Ebstein malformation of the tricuspid valve (ORPHA:1880)
A rare congenital cardiac anomaly characterized by downward (apical) displacement of the functional annulus, due to incomplete delamination of the septal and inferior leaflets of the tricuspid valve such that they are hinged within the right ventricle, rather than as expected at the atrioventricular junction. The anterosuperior leaflet is often abnormal (redundancy, fenestrations, tethering with abnormal subvalvar apparatus). The atrioventricular junction and the ''atrialized'' portion of the right ventricle are dilated, with variable degrees of thinning of the right ventricular wall.
Epidemiology
The prevalence at birth is between 1/20,000-100,000. Ebstein malformation of the tricuspid valve accounts for less than 1% of all congenital heart defects. Both sexes are equally affected.
Clinical description
Clinical presentation is heterogeneous and depends on the severity of the lesion (extent of tethering of the antero-superior leaflet across the normal valvar orifice), and the degree of dysfunction of the right ventricle. Patients with minor forms of the disease remain asymptomatic or may present with an incidental murmur, exertional dyspnea, fatigue, or palpitations. Those with severe forms can present at various ages with arrhythmias, cyanosis, and sometimes cardiac failure. Those with the most severe malformations present as neonates, often with so-called ``wall-to-wall'' hearts. During adulthood, supraventricular tachycardia can also be observed, a proportion of patients also having Wolff-Parkinson-White syndrome. The malformation is often associated with other cardiac lesions, such as atrial or ventricular septal defects, patency of the arterial duct, pulmonary stenosis or atresia, or left ventricular non-compaction.
Etiology
Etiology is unknown. In some cases, maternal ingestion of lithium was associated with the disease. The incidence of heterozygous MYH7 (14q11.2) mutations is 6%, and more frequent if left ventricular non-compaction is associated.
Diagnostic methods
Diagnosis is based on cross-sectional or 3D echocardiography which also reveals the extent of valvular abnormalities (tethering and thinning) as well as the degree of regurgitation or stenosis. Presence of associated defects should also be assessed. Electrocardiogram can reveal right atrial hypertrophy, right bundle branch block, and supraventricular tachycardia. Radiography shows any cardiomegaly. Cardiac MRI shows the full extent of the valvar abnormalities, quantifies right ventricular volume, function and tricuspid regurgitation, and helps to plan surgery.
Differential diagnosis
The major differential diagnosis, particularly during fetal life, is dysplasia of the leaflets of the tricuspid valve. Both malformations can lead to severe tricuspid insufficiency. Gross thinning of the walls of the right ventricle should not be confused with Uhl anomaly. Severe forms of Ebstein malformation with an imperforate tricuspid valve must be distinguished from tricuspid atresia.
Antenatal diagnosis
Diagnosis is usually antenatal and based on severe tricuspid insufficiency with gross dilatation of the right atrium, which can cause fetal hydrops and fetal demise.
Genetic counseling
Familial cases associated with MYH7 are extremely rare; in these cases autosomal dominant transmission is reported.
Management and treatment
Medical treatment relies on inotropic agents (in case of cardiac failure) and antiarrhythmic drugs (in case of tachyarrhythmia). Definitive treatment is surgical and ideally consists of reconstructive surgery by the cone method. Provided that valvar anatomy is favorable, patients should be considered for surgery when they develop symptoms and/or worsening exercise capacity, cyanosis, paradoxical embolism, progressive right ventricle (RV) dilation or dysfunction, or arrhythmias. If the valve is too malformed, replacement with a bioprosthesis is the only option. Partial cavopulmonary connection can be used when RV function is impaired. Most arrhythmias can be treated percutaneously, and oval foramen can be closed percutaneously when responsible for cyanosis.
Prognosis
Patients with asymptomatic and mild forms have a normal life expectancy. However, symptoms usually develop progressively from adulthood onwards. Patients with severe forms of the disease, particularly those presenting during the fetal period or as neonates, have an increased risk of death due to biventricular failure, including at birth or during physical exercise. Supraventricular arrhythmias are frequent, particularly in adults, and can lead to sudden cardiac death.

                            Last update: 
                            February 2021


                            - Expert reviewer(s): 
                            Pr Lucile HOUYEL