Heterotaxy syndrome

Heterotaxy syndrome or situs ambiguous (also spelled situs ambiguus, which is etymologically more correct) is a disturbance in the usual left and right distribution of the thoracic and abdominal organs which does not entirely correspond to the complete or partial mirror image. It occurs from an early embryological developmental disturbance with most cases being sporadic. It is also classified under the group of cardiosplenic syndromes.

Epidemiology

The true incidence is not known, but some sources have estimated it to be around 1 per 8,000-25,000 live births.  Approximately 20-25% are associated with the immotile cilia syndrome.

Clinical presentation

This is dependent on severity of the isomerism and presence of associated abnormalities. Where there is congenital heart disease, presentation may be secondary to heart failure or cyanosis. Additionally, malrotation may be a presenting feature.

Pathology

Bronchial anatomy as a key

Bronchial anatomy accurately reflects 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
• eparterial bronchus (along side the artery) - supplies the tri-lobed right lung

In situs ambiguous, there is duplication of either the hyparterial or eparterial bronchus. The associated atria are also duplicated and there are specific changes below the diaphragm (although not left-sided or right-sided duplication) ^1.

Associations

• congenital cardiac anomalies ^1,5 (can be very complex, e.g. single ventricle)
• intestinal malrotation ³
• immune deficiency (when there is asplenia)
• polysplenia
• absence of gallbladder
• total anomalous pulmonary venous drainage (TAPVR)
• immotile cilia syndrome (including Kartagener syndrome)

Radiographic features

Imaging features can be extremely complex.  

There is duplication of the left or right-sided intra-thoracic contents with associated changes below the diaphragm. Classically, there is malposition of the liver, stomach and spleen (which may be absent). Additionally, the vascular supply below the diaphragm may be altered significantly (including SVC duplication) ^1.

Left sided isomerism

• two hyparterial bronchi
• bronchi are short and horizontal
• widened carina
• two bilobed lungs
• two left atria
• midline liver
• multiple spleens/polysplenia (usually along the greater curvature of stomach)
• variable stomach position
• interrupted IVC with aygous or hemiazygous continuation
• associated with less complex CHDcongenital heart disease - usually left to right shunt.⁶

Right sided isomerism (Ivemark syndrome)

• two eparterial bronchi
• bronchi are long and more vertical
• narrow carina
• two tri-lobed lungs
• two right atria
• midline liver
• no spleen (asplenia)
• variable stomach position
• associated with complex cyanotic CHDcongenital heart disease.⁶

Imaging work up

Assessment of the intra-thoracic contents can be made with plain film, echocardiography, CT and MRI as well as angiography. Below the diaphragm, the abdominal contents can be imaged ultrasound, GI contrast studies, CT and MRI.

A minimal work up should include ¹:

• chest radiograph
• echocardiogram: to assess for congenital heart disease
• abdominal ultrasound: to assess intra abdominal contents (especially spleen)
• upper GI series: to rule out malrotation

Treatment and prognosis

Treatment is completely dependant on the malformations (that occur to varying degrees) and the impact that they have clinically.

Specific treatment of congenital heart disease can be seen in their separate articles.

See also

• situs classification
• situs solitus
• situs inversus
• isomerism
• congenital heart disease