome, the heart takes longer than usual to recharge between beats, which is known as a prolonged QT interval (long QT). Some affected individuals have impaired progression (conduction) of electrical impulses between the chambers of the heart, which can cause a problem called heart block. Other heart problems that occur in ankyrin-B syndrome include irregular and uncoordinated electrical activity in the heart's upper chambers (atrial fibrillation) or lower chambers (ventricular fibrillation) and an abnormality called catecholaminergic polymorphic ventricular tachycardia (CPVT), in which an increase in the heart rate can trigger an abnormally fast and irregular heartbeat called ventricular tachycardia. In people with ankyrin-B syndrome, arrhythmia can lead to fainting (syncope) or cardiac arrest and sudden death.

When associated with a prolonged QT interval, the condition is sometimes classified as long QT syndrome 4. However, because additional heart problems can result from changes in the same gene, long QT syndrome 4 is usually considered part of ankyrin-B syndrome.  https://medlineplus.gov/genetics/condition/ankyrin-b-syndrome

Clinical features

From HPO
Sudden cardiac death
MedGen UID:
Concept ID:
Pathologic Function
The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).
Atrial fibrillation
MedGen UID:
Concept ID:
An atrial arrhythmia characterized by disorganized atrial activity without discrete P waves on the surface EKG, but instead by an undulating baseline or more sharply circumscribed atrial deflections of varying amplitude an frequency ranging from 350 to 600 per minute.
MedGen UID:
Concept ID:
Sign or Symptom
Syncope is a syndrome in which loss of consciousness is of relatively sudden onset, temporary (usually less than 1 to 2 minutes), self-terminating, and of usually rapid recovery. Syncope leads to a generalized weakness of muscles with loss of postural tone, inability to stand upright, and loss of consciousness. Once the patient is in a horizontal position, blood flow to the brain is no longer hindered by gravitation and consciousness is regained. Unconsciousness usually lasts for seconds to minutes. Headache and drowsiness (which usually follow seizures) do not follow a syncopal attack. Syncope results from a sudden impairment of brain metabolism usually due to a reduction in cerebral blood flow.
Sinus bradycardia
MedGen UID:
Concept ID:
Pathologic Function
Bradycardia related to a mean resting sinus rate of less than 50 beats per minute.
Prolonged QT interval
MedGen UID:
Concept ID:
Increased time between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).

Recent clinical studies


Su L, Wu S, Wang S, Wang Z, Xiao F, Shan P, Zhou H, Huang Z, Xu L, Huang W
Europace 2019 May 1;21(5):763-770. doi: 10.1093/europace/euy281. PMID: 30561576
Swayne LA, Murphy NP, Asuri S, Chen L, Xu X, McIntosh S, Wang C, Lancione PJ, Roberts JD, Kerr C, Sanatani S, Sherwin E, Kline CF, Zhang M, Mohler PJ, Arbour LT
Circ Cardiovasc Genet 2017 Jan;10(1) doi: 10.1161/CIRCGENETICS.116.001537. PMID: 28196901Free PMC Article


Huq AJ, Pertile MD, Davis AM, Landon H, James PA, Kline CF, Vohra J, Mohler PJ, Delatycki MB
Heart Lung Circ 2017 Jun;26(6):612-618. Epub 2016 Nov 16 doi: 10.1016/j.hlc.2016.09.013. PMID: 27916589Free PMC Article


Wolf RM, Glynn P, Hashemi S, Zarei K, Mitchell CC, Anderson ME, Mohler PJ, Hund TJ
Am J Physiol Heart Circ Physiol 2013 May;304(9):H1253-66. Epub 2013 Feb 22 doi: 10.1152/ajpheart.00734.2012. PMID: 23436330Free PMC Article

Clinical prediction guides

Wolf RM, Glynn P, Hashemi S, Zarei K, Mitchell CC, Anderson ME, Mohler PJ, Hund TJ
Am J Physiol Heart Circ Physiol 2013 May;304(9):H1253-66. Epub 2013 Feb 22 doi: 10.1152/ajpheart.00734.2012. PMID: 23436330Free PMC Article

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