Situs ambiguus (from Latin 'ambiguous site'), or heterotaxy, is a rare congenital defect in which the major visceral organs are distributed abnormally within the chest and abdomen.
This does not include the congenital defect situs inversus,[1] which results when arrangement of all the organs in the abdomen and chest are mirrored, so the positions are opposite the normal placement.
Situs ambiguus can also be subdivided into left-isomerism and right isomerism based on the defects observed in the spleen, lungs and atria of the heart.
[2] All patients with situs ambiguus lack lateralization and symmetry of organs in the abdominal and thoracic cavities and are clinically considered to have a form of heterotaxy syndrome.
Heterotaxy syndrome with atrial isomerism occurs in 1 out of every 10,000 live births and is associated with approximately 3% of congenital heart disease cases.
[3] Additional estimation of incidence and prevalence of isomerism proves difficult due to failure to diagnose and underestimation of the disease by clinicians.
[2] Abnormal development of the heart results in impaired doubles of conductive nodes, as well as faulty electrical fibers throughout the ventricles.
Abdominal organs, including the liver, stomach, intestinal tract, and spleen may be randomly arranged throughout the left-right axis of the body.
A majority of left atrial isomeric patients have defects throughout the biliary tree, which is responsible for bile production, even when the gall bladder is functional and morphologically normal.
This biliary atresia can lead to acute problems such as nutrient malabsorption, pale stools, dark urine, and abdominal swelling.
[2] Situs ambiguus has been linked to family history of malformations[8][9] and maternal cocaine use,[10] suggesting both genetic and environmental factors play a role.
[11] Several genes in the TGF-beta pathway, which controls left-right patterning of visceral organs across the body axis, have been indicated in sporadic and familial cases of atrial isomerism.
There is also overlap between genes associated with situs ambiguus and primary ciliary dyskinesia, likely due to the important role of cilia in establishing left-right asymmetry.
[12] The planar cell polarity has an important role in positioning these cilia, and thus genes within this pathway are increasingly associated with situs ambiguus.
Mutations in genes that encode proteins in the TGF-beta pathway, including NODAL, NKX2-5, and ZIC3, have been linked to tetralogy of Fallot and hypoplastic left heart syndrome.
Under normal development, the bronchial tree consists of two main bronchi that are anatomically different:[citation needed] In situs ambiguus, there is a duplication of either the hyparterial or eparterial bronchus.
Diagnostic criteria for atrial isomerism includes observation of symmetry of thoracic visceral organs upon echocardiogram, arrhythmia upon electrocardiogram, and chest x-ray for confirmation of the heart's location across the left-right axis.
In addition, a series of gastrointestinal tests can be conducted for observation of intestinal malrotation, as well as a scan of the liver and spleen for biliary function.
It is not possible to return the bowel to a normal morphology[21] However, 89% of patients that undergo the Ladd surgery experience a complete resolution of symptoms.
[citation needed] Right-atrial and left-atrial isomerism and associated pulmonary issues are treated in a series of steps based on the severity of symptoms.
[citation needed] There have been vast amounts of research on the clinical features, racial disparities, and physiological mechanisms of heterotaxy syndrome dating back to 1973.
[citation needed] Mishra et al. published a review in November 2015 describing current knowledge of cardiac and non-cardiac abnormalities associated with situs ambiguus.
[28] Individuals of Asian descent show a higher prevalence of heterotaxy syndrome in general than members of the Western world.