Heterotaxy syndrome or "situs ambiguous" is a rare genetic disorder. It is characterized by several anomalies in the position of the organs and vessels regarding the midline, most of them associated to characteristic morphological alterations of each organ.
The term "situs solitus" should be applied (Fig. 1) when the position of the organs with respect to the midline is normal.
In these cases the heart,
spleen,
stomach and Aorta are located on the left,
and the liver and vena cava on the right.
"Situs inversus" consists in the opposite placing of the organs regarding the normal location (mirror image),
and the "situs ambiguous",
also known as heterotaxy syndrome,
is related to a disordered and unpredictable arrangement of the organs with respect to the situs solitus,
without presenting a mirror arrangement such as situs inversus or a pathognomonic feature. This entity is classically divided into patients with polysplenia and cases with asplenia, or right isomerism and left isomerism,
repectively.
Isomerism refers to a situation in which morphologically right or left structures are found on both sides of the body in the same individual.
In this way,
as we see in Fig. 2,
in patients with right isomerism the two atrial cavities are morphologically right,
both lungs are usually trilobar with short main bronchi,
and may present with asplenia.
This type of isomerism is frequently diagnosed in childhood because of the prentation with cyanotic heart disease or severe respiratory distress,
accompanied by clinical complications derived from the immune alteration due to asplenia,
which could lead to death.
In the left isomerism,
both atriums present a left morphology,
with pulmonary veins,
as well as bilobar lungs with long main bronchial branches.
This subgroup of cases present with polysplenia and interruption of the inferior vena cava (IVC).
Because of the narrow relation of this pathology with mild heart diseases,
it may not be identified until adulthood.
The estimation of the total incidence of the heterotaxy syndrome is difficult to know,
due to the low clinical expression of the variant with polysplenia.
It's probably an underdiagnosed disease.
Approximately,
the incidence of heterotaxy is 1 per 10,000-20,000 live births,
and over 90% of heterotaxy patients present with complex cardiovascular malformation
Recent studies have shown that more than 80 genes are involved in the normal asymmetric left-right organ development.
However,
the exact cause of the heterotaxia syndrome is unknown.
Studies have identified autosomal recessive,
autosomal dominant and X-linked inheritance patterns.
The genes which are implicated in left-right laterality determination and,
therefore,
in the heterotaxy syndrome include ZIC 3,
ACVR2B,
NODAL CRYPTIC,
CRELD-1,
NKX2.5,
SHROOM 3 and LEFTY 2.
Currently,
we know that Xq26.2 (the location of Zinc-finger in cerebellum 3 or ZIC 3 gene) is the position of the genetic cause of X-linked heterotaxy. Roughly 75% of X-linked familial and 1% of sporadic heterotaxy are induced by its mutation.