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Inclusion Criteria
Brugada syndrome diagnosed according to criteria*: - ST segment elevation with type I morphology >= 2 mm in >= 1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space occurring spontaneously OR - Type I ECG morphology as above following a provocative drug test with intravenous administration of Class I antiarrhythmic drugs AND one of - A positive family history of young sudden death OR Brugada syndrome OR - Cardiac arrest with spontaneous type I ECG pattern, OR - Documented history of VF or polymorphic VT, OR - Syncope of likely arrhythmic cause, OR - Nocturnal agonal respiration * Heart Rhythm Society/European Heart Rhythm Association Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease. In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.
Exclusion Criteria
- Unclear diagnosis or history suggestive of a non-genetic cause - Any Brugada syndrome mutation positive (if clearly pathogenic)
Prior Genetic Testing
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. - Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing. PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.
Genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: SCN5A
Closing Statement
These requirements will be kept under continual review during the main programme and may be subject to change.
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Prolonged PR interval
Increased time for the PR interval (beginning of the P wave to the beginning of the QRS complex). Comment: In adults, normal values are 120 to 200 ms long.
Atrioventricular block
Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.
Prolonged QTc interval
Shortened QT interval
Decreased time between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).
J wave
The J wave is a positive convex deflection that occurs at the junction of the QRS complex and ST segment, the J-point. Comment: J waves can be seen in hypothermia when the core body temperature falls below 32 degrees C. Then, they occur most prominently in the inferior leads: II, III, and aVF and the precordial leads: V5-V6. J waves can also be observed in other conditions such as some forms of Brugada syndrome.
Abnormal ST segment
An electrocardiographic anomaly of the ST segment, which is the segment that connects the QRS complex and the T wave. The ST segment normally has a duration of 80 to 120 ms, is flat and at the same level (isoelectric) as the PR and TP segment.
Abnormal T-wave
An abnormality of the T wave on the electrocardiogram, which mainly represents the repolarization of the ventricles.
Bundle branch block
Block of conduction of electrical impulses along the Bundle of His or along one of its bundle branches. Comment: The Bundle of His conducts the electrical impulse from the atrioventricular node into the ventricles. THe Bundle of His divides into right and left bundle branches. A universal feature of a bundle branch block is a prolongation of the time required for depolarization of a portion of the ventricles, reflected in an abnormality of the QRS complex.
Atrial fibrillation
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. Comment: The ventricular response to atrial fibrillation is irregularly irregular because of the large number of atrial impulses that transit the atrioventricular node, making the ventricle partially refractory to further impulses. Atrial fibrillation can cause a number of manifestations including excessive ventricular response with angina pectoris or hypotension in susceptible individuals, syncope, systemic embolization, fatigue, or anxiety. These features should be coded separately.
Ventricular extrasystoles
Premature ventricular contractions (PVC) or ventricular extrasystoles are premature contractions of the heart that arise in response to an impulse in the ventricles rather than the normal impulse from the sinoatrial (SA) node.
Ventricular tachycardia
Effort-induced polymorphic ventricular tachycardias
Torsade de pointes
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.
Ventricular fibrillation
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.
Sudden cardiac death
The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).
Syncope
Syncope refers 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.
Cardiac arrest
Palpitations
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Sensorineural hearing impairment
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Comment: Hearing loss caused by damage or dysfunction of the auditory nerve (cranial nerve VIII, also known as the cochlear nerve).
Seizures
Seizures are an intermittent abnormality of the central nervous system due to a sudden, excessive, disorderly discharge of cerebral neurons and characterized clinically by some combination of disturbance of sensation, loss of consciousness, impairment of psychic function, or convulsive movements. The term epilepsy is used to describe chronic, recurrent seizures. Comment: The term epilepsy is not used to describe recurrent febrile seizures. Epilepsy presumably reflects an abnormally reduced seizure threshold.
Periodic paralysis
Episodes of muscle weakness.
Intellectual disability
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70. Comment: This term should be used for children at least five years old. For younger children, consider the term Global developmental delay (HP:0001263).
Abnormal facial shape
An abnormal morphology (form) of the face or its components. Comment: This term now covers many of the historical inexact descriptions such as Bird-like facies that probably should be avoided in modern genetics. This portion of the Ontology should be revised.
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- ECG diagnostics
Cardiac measurements made using electrocardiography
- Cardiac MRI
- Holter monitor test
- Signal averaged ECG
- Exercise test - cardiac
Exercise test used as part of cardiac diagnostic testing
- Echocardiogram
Applicable to all echocardiograms, i.e. cardiomyopathy and CTD
- Electrophysiological study
Electrophysiological or EP study
- Sodium channel blocker challenge
A cardiac drug challenge using sodium channel blocker
- Alcohol intake
- Exercise status
- Epinephrine challenge
A cardiac drug challenge test using epinephrine
- Smoking status
- ECG diagnostics