American Journal of Medical Genetics 42:307-309 (1992)

Ebstein Anomaly: Report of a Familial Occurrence and Prenatal Diagnosis Nathalie McIntosh, David Chitayat, Marietta Bardanis, and Jean-Claude Fouron Department of Pediatrics, Division of Medical Genetics (N.M., D.C.), The Montreal Children’s Hospital; Lady Davis Znstitute for Medical Research, Departments of Biology and Pediatrics (M.B.); Center For Human Genetics, McGill University (N.M., D.C., M.B.);Department of Pediatrics, Division of Cardiology, Universitk de Montre‘al and Hepita1 Ste-Justine (J-CPJ, Montreal, Quebec, Canada The Ebstein anomaly is a rare congenital heart disease involving the position and structure of the tricuspid valve. Although most cases are sporadic, familial occurrence has been documented. We report on 2 sisters, born to consanguineous parents, who were diagnosed prenatally with severe Ebstein anomaly.

KEY WORDS: Ebstein anomaly, autosomal recessive, multifactorial, congenital heart disease, echocardiography INTRODUCTION The Ebstein anomaly is a congenital heart defect (CHD) characterized by varying degrees of downward displacement of the proximal attachments of the tricuspid valve leaflets from the atrioventricular valve ring, abnormalities of the distal attachments of the tricuspid valve, tricuspid valve dysplasia, and right ventricular dysplasia. The cause of this malformation is unknown and familial occurrence is rare. We report on 2 sisters with severe Ebstein anomaly whose parents are first cousins once removed. Both sibs were diagnosed prenatally by fetal ultrasound (U/S).

atrium, pleural effusion, and ascites suggestive of severe Ebstein anomaly. Delivery was by emergency cesarean for fetal bradycardia. Birthweight was 2,520 g (25th centile), and the Apgar scores were 1 and 4, a t 1 and 5 min, respectively. Cyanosis was noted at birth and persisted on 100%oxygen. A chest film showed maximal cardiomegaly, and a Doppler-echocardiographyshowed patent ductus arteriosus (PDA)with left to right shunt, atrial septal defect (ASD), a huge right atrium, and a downwardly displaced tricuspid valve with regurgitation consistent with Ebstein anomaly. The pulmonic valve and aortic arch were normal. At 3 days of age hematuria, hematochisia, and right pneumothorax were noted. The patient died shortly after. Autopsy showed pericardial effusion and ascites, cardiomegaly, and considerable dilatation of the right atrium with patent foramen ovale. The tricuspid valve was thick and displaced downward; the right ventricle was hypoplastic. No extracardiac malformations were noted and the chromosomes were apparently normal.

Patient 2 The second pregnancy of this couple was monitored by fetal echocardiography. At 18 weeks of gestation fetal ultrasonography reported a normal heart; however, repeat ultrasonography a t 31 weeks (Fig. 1) showed cardiomegaly, large right atrium, and downward displacement of the tricuspid valve, consistent with Ebstein anomaly. Fetal distress was noted at 32 weeks and a girl CLINICAL REPORTS was delivered by cesarean section. Apgar scores were 5 Patient 1 and 7, at 1 and 5 min, respectively. Birth weight was A girl was born to a 31-year-old gravida 1mother and 1,780 g (50th centile). Shortly after birth the patient 37-year-old father. Parents were of Sri Lankan descent developed respiratory distress and cyanosis. A chest and were first cousins once removed. Both had normal film showed marked cardiomegaly, a large right atrium, cardiologic assessment including echocardiography a very small lung field which seemed oligemic, and (done after their second pregnancy). A routine ultra- ascites. A Doppler-echocardiography done at 1 hr sound a t 38 weeks of gestation showed a large right showed situs solitusilevocardia, an enlarged right atrium, a small right ventricle, and a thickened, but patent, pulmonary valve. The tricuspid valve was thickened, with a distal insertion of the septal tricuspid leafFkceived for publication January 22, 1991; revision received let, and severe regurgitation. There was a small PDA June 3, 1991. and a perimembranous VSD, both with left to right Address reprint requests to Dr. D. Chitayat, Division of Medical shunt, and a probable secundum ASD. Genetics, The Montreal Children’s Hospital, 2300 ‘hpper St., At 35 hr she failed to respond to prostaglandin infuMontreal, Quebec, H3H 1P3, Canada. 0 1992 Wiley-Liss, Inc.

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Fig. 1. Fetal echocardiography of patient 2 at 31 weeks of gestation. Note the dilated right atrium (RA), thick tricuspid valve (TV), and hypoplastic right ventricle (RV). Left atrium, LA; mitral valve, MV; left ventricle, LV; muscle band, MB.

sion and died shortly after. The pathology report confirmed the echocardiographic findings.

DISCUSSION The Ebstein anomaly is a rare type of CHD which accounts for 0.05%of all congenital heart malformations [Siebert et al., 19891 with an incidence of 0.12/1,000 livebirths [Harper, 19881. The cause of the Ebstein anomaly is not well understood and in most cases it is thought to be a multifactorial trait. Thus, although the frequency of other CHD in first-degree relatives of Ebstein's anomaly was found to be higher than in the general population, the recurrence of Ebstein anomaly within the same family is rare [Emanuel et al., 19761. Among the nongenetic causes of Ebstein anomaly are intrauterine exposure to lithium and intrauterine infections [Siebert et al., 19891. Although rare, familial cases of Ebstein anomaly have been reported; among them were 5 cases of a parent and an offspring, and 6 sets of sibs (Table I). In one case of affected sibs the parents were first cousins. We report on a second consanguineous family with 2 offspring affected with Ebstein anomaly, thus supporting the observation that in some cases this rare CHD may be an autosomal recessive trait although multifactorial inheritance cannot be excluded. Ebstein anomaly has been diagnosed previously in utero [Allan et al., 1985; Silverman et al., 1985; Kleinman et al., 19821. The optimal age for examination is between 16 and 32 weeks of gestation, and the findings observed include a severely incompetent tricuspid valve, a severely dilated right atrium, and an atrialized ventricle [Lange et al., 19801. Using color flow Dopplerechocardiography, the severity of the tricuspid regurgitation can be demonstrated, and using continuous wave Doppler,the right ventricular pressure can be estimated [Fyfe and Kline, 19901. The prognosis of newborn infant affected with severe

form of Ebstein anomaly is usually poor. Morphological findings which correlate with early death include tethered distal attachments of the anterosuperior tricuspid leaflets, and dilated right atrium. Clinical risk factors associated with early mortality are persistent congestive heart failure, mechanical ventilation, and low birth weight for gestational age [Roberson and Silverman, 19891. There is also speculation that large pleural and pericardial effusions may contribute to pulmonary hypoplasia and, consequently, adversely affect outcome. Both of our cases showed pleural and pericardial effusions, markedly dilated right atria, and severely distally

TABLE I. Previously Reported Familial Cases of Ebstein Anomaly Reference Gueron et al. [19661 Donegan et al. [1968] Simcha and Bonham-Carter [1971] Rosenmann et al. [1976] Watson [1974]

Number of cases

Lo et al. [19791 Pierard et al. [19851 Davido et al. [1985] Zalzstein et al. [19901 Present family rig901 "Consanguineous parents.

Relationship Sister and brother" Nephew and maternal uncle Father and daughter Two brothers Father and son Two sisters Two brothers Two brothers Father and son Father and son Mother and daughter

2

Two sisters"

Ebstein Anomaly attached tricuspid leaflets; both infants needed mechanical ventilation, and died shortly after birth. Complex congenital heart anomalies which carry a poor prognosis, such as severe Ebstein anomaly, create difficult ethical problems when diagnosed in utero. Ethically relevant factors influencing management of these cases have been discussed [Veille et al., 19891, and no doubt will be the topic of ongoing discussions as more cases of congenital heart malformations are prenatally diagnosed and technological advances for their early treatment are made.

REFERENCES Allan LD, Crawford DC, Anderson RH, Tyrian M (1985): Spectrum of congenital heart disease detected echocardiographically in prenatal life. Br Heart J 54523-526. Davido A, Maarek M, Jullien JL, Corone P (1985): Maladied’Ebsteinassociee a une tetralogie de Fallot. Arch Maloeur 78:752-756. Donegan CC, Moore MM, Wiley TM, Hernandez FA, Green JR, Schiebler G1 (1968): Familial Ebstein’s anomaly of the tricuspid valve. Am Heart J 75375-379. Emanuel R, O’Brien K, Ng R (1976):Ebstein’s anomaly: genetic study of 26 families. Br Heart J 385-7. Fyfe DA, Kline CH (1990): Fetal echocardiographic diagnosis of congenital heart disease. Ped Clin N Am 37:45-67. Gueron M, Hirsch M, Stern J , Cohen W, Levy M (1966): Familial Ebstein’s anomaly with emphasis on the surgical treatment. Am J Cardiol 18:105-111. Harper PS (1988): “Practical Genetic Counselling,” 3rd ed. Wright, Butterworth, p. 219.

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Kleinman CS, Donnerstein RL, Devore GR et a1 (1982): Fetal echocardiography for evaluation ofin utero congestive heart failure. N Engl J Med 306:568-575. Lange LW, Sahn DJ, Allen HD, Goldberg SJ, Anderson C, Giles H (1980): Qualitative real-time cross-sectional echocardiographicimaging of the human fetus during the second half of the pregnancy. Circulation 62:799-806. Lo KS, Loventhal JP, Walton JA (1979): Familial Ebstein’s anomaly. Cardiology 64:246-255. Pierard LA, Henrard L, Demoulin J C (1985): Persistent atrial standstill in familial Ebstein’s anomaly. Br Heart J 53594-597. Roberson DA, Silverman NH (1989): Ebstein’s anomaly: echocardiographic and clinical features in the fetus and neonate. JACC 51300-1307. Rosenmann A, Arad I, Simcha A, Schaap T (1976):Familial Ebstein’s anomaly. J Med Genet 13:533-535. Siebert JR, Barr M, Jackson JC, Benjamin DR (1989): Ebstein’s anomaly and extracardiac defects. Am J Dis Child 143570-572. Silverman NH, Kleinman CS, Rudolph AM et a1 (1985): Fetal atrioventricular valve insufficiency associated with non-immune hydrops: A two-dimensional echocardiographic and pulsed Doppler ultrasound study. Circulation 72:825-832. Simcha A, Bonham-Carter RE (1971): Ebstein’s anomaly: clinical study of 32 patients in childhood. Br Heart J 33:46-49. Veille JC, Mahowald MB, Sivakoff M (1989):Ethical dilemmas in fetal echocardiography. Obstet Gynecol 73:710-714. Watson H (1974): Natural history of Ebstein’s anomaly of the tricuspid valve in childhood and adolescence. Br Heart J 36:417-427. Zalzstein E, Koren G, Einarson T, Freedom RM (1990): A case control study on the association between first trimester exposure to lithium and Ebstein’s anomaly. Am J Cardiol 65:817-818.

Ebstein anomaly: report of a familial occurrence and prenatal diagnosis.

The Ebstein anomaly is a rare congenital heart disease involving the position and structure of the tricuspid valve. Although most cases are sporadic, ...
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