Rom J Leg Med [27] 38-42 [2019] DOI: 10.4323/rjlm.2019.38 © 2019 Romanian Society of Legal Medicine FORENSIC PATHOLOGY. CASE PRESENTATION Sudden death of an infant with heterotaxy syndrome: an autopsy report Shojiro Takasu1,*, Sari Matsumoto1, Yuko Kanto1, Saki Kodama1, Kimiharu Iwadate1 _________________________________________________________________________________________ Abstract: Heterotaxy syndrome (HS) is a rare disorder defined as an abnormality of the thoracoabdominal viscera across the left–right axis, causing high morbidity and mortality. In this case report, the patient was an 11-month-old female infant who was diagnosed at birth to have HS with a univentricular heart and pulmonary atresia. She had undergone the second stage of staging surgery for congenital heart disease 5 months before her death and was preparing at home, under nasal oxygen therapy, for the next surgery. The mother placed the infant on her bed in the prone position without a blanket, for sleeping. After 3 hours, the mother found her child in the same position, face down, unconscious, and not breathing; the infant experienced cardiopulmonary arrest when the ambulance arrived. The autopsy showed the HS to be right atrial isomerism, and asphyxia was observed in the findings. The autopsy results indicate the cause of death to be a combination of congenital heart disease and asphyxia caused by sleeping position. Key Words: forensic, infant, heterotaxy syndrome, congenital heart disease, asphyxia. INTRODUCTION antemortem. Therefore, it is rare that patients who die of HS are observed in forensic autopsy cases. Here we report Heterotaxy syndrome (HS) is a disorder involving on a case of sudden death of an infant with HS. an abnormality of the thoracoabdominal viscera across the left–right axis, causing high morbidity and mortality [1]. CASE REPORT With an incidence of approximately 1 in 10,000 total births, HS is a rare condition [2]. HS is divided into right and Case history left atrial isomerisms. Asplenia, bilateral trilobed lungs, The patient in this case report was an 11-month- bilateral right atria, pulmonary venous anomalies, cardiac old female infant who was born via vaginal delivery at 38 malformations, and symmetric liver are often observed weeks’ gestation to a 26-year-old gravida 2, para 2 mother. in right atrial isomerism, whereas polysplenia, bilateral Her weight at birth was 2316 g [standard deviations (SD), bilobed lungs, bilateral left atria, and pulmonary venous −1.5, compared with normal female newborns]. At birth, anomalies are often observed in left atrial isomerism. she was diagnosed to have HS with a univentricular heart Right atrial isomerism is more likely to be associated with and pulmonary atresia. A chromosomal abnormality of severe congenital cardiac disorders, and operative care, 16p12.2 deletion was revealed through genetic testing. such as the Fontan procedure, is required [3,4]. Although Family history revealed that her parents and 2-year-old genetic abnormalities and environmental factors have sibling had no congenital disease. been previously suggested [5-8], the underlying cause of At 3 months after birth, she underwent ductus HS remains unknown. arteriosus clipping surgery and central shunt surgery Patients with HS are mostly diagnosed (anastomosis of the aorta and pulmonary artery), and at 1) Jikei University School of Medicine, Department of Forensic Medicine, Tokyo, Japan * Corresponding author: Jikei University School of Medicine, Department of Forensic Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan, Tel.: +81 3 3433 1111 ext.2282, Fax: +81 3 3433 7306, E-mail: [email protected] 38 Romanian Journal of Legal Medicine Vol. XXVII, No 1(2019) Figure 2. Horizontal cross-section of the ventricle. Vestigial Figure 1. Petechiae on the surface of the heart. left ventricle was observed (arrow). 6 months after birth, she underwent a Glenn procedure traumatic scars were observed. Palpebral conjunctiva and (anastomosis of the superior vena cava and pulmonary bulbar conjunctiva petechiae were not observed. artery). The infant was discharged from the hospital 1 An internal inspection revealed a heart weight of month after the Glenn procedure but was kept under nasal 57 g [mean (SD) for female infants of the same age [9], oxygen inhalation therapy. She was scheduled to undergo 43.0 (4.4) g], with fibrous adhesion to the pericardium and a Fontan procedure (anastomosis of both the vena cava petechiae on the surface (Fig. 1). There was a small amount and the pulmonary artery) a few months later. of fluid dark red blood retained in the pericardial cavity The mother once placed the infant in the prone after excision of the heart. The heart was morphologically position without a blanket, for sleeping. She found her univentricular and accompanied by pulmonary atresia child in the same position, face down, unconscious, and (Figs 2 and 3). Anomalous inferior vena cava drained into not breathing 3 hours later, and therefore, called for an the left atrium. The superior vena cava was anastomosed ambulance. The infant experienced a cardiopulmonary to the left pulmonary artery (Fig. 3), and there was no arrest when the ambulance arrived, and cardiopulmonary occlusion observed in the anastomotic lesion. A single resuscitation (CPR) was immediately performed. After 1 coronary artery was observed to arise from the aortic root hour of CPR at the hospital, the infant was pronounced and separate into three branches. Sclerosis or embolism dead. A computed tomography scan was performed, but it was not detected in the coronary artery, and there were no did not reveal any signs of hemorrhage or bone fractures. histological findings of acute myocardial ischemia. There was also no indication of malfunction in the oxygen The infant had bilateral trilobed lungs, and inhalation device at the time of death. the weights of the left and right lungs were 44 and 41 Because the cause of death was unclear, g, respectively [mean (SD) for female infants of the medicolegal autopsy was performed at The Jikei University same age [9], 72.1 (16.1) and 88.2 (18.9) g, respectively] School of Medicine 27 hours after death. (Fig. 4). Despite the observation of pulmonary congestion, no petechiae were identified on the surface. Observations Autopsy findings also revealed no histological site of infection. The corpse had a height of 65 cm (SD, −2.9, The liver weighed 231 g [mean (SD) for female compared with infants of the same age) and body weight infants of the same age [9], 348.8 (51.6) g]. There were of 4.9 kg (SD, −4.1, compared with infants of the same no signs of biliary atresia. Histologically, no fatty droplet age). The skin showed general pallor. A mild purple–red infiltration was observed. livor mortis was observed on the dorsal surface of the The spleen and stomach were located on the right trunk, and no discoloration was observed under digital side of the abdominal cavity (Fig. 5). The spleen weighed compression. An obsolete longitudinal surgical scar in the 13.4 g [mean (SD) for female infants of the same age [9], median part of the chest was observed. Besides injection 34.6 (8.0) g]. No histological site of abscess was observed. scars on the bilateral inguen and lower limb, no evident The thymus weighed 6.6 g [mean (SD) for female infants of 39 Takasu S. et al. Sudden death of an infant with heterotaxy syndrome: an autopsy report Figure 5. Spleen and stomach located at the right side of the abdominal cavity. Figure 3. Lumen of the pulmonary artery observed by dissecting the rear side of the artery. No outflow tract from the ventricle was observed. The superior vena cava was anastomosed to the left pulmonary artery (arrow). No occlusion was observed at the anastomotic lesion of the superior vena cava and left pulmonary artery (arrowhead). Figure 4. Bilaterally trilobed lungs. Figure 6. External appearance of the thymus. the same age [9], 33.4 (9.8) g], and subcapsular petechiae [10], as observed in the current case. Some studies have were observed on the surface (Fig. 6). described genetic abnormalities and environmental Toxic drugs or ethanol were not detected in the factors related to HS, including maternal diabetes and the gastric contents. Toxicological, ethanol, and biochemical use of cocaine, opiates, and antithyroid drugs associated examinations were not conducted because of insufficient with this syndrome during pregnancy [5-8]. blood and urine samples. The prognostic markers in liveborn patients The heart was heavy, and the thymus was small with HS include cardiac anomalies (total anomalous compared with the expected visceral weights. Although pulmonary venous return, heart block, right ventricular other organs were smaller compared with the expected outflow tract obstruction, and single ventricle), biliary visceral weight for infants of the same age, they seemed atresia, and infectious/immunological causes [11-13]. to be in the range of the expected visceral weight for an Patients with asplenia frequently have severe bacterial infant of the same physics [9]. infections as a result of immunodeficiency [3,12]. In the current case, right atrial isomerism was suspected based DISCUSSION on the presence of bilateral trilobed lungs. Although the thymus was smaller compared with the expected visceral HS is a rare condition that has high morbidity weight, normal spleen and liver were observed at the and mortality [1]. This syndrome occurs sporadically opposite side of the abdominal cavity, and there was no 40 Romanian Journal of Legal Medicine Vol. XXVII, No 1(2019) during birth. Common causes of cyanotic congenital heart disease include tetralogy of Fallot, pulmonary atresia, tricuspid atresia, double-outlet right ventricle with severe pulmonary stenosis, truncus arteriosus, single ventricle, transposition of great arteries, total anomalous pulmonary venous connection, and Taussing–Bing anomaly [16]. In the present case, the patient had a heavier heart compared with healthy subjects, and a combination of single ventricle and pulmonary atresia was observed (Fig.