Updated 2006-01-18 by Juliana Leite, MD
Original text 1999-05-17 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synomym: Ivemark syndrome, heterotaxia, cardiosplenic syndrome.

Definition: This set of syndromes is due to errors of lateralization of the primary field. It results (with simplifications) in either a fetus with a predominant right-sided ness and an isomeric left side (asplenia: a fetus whose left side is a mirror image of its right side) or left-sidedness and an isomeric right side (polysplenia: a fetus whose right side is a mirror image of its left side). These fetuses are usually recognized because of the associated cardiac anomalies.

Incidence: The incidence is very low, estimated at 1 in 10.000 to 20.000 live births.

Etiology: Autosomal-recessive inheritance with male preponderance in the most of the cases, but there are reports of autosomal dominant and X-linked inheritance too. Heterotaxy syndromes could also occur in chromosomal translocation or deletion in sporadic cases.

Diagnosis: The diagnosis is usually made by the recognition of the cardiac anomalies, in particular, the presence of atrioventricular septal defect, mesocardia (the axis of the interventricular septum being almost anteroposterior) with an endocardial cushion defect, an intrahepatic segment of the umbilical vein that is also oriented anteroposteriorly, and an odd-looking stomach. The abnormal lobation of the lungs is difficult to recognize, and the only instance when it can be done is when a sliver of pleural fluid is infiltrated between the lobes. Another typical finding is the interruption of the inferior vena cava with azygos continuation. The typical findings include an inferior vena cava that is posterior in the upper abdomen (instead of curving anteriorly to enter the right atrium) and the abrupt decrease in size of the inferior vena cava near the diaphragm. An enlarged azygos arch joining the superior vena cava can also be recognized. The presence of a persistent left superior vena cava is rarely recognized, not because it is a challenging finding, but because it is not sought. Color and pulsed Doppler of the splenic artery has been suggested as an aid in the prenatal diagnosis of the syndrome. Other findings include agenesis of the corpus callosum with pachygyria and hydrocephalus.

Genetic anomalies: Although it was thought that the syndrome resulted from a possible mutation in the gene encoding connexin 43 (CX43), this was not supported by further studies.

Differential diagnosis: The cardiac anomalies (in particular, endocardial cushion defect) without the syndrome and trisomy 18 may be included in the differential diagnosis.

Figure 1: schematic drawing of the findings in polysplenia

Figure 2: Polysplenia: Dextrocardia with malposition of the stomach on the right side. The apex of the heart is on the same side as the stomach. A complete form of endocardial cushion defect is noted, with a single atrium.

Figure 3: Horseshoe kidney in front of the great vessels

(All figures reprinted with permission from The Fetus [5])

Associated anomalies:

Prognosis: Asplenia tends to be a more severe disease because of the cyanotic heart lesions and the superimposed infections. Although morbidity and mortality in the neonatal period are determined mainly by the cardinal cardiac defects, the visceral anomalies may strongly affect the long-term outcome of these patients.

Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation of the pregnancy is chosen. Confirmation of diagnosis after birth is important for genetic counseling. The treatment of the infant will be dictated by the cardiac defects.

REFERENCES
1: Noack F, Sayk F, Ressel A. et al. Ivemark syndrome with agenesis of the corpus callosum: a case report with a review of the literature. Prenat Diagn. 2002 Nov; 22(11):1011-5.
2: Marton T, Cesko I, Hajdu J et al. Heterotaxy syndrome, analysis of 13 cases and review of the literature. Orv Hetil. 2002 Feb 10; 143(6):299-301.
3: Abuhamad AZ, Robinson JN, Bogdan D, Tannous RJ. Color Doppler of the splenic artery in the prenatal diagnosis of heterotaxic syndromes. Am J Perinatol. 1999; 16(9):469-73.
4: Cesko I, Hajdu J, Marton T, Tarnai L, Zs Toth E. Familial heterotaxy syndrome. Case report and review of the international. Literature. Orv Hetil. 1998 Nov 15; 139(46):2775-8.
5. Berg C, Geipel A, Smrcek J, Krapp M, Germer U, Kohl T, Gembruch U, Baschat AA. Prenatal diagnosis of cardiosplenic syndromes: a 10-year experience. Ultrasound Obst and Gynecol 2003;22(5): 451-59