Register or Submit a manuscript.
Quick Link
OBM Genetics

(ISSN 2577-5790)

OBM Genetics is an international Open Access journal published quarterly online by LIDSEN Publishing Inc. It accepts papers addressing basic and medical aspects of genetics and epigenetics and also ethical, legal and social issues. Coverage includes clinical, developmental, diagnostic, evolutionary, genomic, mitochondrial, molecular, oncological, population and reproductive aspects. It publishes a variety of article types (Original Research, Review, Communication, Opinion, Comment, Conference Report, Technical Note, Book Review, etc.). There is no restriction on the length of the papers and we encourage scientists to publish their results in as much detail as possible.

Publication Speed (median values for papers published in 2024): Submission to First Decision: 6.4 weeks; Submission to Acceptance: 12.2 weeks; Acceptance to Publication: 7 days (1-2 days of FREE language polishing included)

Current Issue: 2025  Archive: 2024 2023 2022 2021 2020 2019 2018 2017
Open Access Review

Etiopathogenesis of Ebstein’s Anomaly Revisited

Laxminarayan Sahoo 1 ORCID logo, Payal Murmu 2, Mohan Krishna Ghanta 3, LVKS Bhaskar 1,* ORCID logo

  1. Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, Chhattisgarh, India

  2. Community Health Center, Badampahad, Mayurbhanj, Odisha, India

  3. Department of Pharmacology, MVJ Medical College and Research Hospital, Hoskote-562114, Karnataka, India

* Correspondence: LVKS Bhaskar ORCID logo

Academic Editor: Jaroslav Alois Hubáček

Received: June 28, 2025 | Accepted: October 22, 2025 | Published: October 30, 2025

OBM Genetics 2025, Volume 9, Issue 4, doi:10.21926/obm.genet.2504314

Recommended citation: Sahoo L, Murmu P, Ghanta MK, Bhaskar L. Etiopathogenesis of Ebstein’s Anomaly Revisited. OBM Genetics 2025; 9(4): 314; doi:10.21926/obm.genet.2504314.

© 2025 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

Ebstein's anomaly (EA) is a rare form of congenital heart disease (CHD), characterized by abnormal cardiac anatomy involving a defective tricuspid valve (TV), resulting in tricuspid regurgitation (TR) and cyanosis. EA is represented in different case scenarios with varying degrees of complexity across various age groups. It usually affects 0.2-0.7 out of 10,000 live births and accounts for 0.3%-0.6% of all CHD cases. While its occurrence is mainly sporadic, evidence from multiple studies suggests that EA can be associated with genetic alterations, including mutations in MYH7, SCN5A, TPM1, NKX2-5, and KLHL26, as well as large-scale deletions such as a ~403 kb intragenic deletion in the GMDS gene, which contribute to defective cardiac development. These genes are believed to play critical roles in important pathways essential for normal mammalian cardiac development. This review aims to address existing gaps in the literature by highlighting the recent genetic findings, advancements in diagnostic and prognostic approaches, management strategies, and surgical interventions from neonates to adults.

Graphical abstract

Click to view original image

Keywords

Ebstein's anomaly; congenital heart defects; tricuspid valve insufficiency; genetics; mutations

1. Introduction

Ebstein's Anomaly (EA) is a rare cyanotic congenital heart disease (CHD) characterized by aberrant inferior/apical downward migration of the tricuspid valve (TV) leaflets into the right ventricle. This unusual migration of the TV results in a portion of the right ventricle (RV) being placed above the TV, leading to atrialization of the right ventricle (ARV) [1,2]. Further, the malformation of TV results in the overflow of blood from the right ventricle (RV) into the ARV to variable degrees, leading to tricuspid regurgitation (TR) with or without stenosis [3]. As it shows tricuspid valve dysplasia, it is also categorized under valvular heart disease [4]. Ebstein's anomaly was named after Wilhelm Ebstein, who first reported this disease in 1866 in a 19-year-old patient with severe cyanosis [5]. Ebstein anomaly affects 0.2-0.7 out of 10,000 live births and 0.3%-0.6% of congenital cardiac abnormalities, with most cases being sporadic [6]. The abnormalities in embryological development of the heart are the leading cause of CHDs. Variations in the clinical complications, i.e., from severe symptoms in infants to asymptomatic in adults, make EA unique yet complex among other CHDs [7]. Modern medical approaches and increasing general health awareness are contributing to generating new data for effective management of this rare congenital heart defect. However, the existing evidence is scattered and has yet to be analyzed comprehensively. This review attempts to provide a comprehensive understanding of the anatomy, physiopathology, clinical manifestations, underlying genetic aspects, diagnosis, and treatment of Ebstein's anomaly.

2. Anatomy and Echocardiography

Extensive studies of the heart's anatomical features in EA revealed varying degrees of TV displacement toward the right ventricle (Figure 1). Displacement is categorized into grades I-III. Grade I corresponds to mild displacement and mild disease; grade II shows moderate displacement and moderate disease; and grade III exhibits severe displacement and severe disease. Thus, the degree of valve displacement correlated well with clinical severity, with greater displacement associated with more pronounced cardiac dysfunction [8]. Failure of the formation of leaflets and the tensile apparatus of the atrioventricular valves in the inner layers of the inlet zone of the ventricles was also documented in the hearts of EA [9]. Anatomical assessment of TV is primarily performed using echocardiography [10].

Click to view original image

Figure 1 Anatomy and echocardiograph of Ebstein's anomaly heart. Image adopted from Muñoz-Castellanos et al. 2007 [8]. Anatomy (left) and echocardiograph (right). RA: Right atrium; LA: Left atrium; ARV: Atrialized right ventricle; LV: Left ventricle; FRV: Functional Right Ventricle; SL: Septal leaflet; AL: Anterior Leaflet; *: Septal leaflet tethering of tricuspid valve.

3. Pathophysiology

EA causes tricuspid regurgitation (TR) and tricuspid stenosis due to the downward displacement of the tricuspid valve (TV), leading to a reduction in the size of the right ventricle (RV- hypoplasia). RV- hypoplasia, in turn, decreases the blood flow to the pulmonary artery, resulting in functional pulmonary atresia [11]. As a result of functional pulmonary atresia, the blood is shunted through the foramen ovale/atrial septal defect (ASD), leading to a cyanotic condition [12]. The severity of cyanosis is well correlated with the extent of the tricuspid valve malformation. Tricuspid atresia is commonly seen in this condition and is often associated with a significant death rate [13]. The majority of tachyarrhythmias in patients with EA are caused by accessory atrioventricular pathways (APs), typically located along the posterior and septal lines of the tricuspid valve, where the valve leaflets are most abnormal. This occurs in addition to the hemodynamic load imposed by the structural valve defect, making EA the only congenital cardiac condition with such a strong propensity to develop APs [14]. An accessory pathway on the right side of the heart represents abnormal electrical communication between the right atrium (RA) and the right ventricle (RV), commonly referred to as the bundle of Kent. In this condition, early or pre-excitation of the RV occurs as impulses from the RA reach the RV prematurely, leading to Wolff-Parkinson-White Syndrome (WPWS). This syndrome is quite often associated with EA, and the ECG findings in patients with WPWS typically show an expansive QRS complex (slurred QRS complex), a short PR interval, and delta waves, reflecting pre-excitation of the RV [15]. Mahaim accessory pathways (MAPs), which describe abnormal connections between the atrioventricular (AV) node and a distal portion of the bundle of His inserted into the RV, are also associated with EA in patients. Ueshima et al. documented a case in a 7-year-old girl with both EA and atriofascicular Mahaim pathways (AFM) [16,17].

4. Manifestations

4.1 EA in Association with Pregnancy

Pregnant women with EA generally experience a comfortable gestation; however, their children are at risk for congenital heart disease, preterm birth, and fetal loss [18]. In one reported case, a 28-year-old G2P1L1 woman at 36 weeks of gestation, presenting with a pansystolic murmur and diagnosed with H1N1 influenza, was found to have an atrialized right ventricle (ARV), consistent with a diagnosis of EA [19]. This case report suggests that Ebstein's anomaly has varying presentations and may remain asymptomatic depending on the severity of the lesion. Prenatal evaluations in such cases should include a thorough cardiac evaluation to enable early identification and management of cardiac abnormalities, thereby reducing the risk to both the mother and the child [19].

4.2 EA in Prenatal Condition

Prenatal ultrasounds can identify cardiac developmental anomalies such as interventricular septum abnormalities, pulmonary atresia, and atrial septal defects, which are often associated with EA. Severe tricuspid valve regurgitation (TVR) may contribute to these cardiac irregularities [1,7,20]. Severe forms of EA have been identified during the prenatal stage. In one study, five fetuses with prenatal diagnoses of EA were treated, and it was observed that three of them exhibited less cardiomegaly despite having the severe form of EA, compared to the other two [21]. Intensive monitoring and early multidisciplinary consultations were part of the care. In three cases, the best outcomes were observed due to the delivery of fetuses at term in a cardiac operative suite and received quick postnatal surgical interventions such as atrial reduction, extracorporeal membrane oxygenation, and tricuspid or sternum procedures [21].

4.3 EA in Neonates

Neonates with acute EA often exhibit pulmonary underdevelopment as a result of massive heart and atrial/ventricular dilatation, which impairs pulmonary growth and function. Fetal low blood oxygen levels resulting from inadequate cardiac function can restrict intrauterine development and increase the chance of death for newborns [22]. Clinical manifestations in neonates may include congestive cardiac failure, a large heart, gradual right ventricular failure, sensations from heart rhythm disorders, cyanosis, and milder symptoms, including dyspnea during exercise in older adolescents and kids [23].

4.4 EA in Adolescents and Infants

In both children and adolescents, the symptoms of an EA include exhaustion, rhythm disturbances, cyanosis, reduced tolerance to physical activity, and developing right-sided cardiac dysfunction [1]. According to long-term studies, among infants and children aged 10 and above with this cardiac abnormality, 33 (63%) children presented with a cardiac murmur, 65 (74%) neonates with cyanosis, 6 (42%) adolescents with dysrhythmias, and 10 (43%) infants with cardiac failure [24]. Ueshima et al. documented a case in a 7-year-old girl with both EA and atriofascicular Mahaim pathways (AFM) [16,17].

4.5 EA in Adults

Most individuals with a mild form of EA remain undiagnosed into adulthood due to the non-appearance of symptoms or signs until the condition progresses with age. Adults may present with moderate to severe symptoms such as trouble breathing, ailments of the skin (cyanosis, clubbing, pallor, and peripheral edema) secondary to hypoxia or heart failure, exhaustion, discomfort in the chest, dizziness, and complications associated with physical activity [25]. A recent report on a pregnant woman indicated that standard delivery is possible and pregnancy is well tolerated after tricuspid valve repair or replacement; however, the risk to both the fetus and the mother increases if not carefully addressed and monitored under the supervision of a professional cardiologist [18,19].

4.6 Non-Syndromic EA

In approximately 80% of cases, EA is primarily a non-syndromic condition, while the remaining 20% of individuals present with genetic or Mendelian disorders that have extracardiac abnormalities. Before the advent of molecular cytogenetic techniques, such differences were not apparent. According to Lupo et al., among 188 confirmed cases, 15% were classified as non-syndromic multiples, meaning they had a minimum of one severe non-cardiac defect, whereas 78% of the cases were non-syndromic isolated, meaning they had no major non-cardiac problems [26]. Another study by Digilio et al. reported that among all EA cases, 77% are non-syndromic, 5% are associated with chromosomal syndromes, 12% with monogenic syndromes, and 6% have unidentified connections with severe organ abnormalities or deformities [27].

5. Genetics Update

Ebstein's anomaly has also been reported in other genetic syndromes like Down, CHARGE, Noonan, and Cornelia de Lange. Independent studies have identified novel potential copy number variants, including an intragenic GMDS deletion on chromosome 6p25.3, and a 403 kb de novo intragenic GMDS deletion [28,29]. The GMDS gene encodes a regulatory enzyme in GDP-fucose biosynthesis and is involved in fucosylation of many proteins, like Notch1, which is crucial for normal mammalian cardiac development [30]. A genetic variant in Kelch Like Family Member 26 (KLHL26) (p.R237C), which is a part of the ubiquitin-proteasome system (UPS). This UPS is believed to be involved in ubiquitin-mediated proteolysis, which is essential during cardiac development [7,31,32]. In addition, EA is most commonly associated with mutations in the myosin heavy chain 7 (MYH7) gene. Additional genetic associations include chromosome 15q duplications, chromosome 11q rearrangements, MYH7 mutations, and NK2 Homeobox 5 (NKX2-5) mutations. These mutations are frequently linked with cardiomyopathies, atrial septal defects (ASD), and atrioventricular conduction defects [6,33,34,35]. A novel MYH7 heterozygous missense variant (NM_000257.2; c.1085T>G, p.Met362Arg) was identified in a male patient along with his sister, both presenting with familial Ebstein's anomaly [36]. Clinical and genetic assessment is recommended for patients with this anomaly to detect congenital cardiac defects and cardiomyopathy [37].

Ebstein's anomaly occurs sporadically, with familial transmission being rare [1]. Reports suggest that about 15-29% of EA patients are also affected by left ventricular non-compaction (LVNC), a cardiac morphology having a high risk of life-threatening conditions such as embolism and thrombosis [7]. Both EA and LVNC are linked to mutations in MYH7, TPM1, NKX2-5, and sodium voltage-gated channel alpha subunit 5 (SCN5A) genes [38,39,40,41]. Genetic anomalies like trisomy 18 and deletions in 8p23.1, 1p36, and 5q35 chromosomal regions observed in both EA and LVNC support the presence of shared developmental pathways. Further, a de novo mutation in the alpha-tropomyosin gene (TPM1) has been identified in EA patients with LVNC [39,42]. This mutation results in the substitution of a highly conserved residue, Asp159Asn, caused by the c.475G>A variant, which is predicted to be detrimental to protein structure and function [42]. Among the chromosomal aberrations associated with EA, 8p23.1 and 1p36 deletions are recognized as major contributors [43]. Recent studies have demonstrated that dysregulation of microRNAs (miRNAs) and mRNA transcripts occurs in the peripheral blood of patients with Ebstein's Anomaly (EA) compared to healthy controls. Microarray profiling and differential abundance analysis of miRNAs and mRNA transcripts in EA patients and healthy controls revealed substantial alterations in 181 miRNAs and 64 transcripts [44]. Recent advancements in genetic screening and profiling techniques may reveal the complex genetic factors underlying EA. Table 1 presents the genetic alterations associated with EA, with or without related syndromes, along with their cytogenetic locations, implicated genes, and mutation types.

Table 1 Genetic alterations identified in EA with or without associated syndromes.

6. Diagnostic Procedures

Imaging procedures like echocardiography, electrocardiography (ECG), chest X-ray, cardiac magnetic resonance imaging (MRI), and computed tomography (CT) scan can be utilized to detect EA. Chest X-ray may reveal structural changes; echocardiography provides detailed visualization of the tricuspid valve; an ECG shows irregularities in cardiac rhythm; and a CT scan offers ultra-high-resolution anatomical imaging [70].

When echocardiography data are unclear or inconsistent, cardiac computed tomography (CT) ventricular volumetry can be used to evaluate the degree of EA in a subset of patients. In infants with EA, three-dimensional cardiac CT and threshold-based separation can measure volumetric severity characteristics; however, their clinically complementary role is yet to be established [71]. For the assessment of systolic and diastolic ventricular function, right atrial size, and EA-related heart architecture, MRI is recommended. MRI can accurately assess disease severity and calculate atrial-to-ventricular volume ratios. MRI is generally performed in young or neonatal patients [72].

Two-dimensional (2D) imaging is commonly used to diagnose EA; however, 3D echocardiography is often preferred due to its superior utility in visualizing ventricular architecture, subvalvular apparatus, chamber volume and function, septal anomalies, and leaflet delamination [73]. Cardiac Magnetic Resonance (CMR) imaging is considered the gold standard for assessing cardiac features in EA, offering greater accuracy than conventional echocardiography. However, the use of CMR is limited, particularly in pediatric patients, due to the need for anesthesia and its relatively high cost [10].

7. Treatment and Management

7.1 Management of EA in Neonates

Newborns presenting with symptoms of EA have a substantial postoperative death rate (28.3% i.e. 44 of 155) and difficulties keeping a sufficient cardiac function, making medical treatment difficult. Severe tricuspid regurgitation (TR), combined with elevated bronchial over-circulation and regurgitation, may compromise postpartum cardiac performance [74]. Current treatment strategies for neonates with EA include surgical intervention and invasive catheterization to manage pulmonary circulation and heart failure [75]. While unstable infants require breathing through intubation and mechanical ventilation, stable newborns may only need supplemental oxygen and prostaglandin E1 (PGE1) administration. The goals of medical therapy are to preserve ductal integrity, enhance peripheral vascular resistance (PVR), and sustain antegrade alveolar circulation [76].

7.2 Management of EA in Children and Adults

A comprehensive examination of cardiac rhythm, physical examination, and the administration of standard heart failure medications should be included in the screening process for patients diagnosed with atrial cardiac arrhythmias. It is advised that each patient receive personalized medical attention and adhere to fitness guidelines; individuals with mild EA are generally not restricted from participating in sports. Although Nesiritide reduces symptomatic recurrences of congestive heart failure and prevents repeated hospitalization in an older man with Ebstein's anomaly, it is currently not used due to limited efficacy and safety [77]. Common medications prescribed for patients with EA include Lanoxin/Digoxin tablets, tablets Amifru/Tide, LASIX injection, and occasionally potassium chloride (KCl) syrup. Patients are generally advised to avoid strenuous activities and follow a salt-restricted diet (4 grams salt/day) [78].

7.3 Surgical Interventions

The first classification system for EA was proposed by Carpentier in 1988, based on anatomical features and the functional right ventricle (FRV). The classification includes four types: type A, type B, type C and type D, which corresponds to adequate FRV, small FRV, very small FRV and tricuspid sac, respectively [2]. The most common surgical treatment for this condition is tricuspid valve repair. Restoration of a defective right-sided heart valve is generally achieved through a combination of surgical techniques, including leaflet augmentation, suture augmentation, neochordae implantation, annuloplasty band placement, and bidirectional cavopulmonary shunt [79,80].

Individuals with EA generally have low rates of premature death and often experience favorable outcomes following corrective surgical procedures. The clinical status of the individual at the time of surgery is the primary determinant of both prolonged freedom from reoperation and excellent long-term survival [81]. Based on the condition of the right ventricle (RV) and severity of EA, treatment options include biventricular restoration, one-and-a-half-ventricle reconstruction, or univentricular palliative care. Additional surgical techniques may involve defect revision, judicious plication, and structural reconstruction [82]. To reduce peripheral vascular resistance (PVR), recommended interventions include ventilatory adjustments, inhaled nitric oxide (NO), and administration of inotropic agents such as calcium, adrenaline, and milrinone [37].

8. Prognosis

Five frequently gathered clinical parameters are included in the prolonged mechanical ventilation (PMV) nomogram, which is relatively straightforward to collect and provides a simple method for predicting the likelihood of PMV following EA surgery. This nomogram can assist clinicians in assessing adolescents' vulnerability to PMV after surgical correction of EA, thereby supporting more informed surgical and treatment choices, minimizing associated negative results, allocating healthcare resources optimally, and reducing healthcare costs [83].

According to a large dataset of juvenile EA patients across Europe, 18% of diagnoses were made during young adulthood or adolescence [84]. While individuals with mild structural defects may remain asymptomatic for many years, the majority of these individuals encounter late arrhythmias at a pace similar to those with cases that are more severe presentations [85]. In children and adolescents with uncorrected EA, the study investigated the prognostic significance of atrial and ventricular myocardial deformation properties and identified distinct markers of disease progression [86]. Several lines of research indicate that hepatorenal malfunction among individuals with inborn cardiac disease is linked to right atrium (RA) malfunction, elevated RA pressure, and decreased stroke volume. These findings provide critical hemodynamic indicators for identifying individuals at risk of hepatorenal impairment and mortality, thereby facilitating timely evaluation for tricuspid valve repair or cardiac transplantation. Patients who failed to show improvement were at increased risk, whereas those who demonstrated recovery were associated with better postoperative outcomes, as measured by the hepatorenal function index [87].

9. Conclusions

Ebstein's Anomaly exhibits a broad clinical and genetic spectrum, with many unknown factors contributing to its prevalence. About 10–15% of EA cases are presented with genetic mutations, and consequently, in nearly 85–90% do not show pathogenic mutations indicating that the genetic contribution is limited Advancements in genetic tools and techniques have enabled the detection of a ~403 kb intragenic deletion in the gene encoding GMDS, identified as a potential cause for Ebstein's anomaly [28]. Transcriptomic analyses have revealed significant differences in cardiac morphogenesis between EA patients and healthy individuals, with microarray profiling identifying alterations in approximately 181 miRNAs and 64 mRNA transcripts [44]. Ebstein's anomaly is also associated with genetic syndromes such as Down syndrome, Noonan syndrome, Cornelia de Lange syndrome, and CHARGE syndrome. Mutations in genes such as MYH7, NKX2-5, SCN5A, TPM1, NONO, LAMA3, FLNA, BMPR1A, and KLHL26 have been implicated in the pathogenesis of this disease. Familial inheritance of EA is rarely reported because most mutations arise de novo, with reduced penetrance and variable expressivity. Notably, 15–29% of individuals with EA have also been diagnosed with LVNC, which elevates the risk of embolism and thrombosis [6,7,36,37]. Additionally, delta waves on ECG are common in EA due to its frequent association with WPWS [15].

Heart Ultrasound enables early diagnosis of prenatal EA. In neonates, a large heart and atrial/ventricular dilation indicate severe forms [1,7,20,22]. Cardiac murmur is present in 66% of adolescents [24]. Tricuspid atresia in EA is linked with high mortality, and tricuspid stenosis is frequently reported in affected individuals [13]. Advanced diagnostics, including 3D cardiac CT, MRI, and traditional imaging tools, enhance assessment and management of the condition [70,71,72,73]. Supplementary oxygen and PGE1 injections effectively improve pulmonary vascular resistance in newborns with mild EA. Adults are managed with salt-restricted diets and anti-arrhythmic drugs, including LASIX and Digoxin. Although the hepatorenal link remains unclear, advancements in surgical techniques and valve reconstruction have significantly improved long-term outcomes and life expectancy in patients with EA [1,37,74,75,76,78,79,80,81,82,88].

Finally, we conclude that key aspects of EA pathogenesis require further investigation, especially at the molecular level, as the precise onset of this defect remains unclear. Despite existing knowledge gaps, ongoing research is expected to yield further evidence, advancing our understanding of this rare and life-threatening anomaly.

Acknowledgments

LS. acknowledges the Council of Scientific and Industrial Research, NEW DELHI for financial support (JRF-NET2025/17845).

Author Contributions

The authors confirm their contribution to the paper as follows: Study conception and design: LVKSB. Draft manuscript: LS, PM, GMK, LVKSB. All authors reviewed the results and approved the final version of the manuscript.

Competing Interests

All authors declare that there is no conflict of interests.

References

  1. Attenhofer Jost CH, Connolly HM, Dearani JA, Edwards WD, Danielson GK. Ebstein's anomaly. Circulation. 2007; 115: 277-285. [CrossRef] [Google scholar]
  2. Carpentier A, Chauvaud S, Macé L, Relland J, Mihaileanu S, Marino JP, et al. A new reconstructive operation for Ebstein's anomaly of the tricuspid valve. J Thorac Cardiovasc Surg. 1988; 96: 92-101. [CrossRef] [Google scholar]
  3. Schultz AH, Kreutzer J. Chapter 3—Cyanotic heart disease. In: Pediatric cardiology. Philadelphia, PA: Mosby Elsevier; 2006. pp. 51-78. [CrossRef] [Google scholar]
  4. Shanmugam S, Sennaiyan UN, Krishna MR. Tricuspid valve dysplasia at fetal autopsy. Fetal Pediatr Pathol. 2022; 41: 529-532. [CrossRef] [Google scholar] [PubMed]
  5. Ebstein W. Ueber einen sehr seltenen Fall von Insufficienz der Valvula tricuspidalis, bedingt durch eine angeborene hochgradige Missbildung derselben. In: Archiv für Anatomie, Physiologie und wissenschaftliche Medicin. BIU Santé; 1866. pp. 238-254. [Google scholar]
  6. Singh DP, Hussain K, Horenstein MS, Mahajan K. Ebstein anomaly and malformation. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2025. [Google scholar]
  7. Farhan M, Prajjwal P, Sai VP, Aubourg O, Ushasree T, Sanga HS, et al. Neurological, extracardiac, and cardiac manifestations of Ebstein's anomaly along with its genetics, diagnostic techniques, treatment updates, and the future ahead. Cureus. 2023; 15: e35115. [CrossRef] [Google scholar]
  8. Muñoz-Castellanos L, Espinola-Zavaleta N, Kuri-Nivón M, Keirns C. Ebstein's Anomaly: Anatomo-echocardiographic correlation. Cardiovasc Ultrasound. 2007; 5: 43. [CrossRef] [Google scholar] [PubMed]
  9. Anderson KR, Zuberbuhler JR, Anderson RH, Becker AE, Lie JT. Morphologic spectrum of Ebstein's anomaly of the heart: A review. Mayo Clin Proc. 1979; 54: 174-180. [Google scholar]
  10. Qureshi MY, Dearani JA. Commentary: Gold or silver? Value of cardiac magnetic resonance imaging over echocardiography in Ebstein's anomaly. J Thorac Cardiovasc Surg. 2021; 161: 1109-1110. [CrossRef] [Google scholar] [PubMed]
  11. Lin JH, Da Silva J, Da Fonseca Da Silva L, Devine W, Yeh J, Alsaied T. Chapter 8—Ebstein's Anomaly. In: Congenital heart defects–Recent advances. Rijeka, Croatia: IntechOpen; 2022. pp. 139-174. [CrossRef] [Google scholar]
  12. Kumar TS. Ebstein's anomaly in the neonate. Indian J Thorac Cardiovasc Surg. 2021; 37: 17-25. [CrossRef] [Google scholar] [PubMed]
  13. Minocha PK, Horenstein MS, Phoon C. Tricuspid atresia. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2025. [Google scholar]
  14. Walsh EP. Ebstein's anomaly of the tricuspid valve: A natural laboratory for re-entrant tachycardias. JACC Clin Electrophysiol. 2018; 4: 1271-1288. [CrossRef] [Google scholar] [PubMed]
  15. Chhabra L, Goyal A, Benham MD. Wolff-Parkinson-White Syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2025. [Google scholar]
  16. Pérez-Riera AR, Barbosa-Barros R, Daminello-Raimundo R, de Abreu LC, Nikus K. Electro-vectorcardiographic and electrophysiological aspects of Ebstein's anomaly. Ann Noninvasive Electrocardiol. 2019; 24: e12590. [CrossRef] [Google scholar] [PubMed]
  17. Ueshima K, Nakamura Y, Takeno S, Miyake T, Takemura T. Atriofascicular Mahaim with Ebstein anomaly: A case report. J Arrhythmia. 2017; 33: 508-510. [CrossRef] [Google scholar] [PubMed]
  18. Connolly HM, Warnes CA. Ebstein's anomaly: Outcome of pregnancy. J Am Coll Cardiol. 1994; 23: 1194-1198. [CrossRef] [Google scholar] [PubMed]
  19. Shah A, Diwan A. An unexpected discovery in pregnancy: A case report. J Med Sci. 2024; 10: 235-238. [CrossRef] [Google scholar]
  20. Melendres G, Ormsby EL, McGahan JP, Moon-Grady AJ, Towner D, Taylor D. Prenatal diagnosis of Ebstein anomaly: A potential pitfall. J Ultrasound Med. 2004; 23: 551-555. [CrossRef] [Google scholar] [PubMed]
  21. Narang K, Wyatt M, O'Leary P, Qureshi MY, Kolbe A, Stephens EH, et al. Novel approach to prenatal predictors of outcomes for fetuses with severe Ebstein anomaly. J Matern Fetal Neonatal Med. 2023; 36: 2271626. [CrossRef] [Google scholar] [PubMed]
  22. Ramcharan TK, Goff DA, Greenleaf CE, Shebani SO, Salazar JD, Corno AF. Ebstein's anomaly: From fetus to adult—literature review and pathway for patient care. Pediatr Cardiol. 2022; 43: 1409-1428. [CrossRef] [Google scholar] [PubMed]
  23. Oxenius A, Jost CH, Prêtre R, Dave H, Bauersfeld U, Kretschmar O, et al. Management and outcome of Ebstein's anomaly in children. Cardiol Young. 2013; 23: 27-34. [CrossRef] [Google scholar] [PubMed]
  24. Celermajer DS, Bull C, Till JA, Cullen S, Vassillikos VP, Sullivan ID, et al. Ebstein's anomaly: Presentation and outcome from fetus to adult. J Am Coll Cardiol. 1994; 23: 170-176. [CrossRef] [Google scholar] [PubMed]
  25. Gupta S, Naik R, Hafiz M, Choudhary N. Case report: An uncommon association of Ebstein's anomaly and rheumatic mitral stenosis. IHJ Cardiovasc Case Rep. 2020; 4: 41-44. [CrossRef] [Google scholar]
  26. Lupo PJ, Langlois PH, Mitchell LE. Epidemiology of Ebstein anomaly: Prevalence and patterns in Texas, 1999–2005. Am J Med Genet A. 2011; 155: 1007-1014. [CrossRef] [Google scholar] [PubMed]
  27. Digilio MC, Silvestri LM, Dallapiccola B, Marino B. Genetics of Ebstein anomaly. In: The tricuspid valve in congenital heart disease. Milano, Italy: Springer Milan; 2014. pp. 25-30. [CrossRef] [Google scholar]
  28. Lo-A-Njoe SM, Verberne EA, van der Veken LT, Arends E, van Tintelen JP, Postma AV, et al. GMDS intragenic deletions associate with congenital heart disease including Ebstein anomaly. Cardiogenetics. 2023; 13: 106-112. [CrossRef] [Google scholar]
  29. Sicko RJ, Browne ML, Rigler SL, Druschel CM, Liu G, Fan R, et al. Genetic variants in isolated Ebstein anomaly implicated in myocardial development pathways. PLoS One. 2016; 11: e0165174. [CrossRef] [Google scholar] [PubMed]
  30. MacGrogan D, Luna-Zurita L, de la Pompa JL. Notch signaling in cardiac valve development and disease. Birth Defects Res A Clin Mol Teratol. 2011; 91: 449-459. [CrossRef] [Google scholar] [PubMed]
  31. Samudrala SS, North LM, Stamm KD, Earing MG, Frommelt MA, Willes R, et al. Novel KLHL26 variant associated with a familial case of Ebstein's anomaly and left ventricular noncompaction. Mol Genet Genom Med. 2020; 8: e1152. [CrossRef] [Google scholar] [PubMed]
  32. Thareja SK, Anfinson M, Cavanaugh M, Kim MS, Lamberton P, Radandt J, et al. Altered contractility, Ca2+ transients, and cell morphology seen in a patient-specific iPSC-CM model of Ebstein's anomaly with left ventricular noncompaction. Am J Physiol Heart Circ Physiol. 2023; 325: H149-H162. [CrossRef] [Google scholar] [PubMed]
  33. Benson DW, Silberbach GM, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Investig. 1999; 104: 1567-1573. [CrossRef] [Google scholar] [PubMed]
  34. de Lonlay‐Debeney P, de Blois MC, Bonnet D, Amiel J, Abadie V, Picq M, et al. Ebstein anomaly associated with rearrangements of chromosomal region 11q. Am J Med Genet. 1998; 80: 157-159. [CrossRef] [Google scholar]
  35. Miller MS, Rao PN, Dudovitz RN, Falk RE. Ebstein anomaly and duplication of the distal arm of chromosome 15: Report of two patients. Am J Med Genet A. 2005; 139: 141-145. [CrossRef] [Google scholar] [PubMed]
  36. Hirono K, Hata Y, Ibuki K, Yoshimura N. Familial Ebstein's anomaly, left ventricular noncompaction, and ventricular septal defect associated with an MYH7 mutation. J Thorac Cardiovasc Surg. 2014; 148: e223-e226. [CrossRef] [Google scholar] [PubMed]
  37. Postma AV, Van Engelen K, Van De Meerakker J, Rahman T, Probst S, Baars MJ, et al. Mutations in the sarcomere gene MYH7 in Ebstein anomaly. Circ Cardiovasc Genet. 2011; 4: 43-50. [CrossRef] [Google scholar] [PubMed]
  38. Vermeer AM, Van Engelen K, Postma AV, Baars MJ, Christiaans I, De Haij S, et al. Ebstein anomaly associated with left ventricular noncompaction: An autosomal dominant condition that can be caused by mutations in MYH7. Am J Med Genet C Semin Med Genet. 2013; 163: 178-184. [CrossRef] [Google scholar] [PubMed]
  39. Nijak A, Alaerts M, Kuiperi C, Corveleyn A, Suys B, Paelinck B, et al. Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation. Eur J Med Genet. 2018; 61: 8-10. [CrossRef] [Google scholar] [PubMed]
  40. Dixit R, Narasimhan C, Balekundri VI, Agrawal D, Kumar A, Mohapatra B. Functional analysis of novel genetic variants of NKX2-5 associated with nonsyndromic congenital heart disease. Am J Med Genet A. 2021; 185: 3644-3663. [CrossRef] [Google scholar] [PubMed]
  41. Neu A, Eiselt M, Paul M, Sauter K, Stallmeyer B, Isbrandt D, et al. A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease. Hum Mutat. 2010; 31: E1609-E1621. [CrossRef] [Google scholar] [PubMed]
  42. Kelle AM, Bentley SJ, Rohena LO, Cabalka AK, Olson TM. Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation. Am J Med Genet A. 2016; 170: 2186-2190. [CrossRef] [Google scholar] [PubMed]
  43. Digilio MC, Bernardini L, Lepri F, Giuffrida MG, Guida V, Baban A, et al. Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1. Am J Med Genet A. 2011; 155: 2196-2202. [CrossRef] [Google scholar] [PubMed]
  44. Abu-Halima M, Wagner V, Becker LS, Ayesh BM, Abd El-Rahman M, Fischer U, et al. Integrated microRNA and mRNA expression profiling identifies novel targets and networks associated with Ebstein's anomaly. Cells. 2021; 10: 1066. [CrossRef] [Google scholar] [PubMed]
  45. Faivre L, Morichon-Delvallez N, Viot G, Martinovic J, Pinson MP, Aubry JP, et al. Prenatal detection of a 1p36 deletion in a fetus with multiple malformations and a review of the literature. Prenat Diagn. 1999; 19: 49-53. [CrossRef] [Google scholar]
  46. Riegel M, Castellan C, Balmer D, Brecevic L, Schinzel A. Terminal deletion, del (1)(p36. 3), detected through screening for terminal deletions in patients with unclassified malformation syndromes. Am J Med Genet. 1999; 82: 249-253. [CrossRef] [Google scholar]
  47. Battaglia A, Hoyme HE, Dallapiccola B, Zackai E, Hudgins L, McDonald-McGinn D, et al. Further delineation of deletion 1p36 syndrome in 60 patients: A recognizable phenotype and common cause of developmental delay and mental retardation. Pediatrics. 2008; 121: 404-410. [CrossRef] [Google scholar] [PubMed]
  48. Bækvad-Hansen M, Tümer Z, Delicado A, Erdogan F, Tommerup N, Larsen LA. Delineation of a 2.2 Mb microdeletion at 5q35 associated with microcephaly and congenital heart disease. Am J Med Genet A. 2006; 140: 427-433. [CrossRef] [Google scholar] [PubMed]
  49. Correa-Villaseñor A, Ferencz C, Neill CA, David Wilson P, Boughman JA. Ebstein's malformation of the tricuspid valve: Genetic and environmental factors. Teratology. 1994; 50: 137-147. [CrossRef] [Google scholar] [PubMed]
  50. Johnson CD, Ortiz-Colom PM, Sainz de la PeÑa H, Barroso E. Ebstein's anomaly in a patient with Down's syndrome. Bol Asoc Med Puerto Rico. 1989; 81: 221-222. [Google scholar]
  51. Leite MD, Gianisella RB, Zielinsky P. Intrauterine detection of Ebstein's anomaly and Down's syndrome: Prenatal diagnosis of a rare combination. Arq Bras Cardiol. 2004; 82: 390-392. [CrossRef] [Google scholar] [PubMed]
  52. Tanasan A, Rostampour F, Sanginabadi M, Falahi A. Down syndrome associated with Epstein's anomaly and pulmonary hypertension in a 2.5 months infant: A case report study. J Emerg Health Care. 2015; 4: 187-190. [Google scholar]
  53. Venturini E, Musaio L, Strazzeri R, Baroni F. Ebstein's tricuspid anomaly and Down's syndrome. A clinical case report. Recenti Prog Med. 1992; 83: 556-558. [Google scholar]
  54. Silva SR, Bruner JP, Moore CA. Prenatal diagnosis of Down's syndrome in the presence of isolated Ebstein's anomaly. Fetal Diagn Ther. 1999; 14: 149-151. [CrossRef] [Google scholar] [PubMed]
  55. Cyrus C, Cyril E, Cherian KM, Kulkarni S, Nallathambi C. Down syndrome with tandem 21; 21 rearrangement and Ebstein's anomaly—A case report. Int J Cardiol. 2007; 115: E58-E60. [CrossRef] [Google scholar] [PubMed]
  56. Upadhyay S, Law S, Kholwadwala D. A newborn with cardiomegaly. J Emerg Trauma Shock. 2010; 3: 298. [CrossRef] [Google scholar] [PubMed]
  57. Pepeta L, Clur SA. Ebstein's anomaly and Down's syndrome. Cardiovasc J Afr. 2013; 24: 382-384. [CrossRef] [Google scholar] [PubMed]
  58. Bauk L, Espinola-Zavaleta N, Muñoz-Castellanos L. Ebstein's malformation in the setting of Down's syndrome. Cardiol Young. 2003; 13: 370-372. [CrossRef] [Google scholar]
  59. Siehr SL, Punn R, Priest JR, Lowenthal A. Ebstein anomaly and Trisomy 21: A rare association. Ann Pediatr Cardiol. 2014; 7: 67-69. [CrossRef] [Google scholar] [PubMed]
  60. Yuan SM. Ebstein's anomaly: Genetics, clinical manifestations, and management. Pediatr Neonatol. 2017; 58: 211-215. [CrossRef] [Google scholar] [PubMed]
  61. O'Connor R, Al-Murrani A, Aftimos S, Asquith P, Mazzaschi R, Eyrolle-Guignot D, et al. Pure duplication of the distal long arm of chromosome 15 with Ebstein anomaly and clavicular anomaly. Case Rep Genet. 2011; 2011: 898706. [CrossRef] [Google scholar] [PubMed]
  62. Mattia D, Lindblade C, Oatman O, Prakash S, Grebe T. Novel case of Prader–Willi Syndrome and Ebstein's anomaly: Implications for complex care management. J Pediatr Genet. 2024; 13: 315-319. [CrossRef] [Google scholar] [PubMed]
  63. Giannakou A, Sicko RJ, Zhang W, Romitti P, Browne ML, Caggana M, et al. Copy number variants in Ebstein anomaly. PLoS One. 2017; 12: e0188168. [CrossRef] [Google scholar] [PubMed]
  64. Giuffrida MG, Goldoni M, Genovesi ML, Carpentieri G, Torres B, Deac AD, et al. 3' UTR Deletion of NONO leads to corpus callosum anomaly, left ventricular non-compaction and Ebstein's anomaly in a male fetus. Diagnostics. 2022; 12: 2354. [CrossRef] [Google scholar] [PubMed]
  65. Budde BS, Binner P, Waldmüller S, Höhne W, Blankenfeldt W, Hassfeld S, et al. Noncompaction of the ventricular myocardium is associated with a de novo mutation in the β-myosin heavy chain gene. PloS One. 2007; 2: e1362. [CrossRef] [Google scholar] [PubMed]
  66. Gioli-Pereira L, Pereira AC, Mesquita SM, Xavier-Neto J, Lopes AA, Krieger JE. NKX2.5 mutations in patients with non-syndromic congenital heart disease. Int J Cardiol. 2010; 138: 261-265. [CrossRef] [Google scholar] [PubMed]
  67. Zhou Z, Huang X, Tang X, Chen W, Chen Q, Zhang C, et al. Heterozygous nonsense variants in laminin subunit 3α resulting in Ebstein's anomaly. Hum Genet Genom Adv. 2023; 4: 100227. [CrossRef] [Google scholar] [PubMed]
  68. Mercer CL, Andreoletti G, Carroll A, Salmon AP, Temple IK, Ennis S. Familial Ebstein anomaly: Whole exome sequencing identifies novel phenotype associated with FLNA. Circ Cardiovasc Genet. 2017; 10: e001683. [CrossRef] [Google scholar] [PubMed]
  69. Demal TJ, Heise M, Reiz B, Dogra D, Brænne I, Reichenspurner H, et al. A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A. Sci Rep. 2019; 9: 2959. [CrossRef] [Google scholar] [PubMed]
  70. Dalakoti M, Singh D, Yeo WT, Tay LW, Poh KK. Electrocardiography findings and clinical presentation in Ebstein's anomaly. Singap Med J. 2019; 60: 560-564. [CrossRef] [Google scholar] [PubMed]
  71. Goo HW, Park SH. Complimentary cardiac computed tomography ventricular volumetry-derived metrics of severity in patients with Ebstein anomaly: Comparison with echocardiography-based severity indices. Pediatr Cardiol. 2024; 45: 24-31. [CrossRef] [Google scholar] [PubMed]
  72. Yalonetsky S, Tobler D, Greutmann M, Crean AM, Wintersperger BJ, Nguyen ET, et al. Cardiac magnetic resonance imaging and the assessment of Ebstein anomaly in adults. Am J Cardiol. 2011; 107: 767-773. [CrossRef] [Google scholar] [PubMed]
  73. Celermajer DS, Cullen S, Sullivan ID, Spiegelhalter DJ, Wyse RK, Deanfield JE. Outcome in neonates with Ebstein's anomaly. J Am Coll Cardiol. 1992; 19: 1041-1046. [CrossRef] [Google scholar] [PubMed]
  74. Goldberg SP, Jones RC, Boston US, Haddad LM, Wetzel GT, Chin TK, et al. Current trends in the management of neonates with Ebstein's anomaly. World J Pediatr Congenit Heart Surg. 2011; 2: 554-557. [CrossRef] [Google scholar] [PubMed]
  75. Knott-Craig CJ, Overholt ED, Ward KE, Razook JD. Neonatal repair of Ebstein's anomaly: Indications, surgical technique, and medium-term follow-up. Ann Thorac Surg. 2000; 69: 1505-1510. [CrossRef] [Google scholar] [PubMed]
  76. Sainathan S, da Silva LD, da Silva JP. Ebstein's anomaly: Contemporary management strategies. J Thorac Dis. 2020; 12: 1161-1173. [CrossRef] [Google scholar] [PubMed]
  77. Tavakol M, Banko L, Schifter D. Use of nesiritide in Ebstein's anomaly. Int J Angiol. 2008; 17: 47-49. [CrossRef] [Google scholar] [PubMed]
  78. Lennie TA, Chung ML, Moser DK. What should we tell patients with heart failure about sodium restriction and how should we counsel them? Curr Heart Fail Rep. 2013; 10: 219-226. [CrossRef] [Google scholar] [PubMed]
  79. Hetzer R, Hacke P, Javier M, Miera O, Schmitt K, Weng Y, et al. The long-term impact of various techniques for tricuspid repair in Ebstein's anomaly. J Thorac Cardiovasc Surg. 2015; 150: 1212-1219. [CrossRef] [Google scholar] [PubMed]
  80. Holst KA, Dearani JA, Said S, Pike RB, Connolly HM, Cannon BC, et al. Improving results of surgery for Ebstein anomaly: Where are we after 235 cone repairs? Ann Thorac Surg. 2018; 105: 160-168. [CrossRef] [Google scholar] [PubMed]
  81. Badiu CC, Schreiber C, Hörer J, Ruzicka DJ, Wottke M, Cleuziou J, et al. Early timing of surgical intervention in patients with Ebstein's anomaly predicts superior long-term outcome. Eur J Cardio Thorac Surg. 2010; 37: 186-192. [CrossRef] [Google scholar] [PubMed]
  82. Silva GV, Miana LA, Caneo LF, Turquetto AL, Tanamati C, Penha JG, et al. Early and long-term outcomes of surgical treatment of Ebstein's anomaly. Braz J Cardiovasc Surg. 2019; 34: 511-516. [CrossRef] [Google scholar] [PubMed]
  83. Liu Q, Luo Q, Li Y, Wu X, Wang H, Huang J, et al. A simple-to-use nomogram for predicting prolonged mechanical ventilation for children after Ebstein anomaly corrective surgery: A retrospective cohort study. BMC Anesthesiol. 2023; 23: 24. [CrossRef] [Google scholar] [PubMed]
  84. Geerdink LM, Delhaas T, Helbing WA, du Marchie Sarvaas GJ, Ter Heide H, Rozendaal L, et al. Paediatric Ebstein's anomaly: How clinical presentation predicts mortality. Arch Dis Child. 2018; 103: 859-863. [CrossRef] [Google scholar] [PubMed]
  85. Bhupali AN, Patankar KB, Paranjpe FS, Tamhane AU. Giant right atrium in a foetus. Indian Heart J. 2013; 65: 493-495. [CrossRef] [Google scholar] [PubMed]
  86. Prota C, Di Salvo G, Sabatino J, Josen M, Paredes J, Sirico D, et al. Prognostic value of echocardiographic parameters in pediatric patients with Ebstein's anomaly. Int J Cardiol. 2019; 278: 76-83. [CrossRef] [Google scholar] [PubMed]
  87. Egbe AC, Miranda WR, Dearani J, Kamath PS, Connolly HM. Prognostic role of hepatorenal function indexes in patients with Ebstein anomaly. J Am Coll Cardiol. 2020; 76: 2968-2976. [CrossRef] [Google scholar] [PubMed]
  88. Krieger EV, Valente AM. Diagnosis and management of Ebstein anomaly of the tricuspid valve. Curr Treat Options Cardiovasc Med. 2012; 14: 594-607. [CrossRef] [Google scholar] [PubMed]
Journal Metrics
2024
CiteScore SJR SNIP
0.70.1470.167
Newsletter
Download PDF Download Full-Text XML Download Citation
0 0
Newsletter  

TOP