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Ebstein anomaly

MedGen UID:
4435
Concept ID:
C0013481
Congenital Abnormality
Synonyms: Ebstein anomaly of the tricuspid valve; Ebstein's anomaly; Ebstein's anomaly of the tricuspid valve
SNOMED CT: Ebstein anomaly of tricuspid valve (204357006); Ebsteins anomaly (204357006); Ebstein's anomaly (204357006); Ebstein's anomaly of tricuspid valve (204357006); Ebstein's malformation of tricuspid valve (204357006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
HPO: HP:0010316
Monarch Initiative: MONDO:0009144
OMIM®: 224700
Orphanet: ORPHA1880

Definition

Ebstein anomaly is characterized by downward displacement of variable severity of the tricuspid valve into the right ventricle. The valve leaflets may be dysplastic, and a variable portion of the proximal part of the right ventricle is in continuity with the right atrium ('atrialized'), because of the abnormally positioned tricuspid valve. The severity of this defect includes a spectrum ranging from severe disturbance in fetal and neonatal life to virtually asymptomatic survival to adult life. Associated extracardiac anomalies in the setting of chromosomal or mendelian disorders occur in about 20% of patients with Ebstein anomaly. Nonsyndromic Ebstein anomaly can occur as a sporadic or a familial defect (summary by Digilio et al., 2011). [from OMIM]

Additional description

From MedlinePlus Genetics
People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.

Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.

Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.

Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.  https://medlineplus.gov/genetics/condition/critical-congenital-heart-disease

Clinical features

From HPO
Sudden cardiac death
MedGen UID:
38841
Concept ID:
C0085298
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:
445
Concept ID:
C0004238
Finding
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.
Ebstein anomaly
MedGen UID:
4435
Concept ID:
C0013481
Congenital Abnormality
Ebstein anomaly is characterized by downward displacement of variable severity of the tricuspid valve into the right ventricle. The valve leaflets may be dysplastic, and a variable portion of the proximal part of the right ventricle is in continuity with the right atrium ('atrialized'), because of the abnormally positioned tricuspid valve. The severity of this defect includes a spectrum ranging from severe disturbance in fetal and neonatal life to virtually asymptomatic survival to adult life. Associated extracardiac anomalies in the setting of chromosomal or mendelian disorders occur in about 20% of patients with Ebstein anomaly. Nonsyndromic Ebstein anomaly can occur as a sporadic or a familial defect (summary by Digilio et al., 2011).
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Right bundle branch block
MedGen UID:
88445
Concept ID:
C0085615
Disease or Syndrome
A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG.
Atrial standstill
MedGen UID:
639047
Concept ID:
C0541782
Pathologic Function
Atrial standstill or silent atrium is a rare condition presenting with the absence of electrical and mechanical activity in the atria. It presents with the absence of P waves, bradycardia, and wide QRS complex in the electrocardiogram.
Ventricular preexcitation
MedGen UID:
107848
Concept ID:
C0559106
Disease or Syndrome
An abnormality in which the cardiac ventricles depolarize too early as a result of an abnormality of cardiac conduction pathways such as an accessory pathway.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEbstein anomaly
Follow this link to review classifications for Ebstein anomaly in Orphanet.

Conditions with this feature

Down syndrome
MedGen UID:
4385
Concept ID:
C0013080
Disease or Syndrome
Down syndrome, the most frequent form of mental retardation caused by a microscopically demonstrable chromosomal aberration, is characterized by well-defined and distinctive phenotypic features and natural history. It is caused by triplicate state (trisomy) of all or a critical portion of chromosome 21.
Ebstein anomaly
MedGen UID:
4435
Concept ID:
C0013481
Congenital Abnormality
Ebstein anomaly is characterized by downward displacement of variable severity of the tricuspid valve into the right ventricle. The valve leaflets may be dysplastic, and a variable portion of the proximal part of the right ventricle is in continuity with the right atrium ('atrialized'), because of the abnormally positioned tricuspid valve. The severity of this defect includes a spectrum ranging from severe disturbance in fetal and neonatal life to virtually asymptomatic survival to adult life. Associated extracardiac anomalies in the setting of chromosomal or mendelian disorders occur in about 20% of patients with Ebstein anomaly. Nonsyndromic Ebstein anomaly can occur as a sporadic or a familial defect (summary by Digilio et al., 2011).
Dilated cardiomyopathy 1S
MedGen UID:
371831
Concept ID:
C1834481
Disease or Syndrome
Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the MYH7 gene.
Chromosome 1p36 deletion syndrome
MedGen UID:
334629
Concept ID:
C1842870
Disease or Syndrome
The constitutional deletion of chromosome 1p36 results in a syndrome with multiple congenital anomalies and mental retardation (Shapira et al., 1997). Monosomy 1p36 is the most common terminal deletion syndrome in humans, occurring in 1 in 5,000 births (Shaffer and Lupski, 2000; Heilstedt et al., 2003). See also neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH; 616975), which shows overlapping features and is caused by heterozygous mutation in the RERE gene (605226) on proximal chromosome 1p36. See also Radio-Tartaglia syndrome (RATARS; 619312), caused by mutation in the SPEN gene (613484) on chromosome 1p36, which shows overlapping features.
Dilated cardiomyopathy 1Y
MedGen UID:
437215
Concept ID:
C2678476
Disease or Syndrome
Dilated cardiomyopathy-1Y (CMD1Y) is characterized by severe progressive cardiac failure, resulting in death in the third to sixth decades of life in some patients. Electron microscopy shows an abnormal sarcomere structure (Olson et al., 2001). In left ventricular noncompaction-9 (LVNC9), patients may present with cardiac failure or may be asymptomatic. Echocardiography shows noncompaction of the apex and midventricular wall of the left ventricle (Probst et al., 2011). Some patients also exhibit Ebstein anomaly of the tricuspid valve (Kelle et al., 2016) and some have mitral valve insufficiency (Nijak et al., 2018).
BNAR syndrome
MedGen UID:
413305
Concept ID:
C2750433
Disease or Syndrome
FREM1 autosomal recessive disorders include: Manitoba oculotrichoanal (MOTA) syndrome, bifid nose with or without anorectal and renal anomalies (BNAR syndrome), and isolated congenital anomalies of kidney and urinary tract (CAKUT). MOTA syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (widely spaced eyes, anophthalmia/microphthalmia and/or cryptophthalmos, colobomas of the upper eyelid, and corneopalpebral synechiae), nose (bifid or broad nasal tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal. BNAR syndrome is characterized by a bifid or wide nasal tip, anorectal anomalies, and renal malformations (e.g., renal agenesis, renal dysplasia). Typically the eye manifestations of MOTA syndrome are absent. FREM1-CAKUT was identified in one individual with bilateral vesicoureteral reflux (VUR) and a second individual with VUR and renal hypodysplasia.
Cardiomyopathy, dilated, 2E
MedGen UID:
1794180
Concept ID:
C5561970
Disease or Syndrome
CMD2E is characterized by neonatal or early childhood onset of dilated cardiomyopathy, with rapid progression to cardiac failure and death unless patients undergo cardiac transplantation (Vasilescu et al., 2018; Jones et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see 115200.

Professional guidelines

PubMed

Konstantinov IE, Chai P, Bacha E, Caldarone CA, Da Silva JP, Da Fonseca Da Silva L, Dearani J, Hornberger L, Knott-Craig C, Del Nido P, Qureshi M, Sarris G, Starnes V, Tsang V
J Thorac Cardiovasc Surg 2024 Aug;168(2):311-324. Epub 2024 Apr 27 doi: 10.1016/j.jtcvs.2024.04.018. PMID: 38685467
Marelli A, Beauchesne L, Colman J, Ducas R, Grewal J, Keir M, Khairy P, Oechslin E, Therrien J, Vonder Muhll IF, Wald RM, Silversides C, Barron DJ, Benson L, Bernier PL, Horlick E, Ibrahim R, Martucci G, Nair K, Poirier NC, Ross HJ, Baumgartner H, Daniels CJ, Gurvitz M, Roos-Hesselink JW, Kovacs AH, McLeod CJ, Mulder BJ, Warnes CA, Webb GD
Can J Cardiol 2022 Jul;38(7):862-896. Epub 2022 Apr 20 doi: 10.1016/j.cjca.2022.03.021. PMID: 35460862
Taylor JT, Chidsey G, Disalvo TG, Byrne JG, Maltais S
Cardiol Rev 2013 Jul-Aug;21(4):174-83. doi: 10.1097/CRD.0b013e3182880751. PMID: 23422019

Recent clinical studies

Etiology

Konstantinov IE, Chai P, Bacha E, Caldarone CA, Da Silva JP, Da Fonseca Da Silva L, Dearani J, Hornberger L, Knott-Craig C, Del Nido P, Qureshi M, Sarris G, Starnes V, Tsang V
J Thorac Cardiovasc Surg 2024 Aug;168(2):311-324. Epub 2024 Apr 27 doi: 10.1016/j.jtcvs.2024.04.018. PMID: 38685467
Pasqualin G, Boccellino A, Chessa M, Ciconte G, Marcolin C, Micaglio E, Pappone C, Sturla F, Giamberti A
Heart 2024 Jan 29;110(4):235-244. doi: 10.1136/heartjnl-2023-322420. PMID: 37487694Free PMC Article
Ramcharan TKW, Goff DA, Greenleaf CE, Shebani SO, Salazar JD, Corno AF
Pediatr Cardiol 2022 Oct;43(7):1409-1428. Epub 2022 Apr 23 doi: 10.1007/s00246-022-02908-x. PMID: 35460366
Sherwin ED, Abrams DJ
Card Electrophysiol Clin 2017 Jun;9(2):245-254. doi: 10.1016/j.ccep.2017.02.007. PMID: 28457239
Barra SN, Providência R, Paiva L, Nascimento J, Marques AL
Pacing Clin Electrophysiol 2012 Nov;35(11):1395-405. Epub 2012 Aug 16 doi: 10.1111/j.1540-8159.2012.03489.x. PMID: 22897386

Diagnosis

Alsaied T, Christopher AB, Da Silva J, Gupta A, Morell VO, Lanford L, Weinberg JG, Feingold B, Seery T, Hoskoppal A, Goldstein BH, Johnson JA, Olivieri LJ, De Fonseca Da Silva L
Pediatr Cardiol 2023 Jan;44(1):15-23. Epub 2022 Sep 23 doi: 10.1007/s00246-022-03011-x. PMID: 36151322
He BJ, Merriman AF, Cakulev I, Stambler BS, Srivastava D, Scheinman MM
JACC Clin Electrophysiol 2021 Sep;7(9):1198-1206. Epub 2021 Aug 25 doi: 10.1016/j.jacep.2021.05.008. PMID: 34454887
Qureshi MY, O'Leary PW, Connolly HM
Trends Cardiovasc Med 2018 Aug;28(6):403-409. Epub 2018 Jan 12 doi: 10.1016/j.tcm.2018.01.002. PMID: 29409687
Galea J, Ellul S, Schembri A, Schembri-Wismayer P, Calleja-Agius J
Neonatal Netw 2014 Sep-Oct;33(5):268-74. doi: 10.1891/0730-0832.33.5.268. PMID: 25161135
Geerdink LM, Kapusta L
Cardiol Young 2014 Apr;24(2):191-200. Epub 2013 Oct 29 doi: 10.1017/S1047951113001169. PMID: 24169373

Therapy

Konstantinov IE, Chai P, Bacha E, Caldarone CA, Da Silva JP, Da Fonseca Da Silva L, Dearani J, Hornberger L, Knott-Craig C, Del Nido P, Qureshi M, Sarris G, Starnes V, Tsang V
J Thorac Cardiovasc Surg 2024 Aug;168(2):311-324. Epub 2024 Apr 27 doi: 10.1016/j.jtcvs.2024.04.018. PMID: 38685467
Marelli A, Beauchesne L, Colman J, Ducas R, Grewal J, Keir M, Khairy P, Oechslin E, Therrien J, Vonder Muhll IF, Wald RM, Silversides C, Barron DJ, Benson L, Bernier PL, Horlick E, Ibrahim R, Martucci G, Nair K, Poirier NC, Ross HJ, Baumgartner H, Daniels CJ, Gurvitz M, Roos-Hesselink JW, Kovacs AH, McLeod CJ, Mulder BJ, Warnes CA, Webb GD
Can J Cardiol 2022 Jul;38(7):862-896. Epub 2022 Apr 20 doi: 10.1016/j.cjca.2022.03.021. PMID: 35460862
Holst KA, Connolly HM, Dearani JA
Methodist Debakey Cardiovasc J 2019 Apr-Jun;15(2):138-144. doi: 10.14797/mdcj-15-2-138. PMID: 31384377Free PMC Article
Kumar TKS, Boston US, Knott-Craig CJ
Semin Thorac Cardiovasc Surg 2017 Autumn;29(3):331-337. Epub 2017 Sep 25 doi: 10.1053/j.semtcvs.2017.09.006. PMID: 28958645
Atik E
Arq Bras Cardiol 2011 Nov;97(5):363-4. doi: 10.1590/s0066-782x2011001400001. PMID: 22189609

Prognosis

Wolfe SB, Reddy SCB
J Electrocardiol 2024 Sep-Oct;86:153775. Epub 2024 Aug 10 doi: 10.1016/j.jelectrocard.2024.153775. PMID: 39146690
Pasqualin G, Boccellino A, Chessa M, Ciconte G, Marcolin C, Micaglio E, Pappone C, Sturla F, Giamberti A
Heart 2024 Jan 29;110(4):235-244. doi: 10.1136/heartjnl-2023-322420. PMID: 37487694Free PMC Article
Qureshi MY, O'Leary PW, Connolly HM
Trends Cardiovasc Med 2018 Aug;28(6):403-409. Epub 2018 Jan 12 doi: 10.1016/j.tcm.2018.01.002. PMID: 29409687
Burri M, Lange R
Thorac Cardiovasc Surg 2017 Dec;65(8):639-648. Epub 2017 Aug 14 doi: 10.1055/s-0037-1604469. PMID: 28806824
Galea J, Ellul S, Schembri A, Schembri-Wismayer P, Calleja-Agius J
Neonatal Netw 2014 Sep-Oct;33(5):268-74. doi: 10.1891/0730-0832.33.5.268. PMID: 25161135

Clinical prediction guides

Wolfe SB, Reddy SCB
J Electrocardiol 2024 Sep-Oct;86:153775. Epub 2024 Aug 10 doi: 10.1016/j.jelectrocard.2024.153775. PMID: 39146690
Pasqualin G, Boccellino A, Chessa M, Ciconte G, Marcolin C, Micaglio E, Pappone C, Sturla F, Giamberti A
Heart 2024 Jan 29;110(4):235-244. doi: 10.1136/heartjnl-2023-322420. PMID: 37487694Free PMC Article
Rotar EP, Kron IL
J Card Surg 2021 Mar;36(3):1018-1019. Epub 2021 Jan 27 doi: 10.1111/jocs.15376. PMID: 33503679Free PMC Article
Holst KA, Connolly HM, Dearani JA
Methodist Debakey Cardiovasc J 2019 Apr-Jun;15(2):138-144. doi: 10.14797/mdcj-15-2-138. PMID: 31384377Free PMC Article
Qureshi MY, O'Leary PW, Connolly HM
Trends Cardiovasc Med 2018 Aug;28(6):403-409. Epub 2018 Jan 12 doi: 10.1016/j.tcm.2018.01.002. PMID: 29409687

Recent systematic reviews

van Rosendael PJ, Taha K, Guglielmo M, Teske AJ, van der Harst P, Sieswerda G, Cramer MJ, van der Zwaan HB
Eur J Clin Invest 2024 Aug;54(8):e14200. Epub 2024 Apr 1 doi: 10.1111/eci.14200. PMID: 38558254
Mustafa HJ, Aghajani F, Bairmani ZA, Khalil A
Prenat Diagn 2024 Jun;44(6-7):773-782. Epub 2023 Oct 30 doi: 10.1002/pd.6446. PMID: 37902170
Delker E, Hayes S, Kelly AE, Jones KL, Chambers C, Bandoli G
Obstet Gynecol 2023 Aug 1;142(2):269-283. Epub 2023 Jul 5 doi: 10.1097/AOG.0000000000005252. PMID: 37473409
Kayvanpour E, Sedaghat-Hamedani F, Gi WT, Tugrul OF, Amr A, Haas J, Zhu F, Ehlermann P, Uhlmann L, Katus HA, Meder B
Clin Res Cardiol 2019 Nov;108(11):1297-1308. Epub 2019 Apr 12 doi: 10.1007/s00392-019-01465-3. PMID: 30980206
Negoi RI, Ispas AT, Ghiorghiu I, Filipoiu F, Negoi I, Hostiuc M, Hostiuc S, Ginghina C
J Card Surg 2013 Jan;28(1):70-81. doi: 10.1111/jocs.12032. PMID: 23330581

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