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Sudden death

MedGen UID:
8257
Concept ID:
C0011071
Pathologic Function
Synonyms: Death, Sudden; Sudden Death
SNOMED CT: Sudden death (26636000)
 
HPO: HP:0001699
OMIM®: 590035

Definition

Rapid and unexpected death. [from HPO]

Term Hierarchy

Conditions with this feature

SUDDEN INFANT DEATH SYNDROME
MedGen UID:
52548
Concept ID:
C0038644
Disease or Syndrome
Sudden infant death syndrome (SIDS) is a diagnosis of exclusion which should be made only after a thorough autopsy without identification of a specific cause of death (Mage and Donner, 2004). Weese-Mayer et al. (2007) provided a detailed review of genetic factors that have been implicated in SIDS. The authors concluded that SIDS represents more than 1 entity and has a heterogeneous etiology most likely involving several different genetically controlled metabolic pathways.
Williams syndrome
MedGen UID:
59799
Concept ID:
C0175702
Disease or Syndrome
Williams syndrome (WS) is characterized by developmental delay, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, cardiovascular disease (supravalvar aortic stenosis, peripheral pulmonary stenosis, hypertension), connective tissue abnormalities, growth deficiency, endocrine abnormalities (early puberty, hypercalcemia, hypercalciuria, hypothyroidism), and distinctive facies. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones. Feeding difficulties often lead to poor weight gain in infancy.
Conduction disorder of the heart
MedGen UID:
78114
Concept ID:
C0264886
Disease or Syndrome
Any abnormal alteration of atrioventricular conduction.
Apnea, central sleep
MedGen UID:
99249
Concept ID:
C0520680
Disease or Syndrome
Sleep apnea results from a temporary loss of the central drive to the muscles responsible for breathing.
Costello syndrome
MedGen UID:
108454
Concept ID:
C0587248
Disease or Syndrome
While the majority of individuals with HRAS-related Costello syndrome (Costello syndrome) share characteristic findings affecting multiple organ systems, the phenotypic spectrum is wide, ranging from a mild or attenuated phenotype to a severe phenotype with early-lethal complications. Costello syndrome is typically characterized by failure to thrive in infancy as a result of severe postnatal feeding difficulties; short stature; developmental delay or intellectual disability; coarse facial features (full lips, large mouth, full nasal tip); curly or sparse, fine hair; loose, soft skin with deep palmar and plantar creases; papillomata of the face and perianal region; diffuse hypotonia and joint laxity with ulnar deviation of the wrists and fingers; tight Achilles tendons; and cardiac involvement including cardiac hypertrophy (usually hypertrophic cardiomyopathy), congenital heart defects (usually valvular pulmonic stenosis), and arrhythmia (usually supraventricular tachycardia, especially abnormal atrial rhythm / multifocal atrial tachycardia or ectopic atrial tachycardia). Relative or absolute macrocephaly is typical, and postnatal cerebellar overgrowth can result in the development of a Chiari I malformation with associated anomalies including hydrocephalus or syringomyelia. Individuals with Costello syndrome have an approximately 15% lifetime risk for malignant tumors including rhabdomyosarcoma and neuroblastoma in young children and transitional cell carcinoma of the bladder in adolescents and young adults.
Naxos disease
MedGen UID:
321991
Concept ID:
C1832600
Disease or Syndrome
Naxos disease (NXD) is characterized by arrhythmogenic right ventricular cardiomyopathy associated with abnormalities of the skin, hair, and nails. The ectodermal features are evident from birth or early childhood, whereas the cardiac symptoms develop in young adulthood or later. Clinical variability of ectodermal features has been observed, with hair anomalies ranging from woolly hair to alopecia, and skin abnormalities ranging from mild focal palmoplantar keratoderma to generalized skin fragility or even lethal neonatal epidermolysis bullosa (Protonotarios et al., 1986; Cabral et al., 2010; Pigors et al., 2011; Erken et al., 2011; Sen-Chowdhry and McKenna, 2014). Another syndrome involving cardiomyopathy, woolly hair, and keratoderma (DCWHK; 605676) is caused by mutation in the desmoplakin gene (DSP; 125647). Also see 610476 for a similar disorder caused by homozygous mutation in the DSC2 gene (125645).
Timothy syndrome
MedGen UID:
331395
Concept ID:
C1832916
Disease or Syndrome
The clinical manifestations of CACNA1C-related disorders include a spectrum of nonsyndromic and syndromic phenotypes, which generally correlate with the impact of the pathogenic variant on calcium current. Phenotypes can include nonsyndromic long QT syndrome (rate-corrected QT [QTc] interval >480 ms); nonsyndromic short QT syndrome (QTc <350 ms), with risk of sudden death; Brugada syndrome (ST segment elevation in right precordial leads [V1-V2]) with short QT interval; classic Timothy syndrome (prolonged QT interval, autism, and congenital heart defect) with or without unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three; and CACNA1C-related neurodevelopmental disorder, in which the features tend to favor one or more of the following: developmental delay / intellectual disability, hypotonia, epilepsy, and/or ataxia.
Sudden infant death-dysgenesis of the testes syndrome
MedGen UID:
332428
Concept ID:
C1837371
Disease or Syndrome
Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is characterized by sudden cardiac or respiratory arrest, disordered testicular development, and neurologic dysfunction, and is uniformly fatal before 1 year of age (Slater et al., 2020).
Progressive familial heart block type II
MedGen UID:
333884
Concept ID:
C1841658
Disease or Syndrome
Progressive familial heart block type II (PFHB2) is an autosomal dominant disorder, similar to type I progressive familial heart block (PFHB1; see 113900). The pattern of PFHB2, however, tends to develop along the lines of a sinus bradycardia with a left posterior hemiblock, presenting clinically as syncopal episodes, Stokes-Adams seizures, or sudden death when complete heart block supervenes (Brink and Torrington, 1977).
Dilated cardiomyopathy 1J
MedGen UID:
343105
Concept ID:
C1854368
Disease or Syndrome
Sensorineural deafness with dilated cardiomyopathy is an extremely rare autosomal dominant syndrome described in two families to date and characterized by moderate to severe sensorineural hearing loss manifesting during childhood, and associated with late-onset dilated cardiomyopathy that generally progresses to heart failure.
Arrhythmogenic right ventricular dysplasia 4
MedGen UID:
356107
Concept ID:
C1865881
Disease or Syndrome
Familial arrhythmogenic right ventricular dysplasia-4 (ARVD4) is characterized by progressive degeneration of the myocardium of the right ventricle, with focal necrosis of muscle cells followed by adipose and connective tissue replacement. The left ventricle may be partially involved. Patches of replacement tissue result in electrical instability and arrhythmias. Patients experience syncopal episodes, and sudden death may occur (summary by Rampazzo et al., 1997). For phenotypic information and evidence of genetic heterogeneity in this disorder, see ARVD1 (107970).
Progressive familial heart block, type 1A
MedGen UID:
406301
Concept ID:
C1879286
Disease or Syndrome
Progressive familial heart block type I (PFHBI, PFHB1) is an autosomal dominant cardiac bundle branch disorder that may progress to complete heart block (Brink and Torrington, 1977; van der Merwe et al., 1986; van der Merwe et al., 1988). It is defined on electrocardiogram by evidence of bundle branch disease, i.e., right bundle branch block, left anterior or posterior hemiblock, or complete heart block, with broad QRS complexes. Progression has been shown from a normal electrocardiogram to right bundle branch block and from the latter to complete heart block. These electrocardiographic features differentiate PFHB type I from progressive familial heart block type II (PFHBII, PFHB2; 140400), in which the onset of complete heart block is associated with narrow complexes. Electrocardiographically the changes represent, respectively, bundle branch disease (PFHB1) and atrioventricular nodal disease with an atrioventricular block and an idionodal escape rhythm (PFHB2). PFHBI is manifested symptomatically when complete heart block supervenes, either with dyspnea, syncopal episodes, or sudden death. Treatment, which is best managed by regular electrocardiographic follow-up, is by the timely implantation of a pacemaker (Brink et al., 1995). Genetic Heterogeneity of Progressive Familial Heart Block Type I Progressive familial heart block type IB (PFHB1B; 604559) is caused by mutation in the TRPM4 gene (606936) on chromosome 19q13.32.
Catecholaminergic polymorphic ventricular tachycardia 2
MedGen UID:
393837
Concept ID:
C2677794
Disease or Syndrome
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic syncope occurring during exercise or acute emotion. The underlying cause of these episodes is the onset of fast ventricular tachycardia (bidirectional or polymorphic). Spontaneous recovery may occur when these arrhythmias self-terminate. In other instances, ventricular tachycardia may degenerate into ventricular fibrillation and cause sudden death if cardiopulmonary resuscitation is not readily available. The mean onset of symptoms (usually a syncopal episode) is between age seven and 12 years; onset as late as the fourth decade of life has been reported. If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% have one or more syncopal spells. Sudden death may be the first manifestation of the disease.
Aortic aneurysm, familial thoracic 7
MedGen UID:
462427
Concept ID:
C3151077
Disease or Syndrome
Aneurysm-osteoarthritis syndrome
MedGen UID:
462437
Concept ID:
C3151087
Disease or Syndrome
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, and cervical spine malformation and/or instability), craniofacial features (hypertelorism, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant.
Catecholaminergic polymorphic ventricular tachycardia 3
MedGen UID:
462813
Concept ID:
C3151463
Disease or Syndrome
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic syncope occurring during exercise or acute emotion. The underlying cause of these episodes is the onset of fast ventricular tachycardia (bidirectional or polymorphic). Spontaneous recovery may occur when these arrhythmias self-terminate. In other instances, ventricular tachycardia may degenerate into ventricular fibrillation and cause sudden death if cardiopulmonary resuscitation is not readily available. The mean onset of symptoms (usually a syncopal episode) is between age seven and 12 years; onset as late as the fourth decade of life has been reported. If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% have one or more syncopal spells. Sudden death may be the first manifestation of the disease.
Hypertrophic cardiomyopathy 1
MedGen UID:
501195
Concept ID:
C3495498
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is typically defined by the presence of unexplained left ventricular hypertrophy (LVH). Such LVH occurs in a non-dilated ventricle in the absence of other cardiac or systemic disease capable of producing the observed magnitude of increased LV wall thickness, such as pressure overload (e.g., long-standing hypertension, aortic stenosis) or storage/infiltrative disorders (e.g., Fabry disease, amyloidosis). The clinical manifestations of HCM range from asymptomatic LVH to progressive heart failure to sudden cardiac death (SCD), and vary from individual to individual even within the same family. Common symptoms include shortness of breath (particularly with exertion), chest pain, palpitations, orthostasis, presyncope, and syncope. Most often the LVH of HCM becomes apparent during adolescence or young adulthood, although it may also develop late in life, in infancy, or in childhood.
Hypertrophic cardiomyopathy 21
MedGen UID:
766356
Concept ID:
C3553442
Disease or Syndrome
Hypertrophic cardiomyopathy (CMH) is characterized by unexplained cardiac hypertrophy: thickening of the myocardial wall in the absence of any other identifiable cause for left ventricular hypertrophy such as systemic hypertension or valvular heart disease. Myocyte hypertrophy, disarray, and fibrosis are the histopathologic hallmarks of this disorder. Clinical features are diverse and include arrhythmias, sudden cardiac death, and heart failure. With an estimated prevalence of 1 in 500, CMH is the most common cardiovascular genetic disease and the most common cause of sudden death in competitive athletes in the United States (summary by Song et al., 2006). For a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy, see CMH1 (192600).
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
MedGen UID:
778253
Concept ID:
C3711645
Disease or Syndrome
Long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and trifunctional protein (TFP) deficiency are caused by impairment of mitochondrial TFP. TFP has three enzymatic activities – long-chain enoyl-CoA hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and long-chain 3-ketoacyl-CoA thiolase. In individuals with LCHAD deficiency, there is isolated deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase, while deficiency of all three enzymes occurs in individuals with TFP deficiency. Individuals with TFP deficiency can present with a severe-to-mild phenotype, while individuals with LCHAD deficiency typically present with a severe-to-intermediate phenotype. Neonates with the severe phenotype present within a few days of birth with hypoglycemia, hepatomegaly, encephalopathy, and often cardiomyopathy. The intermediate phenotype is characterized by hypoketotic hypoglycemia precipitated by infection or fasting in infancy. The mild (late-onset) phenotype is characterized by myopathy and/or neuropathy. Long-term complications include peripheral neuropathy and retinopathy.
Long QT syndrome 14
MedGen UID:
864108
Concept ID:
C4015671
Disease or Syndrome
LQT14 is a cardiac arrhythmia disorder characterized by ventricular arrhythmias, often life-threatening, occurring very early in life, frequent episodes of T-wave alternans, markedly prolonged QTc intervals, and intermittent 2:1 atrioventricular block (Crotti et al., 2013). Patients with LQT14, LQT15 (616249), or LQT16 (618782), resulting from mutation in calmodulin genes CALM1, CALM2 (114182), or CALM3 (114183), respectively, typically have a more severe phenotype, with earlier onset, profound QT prolongation, and a high predilection for cardiac arrest and sudden death, than patients with mutations in other genes (Boczek et al., 2016).
Sclerosteosis 1
MedGen UID:
1642815
Concept ID:
C4551483
Disease or Syndrome
SOST-related sclerosing bone dysplasias include SOST-related sclerosteosis and SOST-related endosteal hyperostosis, van Buchem type (van Buchem disease), both disorders of progressive bone overgrowth due to increased bone formation. The major clinical features of SOST-related sclerosteosis are progressive skeletal overgrowth, most pronounced in the skull and mandible, and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly. Facial distortion due to frontal bossing and mandibular overgrowth is seen in nearly all individuals and becomes apparent in early childhood with progression into adulthood. Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the seventh cranial nerve (leading to facial palsy) with other, less common nerve entrapment syndromes including visual loss (2nd cranial nerve), neuralgia or anosmia (5th cranial nerve), and sensorineural hearing loss (8th cranial nerve). In SOST-related sclerosteosis, hyperostosis of the calvarium reduces intracranial volume, increasing the risk for potentially lethal elevation of intracranial pressure. Survival of individuals with SOST-related sclerosteosis into old age is unusual but not unprecedented. The manifestations of van Buchem disease are generally milder than SOST-related sclerosteosis. Stature is typically normal, cranial nerve entrapment of the seventh and eighth cranial nerves are common, and increased intracranial pressure is rare, seen only in severely affected individuals. Individuals with van Buchem disease do not have syndactyly or other digit deformities. Life span appears not to be altered.

Professional guidelines

PubMed

Maron BJ, Desai MY, Nishimura RA, Spirito P, Rakowski H, Towbin JA, Dearani JA, Rowin EJ, Maron MS, Sherrid MV
J Am Coll Cardiol 2022 Feb 1;79(4):390-414. doi: 10.1016/j.jacc.2021.11.021. PMID: 35086661
International Hypoglycaemia Study Group
Lancet Diabetes Endocrinol 2019 May;7(5):385-396. Epub 2019 Mar 27 doi: 10.1016/S2213-8587(18)30315-2. PMID: 30926258
Baruteau AE, Perry JC, Sanatani S, Horie M, Dubin AM
Eur J Pediatr 2016 Feb;175(2):151-61. Epub 2016 Jan 16 doi: 10.1007/s00431-015-2689-z. PMID: 26780751

Recent clinical studies

Etiology

Holmstrom L, Junttila J, Chugh SS
J Am Coll Cardiol 2024 Dec 3;84(23):2308-2324. Epub 2024 Nov 6 doi: 10.1016/j.jacc.2024.09.016. PMID: 39503654
Harmon KG
Clin Sports Med 2022 Jul;41(3):369-388. doi: 10.1016/j.csm.2022.02.002. PMID: 35710267
Kumar A, Avishay DM, Jones CR, Shaikh JD, Kaur R, Aljadah M, Kichloo A, Shiwalkar N, Keshavamurthy S
Rev Cardiovasc Med 2021 Mar 30;22(1):147-158. doi: 10.31083/j.rcm.2021.01.207. PMID: 33792256
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Diagnosis

Braunwald E
Am J Cardiol 2024 Feb 1;212S:S1-S3. Epub 2024 Jan 29 doi: 10.1016/j.amjcard.2023.10.075. PMID: 38368032
Finocchiaro G, Westaby J, Sheppard MN, Papadakis M, Sharma S
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Therapy

Afzali Rubin M, Svensson TL, Herling SF, Jabre P, Møller AM
Cochrane Database Syst Rev 2023 May 9;5(5):CD013619. doi: 10.1002/14651858.CD013619.pub2. PMID: 37159193Free PMC Article
Fernandes GC, Fernandes A, Cardoso R, Penalver J, Knijnik L, Mitrani RD, Myerburg RJ, Goldberger JJ
Heart Rhythm 2021 Jul;18(7):1098-1105. Epub 2021 Mar 20 doi: 10.1016/j.hrthm.2021.03.028. PMID: 33757845
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Prognosis

Berthome P, Tixier R, Briand J, Geoffroy O, Babuty D, Mansourati J, Jesel L, Dupuis JM, Bru P, Kyndt F, Guyomarch B, Thollet A, Behar N, Mabo P, Sacher F, Probst V, Gourraud JB
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Clinical prediction guides

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Recent systematic reviews

Maron BJ, Desai MY, Nishimura RA, Spirito P, Rakowski H, Towbin JA, Dearani JA, Rowin EJ, Maron MS, Sherrid MV
J Am Coll Cardiol 2022 Feb 1;79(4):390-414. doi: 10.1016/j.jacc.2021.11.021. PMID: 35086661
Galić E, Bešlić P, Kilić P, Planinić Z, Pašalić A, Galić I, Ćubela VV, Pekić P
Acta Clin Croat 2021 Dec;60(4):739-748. doi: 10.20471/acc.2021.60.04.22. PMID: 35734489Free PMC Article
Adler A, Novelli V, Amin AS, Abiusi E, Care M, Nannenberg EA, Feilotter H, Amenta S, Mazza D, Bikker H, Sturm AC, Garcia J, Ackerman MJ, Hershberger RE, Perez MV, Zareba W, Ware JS, Wilde AAM, Gollob MH
Circulation 2020 Feb 11;141(6):418-428. Epub 2020 Jan 27 doi: 10.1161/CIRCULATIONAHA.119.043132. PMID: 31983240Free PMC Article
Smith GC, Pell JP
BMJ 2003 Dec 20;327(7429):1459-61. doi: 10.1136/bmj.327.7429.1459. PMID: 14684649Free PMC Article
Maron BJ
JAMA 2002 Mar 13;287(10):1308-20. doi: 10.1001/jama.287.10.1308. PMID: 11886323

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