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.