The patients suffering from Brugada syndrome may present to a doctor with various complaints, however, most frequently, these complaints are related to cardiovascular system and/or alterations in electrocardiographic (ECG) patterns.

Syncope is one of the most common manifestations of Brugada syndrome.

Cardiac arrest is another common presentation in these patients.
The patients of Brugada syndrome sometimes complain of nightmares.

Atrial fibrillation is the presentation in about 20% of the cases of Brugada syndrome [7].

Sometimes fever is reported and it also triggers the cardiac events in patients of Brugada syndrome.

Heart murmurs are also present in Brugada syndrome.

• Fever

  Treatment Treatment involves aggressive management of fevers with medications to reduce fever such as Paracetamol (as fever of any origin can trigger dangerous arrhythmias in this context), and avoidance of certain drugs, as listed on Brugada drugs to [cidg.org.nz]

  […] pattern in V1 (coved) and V2 (slight saddle back) Impression: Brugada syndrome unmasked by fever. [emergencymedicinecases.com]

  History of present illness: A 56-year-old male, with a history of hypertension, diabetes, and dyslipidemia, presented with chest pain, fever, and abdominal pain associated with diarrhea, one day post colonoscopy, for which an electrocardiogram (ECG) was [jetem.org]

  Bacterial infections were the commonest cause of fever in patients with BrS. All BTEP changes resolved with defervesence of fever except in one. [ncbi.nlm.nih.gov]

• Asymptomatic

  As explained in detail elsewhere ( 31 ), there are strong clinical and experimental data suggesting that quinidine could do for asymptomatic Brugada syndrome what beta-blockers have done for asymptomatic long-QT syndrome. [onlinejacc.org]

  Drug-induced BS was related to a better prognosis only in asymptomatic individuals. CONCLUSION: Drug-induced BS has a good prognosis if asymptomatic; however, SCD is possible. [ncbi.nlm.nih.gov]

  In 2018 a meta-analysis of 7 large prospective studies focused on the study of over 1,500 asymptomatic patients without ICD. Enrolled patients were at low risk (85% asymptomatic, and 50% with a drug test-induced type 1 pattern). [escardio.org]

  None None Patient no. 7: ECG Type 2, family history of SCD Asymptomatic 29 0 Asymptomatic None None Patient no. 8: ECG Type 1, EPS + hydroquinidine Asymptomatic 34 0 Asymptomatic None None Patient no. 9: ECG Type 1, EPS + family history of SCD Epileptic [doi.org]

• Weakness

  Having a history of progressive muscular weakness and gradual loss of visual acuity, he was referred to us by his ophthalmologist for risk assessment of undergoing cataract surgery. [ncbi.nlm.nih.gov]

  Case 1: 50 year old with lightheadness Case 2: 50 year old with diabetes, presenting with shortness of breath and weakness Case 3: 50 year old with one week of exertional chest pain, now constant. [emergencymedicinecases.com]

  Consequently, sex is a weak prognosticator in Brugada syndrome ( 10 ). [onlinejacc.org]

• Collapse

  While awaiting discharge had a third collapse followed by cardiac arrest with shockable rhythm. [hindawi.com]

  The Blueprint Genetics Brugada syndrome panel covers classical genes associated with Brugada syndrome, cardiac arrest underlying cardiac condition, cardiac arrest cause unspecified, syncope and collapse and abnormal ECG. [blueprintgenetics.com]

  This effect combined with the following collapse can make a strong and dramatic impression on bystanders. The weakness of the legs causes most sufferers to sit or lie down if there is time to do so. [en.wikipedia.org]

  If another person has collapsed with a cardiac arrest: Call triple zero (000) and ask for an ambulance. If calling triple zero (000) does not work on your mobile, try calling 112. (This number is only for mobile phones.) [healthdirect.gov.au]

  The patient collapsed in cardiorespiratory arrest with a rhythm which responded to defibrillation at the scene and again on transfer to hospital. 1 The present case highlights the fact that patients with Brugada syndrome can also present with syncope [emj.bmj.com]

• Unconsciousness

  > Upon arrival, 8 minutes after call was collected, the crew found patient on the floor in a state of CAt (unconscious, without breathing or pulse), while his mother was delivering basic life support (BLS) measures: sternal compression and artificial [rucont.ru]

  If you are with someone who falls unconscious and stops breathing, call the emergency number immediately. It is important to tell your doctor if you have a first-degree relative with Brugada Syndrome such as parents, siblings or children. [hom.com.au]

  A witness who stopped to help found him slumped unconscious over the steering wheel, and he regained consciousness a few seconds later. On arrival in hospital he was fully alert although he felt light headed and had mild chest discomfort. [emj.bmj.com]

• Vomiting

  Treatment Prevention Avoid drugs on the brugadadrugs.org list Keep well hydrated, especially if vomiting and diarrhea Reduce fever and keep it down; avoid heat exhaustion Take an omega-3 fish oil supplement Avoid excessive alcohol Strictly avoid marijuana [sads.org]

  There was no history of vomiting, tinnitus, and loss of weight or appetite. Three-generation family history was looked into and showed that his brothers died at an early age. [karger.com]

  • Prolonged (longer than a day) or severe episodes of vomiting or diarrhoea can affect your sodium and potassium levels. You should discuss this situation with your doctor who may prescribe oral rehydration supplements. [home.bt.com]

  Prolonged (longer than a day) or severe episodes of vomiting or diarrhoea can affect your sodium and potassium levels. You should discuss this with your doctor who may prescribe oral rehydration supplements. [bhf.org.uk]

  […] painkillers such as paracetamol to bring it down; get medical advice as soon as possible if this doesn't help drinking too much alcohol – avoid drinking lots of alcohol in a short space of time dehydration – get medical advice if you have diarrhoea or vomiting [nhs.uk]

• Nausea

  These processes cause the typical symptoms of fainting: pale skin, rapid breathing, nausea and weakness of the limbs, particularly of the legs. If the ischaemia is intense or prolonged, limb weakness progresses to collapse. [en.wikipedia.org]

  The patient specified two episodes of nausea, both after standing up, which were classified as orthostatic. He had never fainted, never noticed tachycardia or woken abruptly during sleep. [tidsskriftet.no]

  Besides these, syncope was present in 18%, abdominal pain in 8%, chest pain in 7%, arthralgia in 4%, nausea and vomiting in 4%, and pleuritic chest pain in 3%. The most common associated comorbidity was pneumonia, present in 30% of patients. [tandfonline.com]

• Tachycardia

  This report documents a case of Brugada syndrome and polymorphic ventricular tachycardia-ventricular fibrillation not initially recognized in a patient taking nortriptyline and experiencing syncope. [ncbi.nlm.nih.gov]

  Adenosine-induced, sudden bradycardia and subsequent tachycardia have also been investigated to identify QT changes of diagnostic value in patients with LQTS. [doi.org]

• Heart Disease

  Brugada syndrome (BrS) is a cardiac ion channel disease that is caused by an autosomal dominant genetic abnormality. A ventricular septal defect is a common congenital heart disease, in which genetic defects play a significant role. [ncbi.nlm.nih.gov]

  EKG Right bundle branch block; persistent ST-segment elevation in V1 to V3, unexplained by electrolyte disturbances; ischaemia; structural heart disease. Management Implantable defibrillator. [medical-dictionary.thefreedictionary.com]

• Palpitations

  Three patients (27%) reported palpitations documented by ILRs as supra-ventricular tachycardias. [doi.org]

  Symptoms include palpitations, sudden loss of consciousness or sudden cardiac death. Brugada Syndrome - How to prevent? There is no prevention. [singhealth.com.sg]

  At this presentation, he developed palpitation and VT with the same morphology at the peak exercise on a treadmill with appearance of typical ECG pattern for Brugada syndrome (BrS). [ncbi.nlm.nih.gov]

• Hypotension

  The 56 clinical analysis of traumatic intracranial hypotension syndrome(TIHS); 外伤性低颅压综合症56例临床分析 2. A probe into treatment of athletes third lumbar vertebrae transverse process syndrome; 运动员腰椎3横突综合症的治疗方法探讨 3. [dictall.com]

  However, the resulting "transient orthostatic hypotension" does not necessarily signal any serious underlying disease. [en.wikipedia.org]

  […] beta-adrenergic agonist of choice and has been reported to restore elevated ST segments to the pretreatment level in patients undergoing a challenge test with pilsicainide. [51] Atropine and ephedrine have been used for the treatment of bradycardia and hypotension [annals.in]

• Dizziness

  Dizziness due to vertigo was not enough. [hqmeded-ecg.blogspot.com]

  Four patients did not trigger the ILR recordings during four syncopes and two episodes of dizziness. Two patients triggered the device while suffering from chest pain. [doi.org]

  This case report describes a patient who presented with chest pain and dizziness along with a positive family history of sudden cardiac deaths below the age of 45 years. [karger.com]

  The patient also reported pain along the right shoulder blade and ipsilateral pleuritic chest pain, headache, and dizziness without any loss of consciousness. [austinpublishinggroup.com]

  It can cause dizziness or, in serious cases, cardiac arrest. Your heartbeat is controlled by electrical impulses. This causes your heart to beat regularly and pump blood round your body. [healthdirect.gov.au]

Brugada syndrome requires complete work-up and laboratory investigations for proper diagnosis. The investigations relevant to Brugada syndrome are listed below:

• Genetic testing has an important role in the diagnosis of the patients of Brugada syndrome. In addition to the diagnosis, genetic testing can help in identifying the relatives who are at risk for developing Brugada syndrome. [8]

• Electrocardiography (ECG) is the key investigation for the patients of Brugada syndrome. This is because some patients of Brugada syndrome may apparently be asymptomatic but still have the underlying electrocardiographic changes of this disease. For diagnostic purposes, these changes can also be induced by administration of some anti-arrhythmic drugs. Brugada syndrome has three different electrocardiographic patterns: ST-elevation (type 1), Saddleback pattern (type 2), A combination of type 1 or type 2.

• Brugada syndrome can be investigated by inducing arrhythmias with the use of electro-physiologic studies (EPS).

• Serum calcium and potassium levels should be evaluated because variations in their levels can produce the same electrocardiographic patterns as commonly seen in Brugada syndrome.

• Creatine kinase MB (CK-MB) and troponin levels should be evaluated to rule out any underlying heart condition e.g. acute coronary syndrome (ACS).

• Echocardiography and Magnetic resonance imaging (MRI) are used to rule out any arrhythmogenic condition that mimics Brugada syndrome.

• Right Bundle Branch Block

  Significant findings: ECG shows an incomplete right bundle branch block (blue arrow) with coved ST segment elevation and an inverted T wave in V1 (red arrow) and ST segment elevation in V2 (black arrow). [jetem.org]

  KEYWORDS: Brugada syndrome; ajmaline challenge; arrhythmia; depolarization; electrocardiography; endocardium; epicardium; repolarization; right bundle branch block; right ventricular outflow tract; sudden death [ncbi.nlm.nih.gov]

  1998, vol. 97 (pg. 457 - 460 ) [35] Familial cardiomyopathy underlies syndrome of right bundle branch block, ST segment elevation and sudden death, J Am Coll Cardiol, 1996, vol. 27 (pg. 443 - 448 ) [36] Pathologic substrates of right bundle branch block [doi.org]

  EKG Right bundle branch block; persistent ST-segment elevation in V1 to V3, unexplained by electrolyte disturbances; ischaemia; structural heart disease. Management Implantable defibrillator. [medical-dictionary.thefreedictionary.com]

The best option for the treatment of syncope and cardiac arrest in the patients of Brugada syndrome is the placement of an automatic implantable cardiac defibrillator (ICD). As mentioned earlier, the patients suffering from Brugada syndrome usually die of ventricular fibrillation. If a defibrillating device is in place, episodes of ventricular fibrillation will be promptly reversed and the patient’s life will be saved.

Recent studies have shown that quinidine decreases the episodes of ventricular defibrillation [9]. It may also be used for the treatment of Brugada syndrome in selected cases.

Regular exercise should be stopped as it increases the vagal tone, thereby increasing the risk of ventricular fibrillation.
Long term follow up is necessary for all the patients suffering from Brugada syndrome.

Prognosis depends largely upon the long term proper follow-up. Prognosis is good with proper treatment and management.

Without treatment, sudden cardiac death occurs in men under 40 years of age. With proper placement of implanted cardiac defibrillator, life expectancy and quality of life are improved.

The mean age of sudden death in patients suffering from Brugada syndrome is 41+/- 15 years [10].

Brugada syndrome is primarily caused by mutations in SCN5A gene, although mutations in other genes are also seen in some cases [5]. Variants of Brugada syndrome can be caused by the mutations in the genes that code subunits of the L-type calcium channel (CACNA1C and CACNB2).

Some cases of Brugada syndrome also carry mutations in GPD1-L and SCN1B genes. Besides, some conditions and diseases can exaggerate or unmask electrocardiographic changes of Brugada syndrome. Some of them are listed below.

• Fever can cause variations in electrocardiographic (ECG) pattern in patients of Brugada syndrome [6].
• Potassium level homeostasis is of prime important in cases of Brugada syndrome. This is because both hypokalemia and hyperkalemia can cause exaggeration of Brugada syndrome.
• As with potassium, monitoring of the calcium level is also important in cases of Brugada syndrome because fluctuations of calcium level can exacerbate the condition.
• Alcohol or cocaine abuse also causes exacerbation of the condition.
• Medications like sodium channel blockers, vagotonic agents, alpha adrenergic agonists, beta adrenergic blockers, heterocyclic antidepressants, and a combination of glucose and insulin cause worsening of Brugada syndrome and associated electrocardiographic changes.

Brugada syndrome is predominantly a disease of Asian people. It is much less common in the Western world. It is also much more prevalent in men as compared to women [4].

Several different mutations can result in Brugada syndrome. The underlying pathophysiology therefore varies with different genes. The voltage gated sodium channels of the heart are encoded by the SCN5A gene. Therefore, when the mutation is in the SCN5A gene - the most common mutation in Brugada syndrome - the cardiac voltage gated sodium channels do not function normally.

Abnormal voltage-gated sodium channels directly affect the cardiac action potential by reducing the sodium current available during the phases 0 (upstroke) and 1 (early repolarization). This reduction in sodium current then affects the endocardium of the right ventricle and leads to the clinical manifestations as well as the electrocardiographic variations that characterize Brugada syndrome.

The T wave remains upright and causes a saddleback electrocardiographic pattern when the usual time duration of repolarization is not changed.

Mutations in Glycerol-3-phosphate dehydrogenase 1-like (GPD1L) gene are also seen in some patients of Brugada syndrome. This gene acts as ion channel modulator in the heart muscle.

There are no guidelines for prevention of Brugada syndrome.

Brugada syndrome is a clinic-pathological entity that is characterized by an increased risk of sudden cardiac death as well as certain electrocardiographic (ECG) changes in the heart; most commonly the elevation of the ST segment in the precordial leads.

Brugada syndrome is a genetically pre-determined condition. The pattern of inheritance is autosomal dominant in as many as 50% of the familial cases. Brugada syndrome is the major cause of sudden unexplained death syndrome (SUDS) [1].

It is known to be one of the major causes of sudden death in young men without any previously diagnosed cardiac disorders [2].

Sudden death in Brugada syndrome results from ventricular fibrillation and arrhythmias. Electrocardiographic changes are observed in the patients who survive cardiac arrest [3].

Brugada syndrome is a genetic disease that affects the heart at a cellular level. In some patients, it produces no symptoms and remains undetected. In others, it causes symptoms related to the heart.

The patients who receive proper treatment and follow-up have a good prognosis. If untreated, it can cause sudden death in young patients (below 40 years of age) even in the absence of other heart diseases.

1. Nademanee K, Veerakul, G, Nimmannit, S. Arrhythmogenic marker for the sudden unexplained death syndrome in thai men. Circulation. 1997;96(8):2595-2600.
2. Brugada J, Brugada, P, Brugada, R. The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--Brugada syndrome. Europace. 1999;1(3):156-166. 
3. Martini B, Nava, A,Thiene, G. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J. 1989;118(6):1203-1209.
4. Antzelevitch C, Brugada, P, Brugada, J, Brugada, R. Brugada syndrome:from cell to bedside. Curr Probl Cardiol 2005;30(1):9-54.
5. Kapplinger J, Tester, DJ, Alders, M, Benito, B, Berthet, M, Brugada, J. An international compendium of mutations in the SCN5A encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010;7(1):33-46.
6. Amin AS, Klemens CA, Verkerk AO, et al. Fever-triggered ventricular arrhythmias in Brugada syndrome and type 2 long-QT syndrome. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. Mar 2010;18(3):165-169.
7. Bordachar P, Reuter, S, Garrigue, S, Cai, X, Hocini, M, Jais, P, et al. Incidence, clinical implications and prognosis of atrial arrhythmias in Brugada syndrome. Eur Heart J. 2004;25(10):879-884.
8. Kaufman ES. Genetic testing in Brugada syndrome. Journal of the American College of Cardiology. Oct 9 2012;60(15):1419-1420.
9. Belhassen B, Glick, A, Viskin, S. Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation. 2004;110(13):1731-1737.
10. Antzelevitch C, Brugada, P, Borggrefe, M, Brugada, J, Brugada, R, Corrado, D, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Ryhthm Society and the European Heart Rhythm Association. Circulation. 2005;111(5):659-670.