A case of left isomerism with early fetal decompensation

A non-consanguineous couple was referred at 8.5 weeks of gestation for fetal bilateral hydrothorax (Figure 1). The couple had a healthy son of 5 years. In this pregnancy, the mother had bronchitis at 5 weeks of gestation. At 12 weeks the bilateral hydrothorax had resolved and a nuchal translucency of 2.4 mm (95–99th centile) with a fetal heart rate of 130 beats/min (< 5th centile) and a negative a-wave in the ductus venosus was observed. The fetal stomach was right-sided. Chorionic villus biopsy showed a normal male karyotype in the fetus and parental karyotypes were normal. At 15 weeks of gestation, bilateral neck cysts were visible (Figure 2) and the diagnosis of left isomerism with abdominal situs inversus and azygos continuation was made. This was confirmed at 19 weeks of gestation, when the fetal venous return was observed to be abnormal, with azygos continuation and direct drainage of the ductus venosus into the right atrium. Mild cardiac ventricular and arterial (aorta/pulmonary artery ratio, 0.70) disproportion was noted and remained stable throughout the pregnancy. From 30 weeks of gestation, the fetus developed relative bradycardia of 105 beats/min. A male fetus was delivered by Cesarean section (which was a repeat section for cephalopelvic disproportion) at 38 weeks of gestation. Postnatal echocardiography and abdominal ultrasound showed mild ventricular and arterial disproportion, azygos continuation to the right superior vena cava, a low right atrial junctional rhythm of 90 beats/min (Figure 3), three mini-muscular ventricular septal defects (VSDs), a right-sided stomach, a midline liver, and presence of the gallbladder and polysplenia compatible with left atrial isomerism. The neonate was discharged in good health and yearly cardiac evaluation was planned. At the time of writing, the infant was 16 months of age and in good health, with spontaneous closure of the mini-VSDs. Ultrasound image at 8.5 weeks of gestation, showing embryonic thoracic fluid. Ultrasound image at 15 weeks of gestation, showing the presence of a lateral neck cyst. Neonatal electrocardiogram: the P-wave is negative in II and III, diagnostic for low atrial junctional heart rhythm. The outcome of early first trimester bilateral fetal pleural effusion is usually poor. With the majority of cases occurring in conjunction with an underlying chromosomal anomaly (predominantly 45,X0), the reported incidence of early fetal death is > 80%1. In our case, the bilateral pleural effusion had resolved by 12 weeks of gestation, but an increased nuchal translucency and a negative a-wave in the ductus venosus in addition to an underlying left atrial isomerism became apparent. In the second trimester, an abnormal fluid collection in the posterior neck region was visible. Typical findings in left isomerism (bilateral left-sidedness) are bilateral morphological left atrial appendages (left atrial isomerism), viscerocardiac heterotaxy, multiple cardiac anomalies (with a predominance of atrioventricular septal defects and pulmonary stenosis), junctional rhythm due to hypoplasia of the sinoatrial node, congenital heart block, bilateral morphological left (bilobed) lungs, polysplenia, intestinal malrotation, and interruption of the inferior vena cava (IVC) with azygos continuation2, 3. The IVC is interrupted in its intrahepatic part and blood flows via the azygos (former right supracardinal vein) or hemiazygos (former left supracardinal vein) into the superior vena cava, and then in the majority of cases into the atrium. The condition arises embryologically from a failure of the right vitelline vein to anastomose with the right subcardinal vein, together with persistence of the supracardinal veins. The hepatic veins, mainly the right hepatic vein, are connected to the right-sided atrium directly via a persisting sinus venosus. The separate entrance of the right hepatic vein into the right-sided atrium is always present in left atrial isomerism, with an interrupted IVC found in 80% of cases3. Rhythm disturbances are common in left isomerism, since the sinus node is hypoplastic in cases of two left atria. Heart block is more frequently observed in left isomerism with atrioventricular septal defects4. Slow atrial rates associated with junctional escape, as seen in the present case, are common and do not alter the prognosis5. The outcome in left isomerism is dependent on the presence of heart block and hydrops, major cardiac malformations6 and extrahepatic biliary drainage. The mechanism for reversible early fetal decompensation in the present case (early thoracic fluid, increased nuchal translucency, negative a-wave in the ductus venosus) is most likely the result of a temporary right ventricular cardiac failure7, 8 or of a lymphatic disorder, given that the persistence of lateral neck cysts at 15 weeks of gestation were described as a jugular lymphatic distension, where the jugular sacs fail to connect with the jugular veins9. Of particular interest in this case was the excellent neonatal outcome following early fetal decompensation. I. Witters*, P. Debois , J. P. Fryns*, K. Devriendt*, M. Gewillig , * Center for Human Genetics, University Hospital Leuven, Leuven, Belgium, Department of Pediatric Cardiology, University Hospital Leuven, Leuven, Belgium, Department of Obstetrics and Gynecology of A. Z.