Ebstein's anomaly associated with trisomy 9p

To the Editor: We describe a female neonate conceived through artificial fertilization, who had a rare association of Ebstein’s anomaly and trisomy 9p. A full-term newborn, a girl, weighing 2594 g, was referred for further examination because of a heart murmur, marked tachypnea, and an unusual appearance. She was born to a 41-yearold, P1G0 mother and a 43-year-old father, who were unrelated. The mother had undergone artificial fertilization at age 40 years because of infertility. There was no family history of congenital heart disease. The initial physical examination demonstrated an unusual appearance with hypertelorism, low-set ears, micrognathia, microcephalus, webbed neck, Simian lines, and hypotonia, which were compatible with trisomy 9p (1–3). Marked tachypnea (78/min) with retraction and a systolic murmur at the fourth left sternal border with gallop rhythm were also noticed. A chest radiogram on admission showed marked cardiomegaly, with a cardiothoracic ratio of 75%, and increased pulmonary blood flow. Two-dimensional echocardiogram revealed an atrial septal defect and Ebstein’s anomaly. Blood gas analysis showed remarkable acidosis (pH 6.974) and hypercapnea (PCO2, 57 mmHg). The patient was immediately intubated and mechanically ventilated. She was also treated for cardiac failure with intravenous administrations of dopamine hydrochloride and furosemide. However, despite these treatments, the patient died of heart failure at age 25 days. G-banding chromosomal analysis demonstrated her karyotype as 46,XX,der(22)t(9;22)(p11;p11.1) (Fig. 1a). Although her father had normal G-banded chromosomes, her mother’s karyotype was diagnosed as 46,XX,t(9;22)(p11;p11.1) by G-banding analysis (Fig. 1b). The mother was phenotypically normal. Therefore, this was a case of abnormalities in meiotic segregation of a maternal balanced translocation. Only a few patients with Ebstein’s anomaly associated with genetic disorders, including Down’s syndrome and Marfan syndrome, have been reported (4, 5). However, no case report of Ebstein’s anomaly associated with trisomy 9p has been published, and, to our knowledge, this is the first case showing this chromosomal anomaly. Lithium has been implicated as a possible etiologic agent of Ebstein’s anomaly, but the mother had no history of treatment with lithium (6). Recently, some families with a hereditary basis for transmission of Ebstein’s anomaly have been reported (5, 7–9). Schunkert et al. (9), studying a family with various cardiac malformations, including Ebstein’s anomaly, speculated that single dominant mutations in homeobox genes could result in diverse phenotypes. Grant (8) also reported an occurrence of tricuspid atresia and Ebstein’s anomaly in siblings. As suggested by these reports, Ebstein’s anomaly may not necessarily be induced by different etiologies from other cardiac malformations involving the atrial and ventricular septum, the mitral, tricuspid, and aortic valves, which are often associated with trisomy 9p syndrome. Bowen et al. (10) reported a patient associated with trisomy 9 mosaicism and bicuspid tricuspid valve tethering to the septum, which was morphologically similar to Ebstein’s anomaly. The report by Bowen et al. suggested a strong relationship between chromosome 9 abnormalities and tricuspid valve malformations. Therefore, it is likely that the mother’s chromosomal abnormality of 46,XX,t(9;22)(p11;p11.1) is not a chance association with the abnormality described. However, this is the first report describing the association between Ebstein’s anomaly and chromosome 9 abnormalities. Masao Nakagawa Hirofumi Kato Hirofumi Aotani Masanori Kondo