Heterotaxy Syndrome in A Preterm Baby-A Rare Case Report with Review of Literature  

Sunilkumar M.N. , Parvathy V.K.
Department of Pediatrics, Amala Institute of Medical Sciences, Amala Nagar, Thrissur-680 555, Kerala, India
Author    Correspondence author
International Journal of Clinical Case Reports, 2015, Vol. 5, No. 41   doi: 10.5376/ijccr.2015.05.0041
Received: 26 Apr., 2015    Accepted: 17 Jun., 2015    Published: 26 Oct., 2015
© 2015 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:

Sunilkumar M.N. and Parvathy V.K., 2015, Heterotaxy Syndrome in A Preterm Baby-A Rare Case Report with  Review of Literature, International Journal of Clinical Case Reports, 5(41) 1-5 (doi: 10.5376/ijccr.2015.05.0041)

Abstract

Heterotaxy syndrome (HTS) is an abnormality where the internal thoraco-abdominal organs are arranged abnormally across the left-right axis of the body. Literature review has reported that it is a very rare condition and has complex cardiac and extracardiac manifestations which requires early surgical intervention. A very rare case report of HTS in a preterm newborn with  an associated  duodenal atresia is presented with a review of literature.

Keywords
Heterotaxy; Heterotaxy syndrome; Complex cardiac abnormalities; Duodenal atresia; Palliative surgery

Introduction
Heterotaxy (HT) is a rare condition in dysmorphology when there is abnormal arrangement of thoracic and abdominal organs across the left-right axis (Jacobs et al., 2007; Sutherland and Ware, 2009). Heterotaxy syndrome (HTS) (from the Greek heteros - different and taxis-arrangement) is the constellation of abnormalities in the position and morphology of the thoraco abdominal viscera. These abnormalities usually do not follow the normal positioning order of organs laterality (situs solitus) or its mirror image (situs inversus) (Bowers et al., 1996; Jacobs et al., 2007; Sutherland and Ware, 2009). HTS is also known as cardiosplenic syndrome or situs ambiguous with right and left isomerism. HTS includes the complex cardiac lesions which are the main cause of severity and mortality in these patients. HTS has an incidence of 1:10 000 births and there is a male predominance at a ratio of 2:1 (Bowers et al., 1996; Lee et al., 2006). The complex cardiac manifestations are seen in 50% to 100% of these children and patients with HTS (Stumpflen et al., 1996). Extra cardiac manifestations of HTS include abnormalities of the urinary system, biliary tract and hepatic abnormalities along with duodenal atresia and gastrointestinal malrotation (Ticho et al., 2000).This case reports a case of HTS in a preterm baby with duodenal atresia.

Case Report

A 7 day old male baby was seen at the outpatient clinic. The birth history revealed that he was born to a 22 year old primi mother at 33 weeks gestation via spontaneous vaginal delivery weighing 1.18 kg elsewhere. The cause of premature delivery was attributed to maternal illness- pregnancy induced hypertension. His parents were of non-consanguineously married. The antenatal ultrasonogram done revealed that he had possibility of a complex congenital heart disease and his parents were informed about it. The parents belonged to middle class socio economic family. The baby was given care at a local hospital after the premature delivery and on day 1 was referred to a higher centre for further management. He was evaluated at a higher centre and an Echocardiogram done revealed that he had complex congenital heart disease, heterotaxy syndrome with left isomerism, common atrium, common atrioventricular valve with severe atrioventricular valvular regurgitation. Single ventricle, side by side great arteries with unrestricted pulmonary blood flow with interrupted inferior vena cava. Electrocardiogram (ECG)done there reported as right axis deviation with QRS axis 120 degree. As the baby was stable hemodynamically the parents were informed about follow up for the cardiac status. The baby was also diagnosed to have duodenal atresia when he developed abdominal distension and the parents were advised surgery for the same. Apart from duodenal atresia, ultrasonogram of abdomen and pelvis was normal with the liver and spleen and other organs intact. The parents did not want surgery there and brought back the child to the local hospital and from there the baby was referred to our centre.

The first Xray taken erect with chest and abdomen (Figure 1A) at local hospital on day 6 of baby’s life showed cardiomegaly, pulmonary fields not plethoric, liver shadow in the right hypochondrium and grossly distended stomach with a double bubble appeareance. The baby was admitted for palliative treatment. The second radiograph (Figure 1B) done here after admission (after 12 hours after the first Xray) shows the very clear double bubble appearance. On general physical examination, baby had  stable vitals. He was afebrile, heart rate 122/minute, respiratory rate 52/minute, His oxygen saturation was 94% at room air. All peripheral pulses were equally felt. Blood pressure was 74/36 mm Hg in right upper limb, 73/35 mm Hg in left upper limb. 72/76 mm Hg in right lower limb. 76/24 mm Hg in left lower limb. Anterior fontanelle was normal. There was no central cyanosis and any significant dysmorphism.His respiratory effort remained good and was active and at times crying vigourously. Abdominal examination revealed gross distension of the abdomen and there was no hepatosplenomegaly. Cardiovascular system examination revealed S1 normal, S2 split,an ejection systolic murmur in the left parasternal border was normal. Respiratory system examination was normal except for occasionally being tachypneic. Genito urinary system examination was normal. He did not have any neurological deficits. The baby was kept nil orally and hydration with intravenous fluids and supportive care such as maintenance of normal temperature, catherisation of urinary bladder to measure the urinary output, intravenous antibiotics as per the NICU protocol with Cefotaxim and Gentamicin was started. The newborn was assessed by the paediatric surgeon and on day 8 of his life the Khimora procedure –duodenostomy was done under local anaesthesia after properly informing the parents and consent. During the surgery the preportal vein was found obstructing the distal lumen and there was grossly dilated stomach and the first part of duodenum. The baby tolerated the procedure and was in the NICU for the further care.

The laboratory investigations were done: On admission-A quick glucose check was 175 mg/dl. Hemogram revealed Hb (12.1 g/dl), PCV (33.7%), total count (11 690/µl), neutrophils (57.6%), lymphocytes (24.5%), eosinophils (0.3%), monocytes (2.5%), basophils (0.1%), ESR (31 mm/hr), and platelets count (75 000/µl). Serum Na+ 137 meq/l, K+ 5.1meq/l, Cl- 87 meq/l, bicarbonate 21 meq/l, glucose 144 mg/dl, total Ca++ 8.8 mg/dl. C Reactive protein was 19.4 mg/dl (normal = <0.6md/dl) BT: 2 minutes CT:12 minutes HIV/HBsAg: Negative, Serum Creatinine: 1.1 mg%, Serum Ca++: 9.0 mg%. Total Serum Bilirubin: 7.7 mg/dl, Indirect serum Bilirubin: 6.3 mg/dl. Urine routine was normal. On day 4 after admission Serum Na+ 137 meq/l, K+ 5.1 meq/l, Cl-106 meq/l, bicarbonate 16 meq/l, glucose 144 mg/dl, total Ca++ 9.8 mg/dl. C Reactive protein was 4.7 mg/dl (normal == <0.6 md/dl) Serum Creatinine: 0.6 mg%, Serum Ca++: 9.0 mg%. Platelet count 100 000 /µl. On day 10 of his life he had respiratory distress and he became lethargic .His blood sugars were normal. He was transfused packed red blood cell concentrate and antibiotics changed to Meropenam injection and was hydrated properly. Then his general condition improved. The third radiograph (Figure 1C) done here after 6 hours after the second Xray shows the decompressed stomach with cardiomegaly and normal lungs. But on day 15 of his life he developed again respiratory distress and on day 16 of his life (11th day after admission) he suddenly developed desaturation and expired in spite of all resucitatory measures given. The cause of the sudden deterioration in the baby’s condition was presumed to multiple factors such as prematurity, sepsis, complex congenital heart disease and heterotaxy syndrome.

 
Figure 1A Photo of the first Xray taken erect with chest and abdomen showed cardiomegaly,pulmonary fields not plethoric, liver shadow in the right hypochondrium and grossly distended stomach with a double bubble appearance
Figure 1B Photo of the second radiograph shows the very clear double bubble appearance
Figure 1C Photo of the the third radiograph shows the decompressed stomach with cardiomegaly and normal lungs


Discussion
In the daily paediatric clinic there are many newborns and children seen with a congenital heart disease (CHD). CHD has a prevalence of 8 per 1 000 live births and the mortality increases with the complexity of the underlying structural cardiac anomaly (Stumpflen et al., 1996). Also many of these cardiac diseases are also associated with structural anomalies related to the respiratory, gastrointestinal, renal and other systems. Heterotaxy is a rare condition in dysmorphology when there is abnormal arrangement of thoracic and abdominal organs across the left-right axis (Jacobs et al., 2007; Sutherland and Ware, 2009; Bowers et al., 1996). The word heterotaxy has origin from the Greek literature: heteros-implies other than, and taxis- denotes arrangement. Heterotaxy syndrome (HTS) is the constellation of abnormalities in the position and morphology of the thoraco abdominal viscera that usually do not follow the normal positioning order of organs laterality (situs solitus) or its mirror image (situs inversus) (Jacobs et al., 2007; Sutherland and Ware, 2009; Bowers et al., 1996). The case presented is a HTS in a preterm newborn and is very rare as was seen in the literature (Bowers et al., 1996; Lee et al., 2006; Jacobs et al., 2007; Sutherland and Ware, 2009).

HTS results as a result of early embryological developmental disturbance and genetic abnormalities. Sporadic cases are seen. HTS has an incidence of 1:10 000 births and there is a male predominance at a ratio of 2:1 (Bowers et al., 1996; Lee et al., 2006; Sutherland and Ware, 2009). The case presented was a male baby. HTS can exists in two forms, ie the right isomerism (RI) and left isomerism (LI) (Bowers et al., 1996; Lee et al., 2006; Jacobs et al., 2007; Sutherland and Ware, 2009). Cyanotic CHD is an important presentation in right isomerism and so they are recognised early in infancy. HTS with left isomerism  presents later in childhood or even in adulthood as it is less associated with complex CHD. Literature review has shown that Asian population has an increased  prevalence of HTS than in the West (Kim et al., 2008). Chromosomal anomalies and single etiological factor for the causation of HTS are under study in various population (Bowers et al., 1996; Lee et al., 2006). 20-25% of HTS are are associated with the immotile cilia syndrome (including Kartagener syndrome). There are reports of families having several members with HTS and the etiology remains unclear (Cesko et al., 1998). The case reported did not have any significant dysmorphism and had complex CHD of the LI.

The clinical presentation is dependent on severity of the isomerism and presence of associated abnormalities (Ticho et al., 2000; Jacobs et al., 2007; Sutherland and Ware, 2009). HT has been well known to alter the development of the heart, liver, lungs, intestines, and spleen. LI is a situation in which paired structures on opposite sides of the left-right axis of the human body are symmetrical mirror images of each other, and tend to have the morphology of the normal left-sided viscerae (Jacobs et al., 2007; Sutherland and Ware, 2009). LI is also known as polysplenia syndrome. There are occurrence of multiple splenules without a spleen. Anomalies such as azygos or hemiazygos continuation of the inferior vena cava are seen. The bronchial anatomy can reflect the atrial situs. The bronchial anatomy on the left and right can be recognised on a well penetrated radiograph and consists of two main bronchi that are anatomically different: hyparterial bronchus (below artery): supplies the bi-lobed left lung and eparterial bronchus (along side the artery): supplies the tri-lobed right lung (Jacobs et al., 2007; Kim SJ et al 2008; Sutherland and Ware, 2009) . In the LI theres is also associated bilateral hyparterial long bronchi, bilateral bilobed lungs and bilateral pulmonary/left atrial appendages. Isomeric left appendages in some patients have pulmonary veins connecting to both the atriae as if both atriums were morphologically left atriums. Other associations are midline/transverse liver along with an intestinal malrotation. The case presented had features with LI with duodenal atresia. RI is a situation when there is occurrence of some paired structures on opposite sides of the left-right axis of the body that are symmetrical mirror images of each other, and have a morphology of the normal right-sided structures. RI is also known as asplenia syndrome.It is characterised by severe cyanotic congenital heat diseases with the absence of spleen. They frequently have bilateral eparterial bronchi, bilateral trilobed lungs, each with a short bronchus. Patients with a RI have without any exception central cyanosis obstruction of the pulmonary outflow tract and pulmonary atresia. Serious extracardiac anomalies have also been associated with RI. Extracardiac abnormalities of HTS are abnormalities of the renal tract, especially biliary atresia, duodenal atresia or compression. The clinical scenario of a late intestinal obstruction in a child with HTS may be a result of gastrointestinal malrotation or gastric volvulus (Ticho et al., 2000; Kim et al., 2008). The LI in the baby presented was hemodynamically stable and the duodenal atresia required surgery.

The ever changing advancement in the field of ultrasonography has helped clinicians and radiologists interested in fetal ultrasonography to detect the congenital anomalies and there lies the significance of HTS as it is associated with many prenatal and perinatal morbidity and mortality in the fetus and the newborn. So it helps in the diagnosis of these problems very early and appropriate measures can be taken depending upon the viability of the fetus ,to continue the pregnancy and also in the undue care of the newborn. The case in the study was detected to have a HTS in the antenatal scan at fifth month of gestation and was under regular follow up. The radiological evaluation especially ultrasonogram in the hands of an experienced radiologist can clinch the diagnosis. Imaging features can be extremely complex (Yoo and Jaeggi, 2008). There could be duplication of the left or right-sided intra-thoracic contents with associated changes below the diaphragm. Malposition of the liver, stomach and spleen (which may be absent) along with an altered the vascular supply above and below the diaphragm may be identified (Kim et al., 2008; Yoo and Jaeggi, 2008).

A case of fetal HTS have been highlighted in literature (Chon et al., 2011). Lee et al. reported six cases of HTS with left isomerism having intra-abdominal anomalies such as including malrotation, biliary atresia and acute appendicitis with polysplenia in only one of them (Lee et al., 2006). HTS in adults have been reported but is rare in paediatric population (Carneiro et al., 2013).

The ECG and abnormalities of cardiac rhythm are important as these children can have varying degrees of heart blocks and can be identified in the ECG. Atrio ventricular block is rare in the RI and is common in LI (Escobar-Diaz et al., 2014). The use of 2D Echo is very worthwhile to diagnose these complex CHD  and is quite challenging for the cardiologist. The 2DEcho and ECG was done again at higher centre and confirmed the HTS with LI and ECG did not show any evidence of a trio ventricular block. An usual protocol in the work up of the case of HTS should include chest radiograph and 2DEcho to assess for congenital heart disease, abdominal ultrasound and barium studies for assessing intra abdominal contents (especially spleen) and find associated intestinal malrotation and anomalies (Kim et al., 2008; Sutherland and Ware, 2009).

The prognosis of patients with HTS is poor. The 1-year mortality postulated is >85% for patients with asplenia and >50% for patients with polysplenia. Isomerism and associated  extra cardiac anomalies also have their consequences. There is risk of septicaemia in the absent spleen situations (Dyke et al., 1991). The preterm newborn had septicemia and excellent antibiotic coverage was administered but succumbed to the illness.

The treatment of these children with HTS is directly proportional to the the nature and severity of the associated cardiac and extra cardiac lesions (Kawashima et al., 1984; Bartz et al., 2006; Serraf et al., 2010). The cardiac surgeries for patients with isomerism in HTS are palliative in nature, as the normal anatomy is rarely achieved. The abnormalities of the systemic venous connection, a partial or total anomalous pulmonary venous connection, a common atrioventricular valve and a single ventricle carry high risk and about 60% of patients with LI have anatomy suitable for biventricular repair. The anomalies in RI are very difficult to correct by this procedure even though cases have been presented (Kawashima et al., 1984; Lin et al., 2000; Bartz et al., 2006). Patients with HTS usually require palliative surgery in the neonatal period. Many procedures have been advocated which include Fontan-type procedure, modified Fontan procedures or the bidirectional cavopulmonary anastomosis (Kawashima operation) (Kawashima et al 1984; Lin et al., 2000; Bartz et al., 2006; Serraf et al., 2010). Patients with HT may have varying degrees of intestinal rotation (Ditchfield and Hutson, 1998). The extra cardiac complications requires early recognition and timely surgery as in the case presented who underwent duodenostomy for the duodenal atresia.

Conclusion
This case study concludes that awareness of HTS among the Paediatricians, Obstreticians and treating Physicians is very important. Once the fetal ultrasonogram in the hands of the experts detects HTS, the pregnancy of the expecting mother should be closely monitored for fetal growth and presence of various associated anomalies. Every newborn with a cardiac disease must be properly examined to look for the presence of an HTS. This will also help in the counselling of the parents about the outcome of the pregnancy and improving maternal and newborn care.

Acknowledgment
The author acknowledges the help of Dr Ajith TA, Professor Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur, Kerala during the preparation of the manuscript.

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