IllnessSudden cardiac death, differential diagnosis [2022]

NGS +

Sudden cardiac death (SCD) is an unforeseen, unexpected heart function loss that occurs within 1h of symptom onset or within 24h of last being seen alive. SCD may occur after a long history of cardiac disease, but it can also be the 1. manifestation of genetic heart disease in a seemingly healthy person. The cause of death is either cessation of heartbeat or irregular heart rhythm, both resulting in decreased tissue perfusion. SCD presents a significant cause of mortality, including ~20% of all deaths in Western societies. Coronary artery disease is responsible for 70-75% of all SCD cases in the population over the age of 35. In people aged <35 years, the rate of SCD is approximately 1–2/100000 people in the general population. The etiology of SCD in this group includes hypertrophic and dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, myocarditis and different kinds of arrhythmogenic disorders including Brugada syndrome, congenital long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Hence mutations in many genes can finally be responsible for SCD according to all classical patterns of inheritance. The molecular genetic yield hardly exceeds one third of cases.

Reference: https://jamanetwork.com/journals/jamacardiology/fullarticle/2780094

• Allelic: Atrial fibrillation, familial, 10 (SCN5A)
• Allelic: Atrial fibrillation, familial, 3 (KCNQ1)
• Allelic: Atrial fibrillation, familial, 9 (KCNJ2)
• Allelic: Becker muscular dystrophy (DMD)
• Allelic: Duchenne muscular dystrophy (DMD)
• Allelic: Heart block, nonprogressive (SCN5A)
• Allelic: Heart block, progressive, type IA (SCN5A)
• Allelic: Sick sinus syndrome 1 (SCN5A)
• Andersen syndrome (KCNJ2)
• Arrhythmogenic right ventricular dysplasia 10 (DSG2)
• Arrhythmogenic right ventricular dysplasia 11 (DSC2)
• Arrhythmogenic right ventricular dysplasia 11, mild palmoplantar keratoderma + woolly hair (DSC2)
• Arrhythmogenic right ventricular dysplasia 2 (RYR2)
• Arrhythmogenic right ventricular dysplasia 8 (DSP)
• Arrhythmogenic right ventricular dysplasia 9 (PKP2)
• Barth syndrome (TAZ)
• Brugada syndrome 1 (SCN5A)
• Brugada syndrome 3 (CACNA1C)
• Brugada syndrome 4 (CACNB2)
• Cardiac arrhythmia, ankyrin-B-related (ANK2)
• Cardiomyopathy, dilated, 1A (LMNA)
• Cardiomyopathy, dilated, 1BB (DSG2)
• Cardiomyopathy, dilated, 1C, with/-out LVNC (LDB3)
• Cardiomyopathy, dilated, 1E (SCN5A)
• Cardiomyopathy, dilated, 1G (TTN)
• Cardiomyopathy, dilated, 1I (DES)
• Cardiomyopathy, dilated, 1MM (MYBPC3)
• Cardiomyopathy, dilated, 1S (MYH7)
• Cardiomyopathy, dilated, 3B (DMD)
• Cardiomyopathy, dilated, with woolly hair + keratoderma (DSP)
• Cardiomyopathy, familial hypertrophic, 26 (FLNC)
• Cardiomyopathy, familial hypertrophic, 9 (TTN)
• Cardiomyopathy, familial restrictive 5 (FLNC)
• Cardiomyopathy, hypertrophic, 1 (MYH7)
• Cardiomyopathy, hypertrophic, 24 (LDB3)
• Cardiomyopathy, hypertrophic, 4 (MYBPC3)
• Dilated cardiomyopathy with woolly hair, keratoderma + tooth agenesis (DSP)
• Emery-Dreifuss muscular dystrophy 1, XL (EMD)
• Emery-Dreifuss muscular dystrophy 2, AD (LMNA)
• Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
• Hypertrophic cardiomyopathy [MONDO:0005045, panelapp] (TRIM63)
• Jervell + Lange-Nielsen syndrome (KCNQ1)
• Left ventricular noncompaction 10 (MYBPC3)
• Left ventricular noncompaction 3 (LDB3)
• Left ventricular noncompaction 5 (MYH7)
• Long QT syndrome 1 (KCCNQ1)
• Long QT syndrome 1, acquired, susceptibility to (KCNQ1)
• Long QT syndrome 14 (CALM1)
• Long QT syndrome 2 (KCNH2)
• Long QT syndrome 2, acquired, susceptibility to (KCNH2)
• Long QT syndrome 3 (SCN5A)
• Long QT syndrome 4 (ANK2)
• Long QT syndrome 8 (CACNA1C)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. with/-out mental retardation, type B, 5 (FKRP)
• Myotonic dystrophy 1 (DPMK_CTG)
• Naxos disease (JUP)
• Restrictive cardiomyopathy [MONDO:0005201, panelapp] (TRIM63)
• Short QT syndrome 1 (KCNH2)
• Short QT syndrome 2 (KCNQ1)
• Short QT syndrome 3 (KCNJ2)
• Sudden infant death syndrome, susceptibility to (SCN5A)
• Timothy syndrome (CACNA1C)
• Ventricular arrythmias due to cardiac RYR2 calcium release deficiency syndrome (RYR2)
• Ventricular fibrillation, familial, 1 (SCN5A)
• Ventricular tachycardia, catecholaminergic polymorphic, 1 (RYR2)
• Ventricular tachycardia, catecholaminergic polymorphic, 2 (CASQ2)
• Ventricular tachycardia, catecholaminergic polymorphic, 4 (CALM1)
• Ventricular tachycardia, catecholaminergic polymorphic, 5, with/-out muscle weakness (TRDN)