Yoshinari Kobayashi

Mirror syndrome associated with fetal transient abnormal myelopoiesis in Down syndrome

To the Editor: Mirror syndrome is an unusual pathological condition in which maternal edema in pregnancy is seen in association with severe fetal and placental hydrops. It was first described by Ballantyne in 1892, and fewer than 100 cases have been reported since then. The pathogenesis and pathophysiology of mirror syndrome remain unclear. We encountered a very rare case of mirror syndrome associated with fetal hydrops due to transient abnormal myelopoiesis (TAM) in Down syndrome. A 41-year-old nulliparous woman was referred to our hospital at 24 wks’ gestation with signs of fetal hydrops. Upon initial examination, fetal ultrasonography revealed hydrops with pericardial effusion, massive ascites, and skin edema (Fig. 1a–c). Congenital heart anomalies were also detected: an atrioventricular septal defect, double outlet right ventricle and mild tricuspid regurgitation. The cardiothoracic area ratio was 67% and the lung-thoracic area ratio was 19%. Also seen were a cystic mass at the posterior neck region (Fig. 1a), hepatosplenomegaly, and hyperechoic bowel (Fig. 1b). The middle cerebral artery peak systolic velocity was markedly elevated to 2.0 multiples of median (MoM), suggesting severe anemia. Amniocentesis was performed, and fetal karyotyping revealed trisomy 21 (47, XX, +21). Daily ultrasound examinations showed progressive worsening of the fetal hydrops and hydropic placenta (Fig. 1d) and a progressive decrease in the amniotic fluid volume. The lungthoracic area ratio reduced to 14%, suggestive of pulmonary hypoplasia. At 26 wks’ gestation, the mother complained of mild dyspnea. Physical examination revealed leg edema, and her body weight had increased by 3.6 kg in 1 wk. Her blood examination revealed anemia, low hematocrit, and elevated uric acid. Based on these findings, a diagnosis of mirror syndrome manifesting as maternal pulmonary edema was made, and the patient underwent an urgent Cesarean section at 27 wks’ gestation. The patient delivered a 1712-g girl. The neonate’s 1and 5-min Apgar scores were 1 and 1, respectively. Analysis of the umbilical cord blood revealed severe anemia (hemoglobin 1.5 g/dL) and the appearance of 17% blasts, suggesting TAM. The neonate died 1 h after birth due to hypoxia and metabolic acidosis. A postmortem examination was performed and confirmed cutaneous edema, pericardial effusion, and ascites. Complex cardiac anomalies were confirmed to be as indicated clinically by ultrasonographic analysis. The lung weight/body weight ratio was 0.0075 (<0.015), suggestive of pulmonary hypoplasia. Hepatosplenomegaly (liver weight: 93.8 g; spleen weight: 7.2 g) was confirmed. The liver was anemic and yellowish, and histological examination revealed numerous dysplastic megakaryocytes, including large megakaryocytes with hyperlobulated, hyperchromatic nuclei and small megakaryocytes with irregular-contoured, hypoor