- Human pathology

Home > D. General pathology > Genetic and developmental anomalies > assymetry


Thursday 23 November 2006

Humans and all other vertebrates present internal asymmetry along the left–right (L–R) axis. Two types of L–R asymmetry contribute to the final asymmetric arrangement of organs.

The first type is asymmetry of unpaired organs such as the heart, liver, spleen, stomach, small bowl and colon. The embryonic primordia of these organs are formed as midline structures and follow complex patterns of movements resulting in a consistent positioning of these organs along the L–R axis. In some parts, formation of asymmetry is linked to the unilateral regression of initially bilaterally paired primordia, such as occurs during the formation of the vascular system.

The second type of L–R asymmetry is the generation of asymmetry of paired organs, specifically the lungs, the bronchi and the cardiac atrial appendages. These organs acquire distinct right and left forms with right and left referring to their morphology rather than their position. For instance, a lung with three lobes is a right lung while a lung with two lobes is a left lung regardless of their position along the L–R axis. Thus the final arrangement of organs displays a consistent L–R asymmetry of paired and unpaired organs.

Asymmetry of paired and unpaired organs is handed or directional. This means that the global asymmetric L–R organization is consistently orientated with reference to the anteroposterior and the dorsoventral axis in all members of a species. The handed asymmetry is known as situs and the normal disposition of organs is called situs solitus.


The failure to generate normal L–R asymmetry and/or to orientate the handedness or situs results in a spectrum of laterality disturbances or heterotaxia (heterotaxy).

Heterotaxia, translated from its Greek origins to mean ‘other arrangement’ is a common term that is used for all laterality disturbances within this spectrum.

Three types of anatomical derangements can be recognized, each corresponding to defects in either situs orientation, asymmetry of unpaired organs or asymmetry of paired organs:

- 1. Situs inversus totalis is a defect in global situs orientation. It results in a complete mirror image of situs solitus. In this condition, occurring in one out of 6000–8000 newborns, all organs maintain their normal relative position with respect to each other.

- 2. Situs ambiguus is the failure of asymmetry of unpaired organs and thus a condition where at least one organ shows a reversed orientation along the L–R axis. This condition has an estimated incidence at birth of 1/10,000. Situs ambiguus is frequently associated with isomerism.

- 3. Isomerism is a defect in asymmetry of paired organs that usually have distinct right and left forms, but in this condition, are mirror images. Often the cardiac atrial appendages, the bronchi and the lungs are all involved. Ths absence of visceral asymmetry is sometimes referred to as bilateral left-sidedness and bilateral right-sidedness.

  • In left isomerism, the heart has two long narrow atrial appendages and both lungs are bilobed with long hyparterial bronchi. Left isomerism is often associated with polysplenia and right isomerism with asplenia.
  • In right isomerism, both atrial appendages are pyramidal in shape and the lungs are trilobed with short eparterial bronchi.

NB: Ivemark recognized the absence of L–R asymmetry as a pathological criterium and asplenia with isomerism was called Ivemark syndrome. Later asplenia/polysplenia syndrome appeared as a descriptive term. However it has been shown that isomerism of the atrial appendages is a much more constant feature than splenic anomalies. Ivemark and asplenia/polysplenia syndrome do not constitute distinct etiological entities and these terms should be avoided.

See also

- heterotaxy (situs anomalies, laterality disorders)


- Peeters H, Devriendt K. Human laterality disorders. Eur J Med Genet. 2006 Sep-Oct;49(5):349-62. Epub 2006 Jan 3. PMID: 16461029