Heterotaxy syndrome - ACVR2B, CFAP53, CFC1, CITED2, CRELD1, DNAH11, DNAH5, DNAI1, FOXH1, GATA4, GDF1, GJA1, LEFTY2, MMP21, NAT10, NKX2-5, NODAL, SESN1, SHROOM3, SMAD2 and ZIC3 genes.


Heterotaxy syndrome is an alteration in which the internal organs are abnormally arranged in the thorax and abdomen. Affected people have complex birth defects that affect the heart, lungs, liver, spleen, intestines and other organs.

In the organism, the organs in the thorax and abdomen have a certain place on the right or left side. This normal arrangement of the organs is known as solitus situs. However, the orientation of internal organs is rarely found in situs inversus. This situation usually does not cause any health problems, unless it occurs as part of a syndrome that affects other parts of the body. In the Heterotaxia Syndrome the distribution of the internal organs is between solitus situs and situs inversus. Unlike situs inversus, the abnormal arrangement of the organs in Heterotaxia Syndrome often causes serious health problems.

This disease alters the structure of the heart, including the fixation of the large blood vessels that carry blood to and from the rest of the body. It can also affect lung structure, such as the number of lobes in each lung and the length of the bronchi. In the abdomen, it can cause asplenia or polysplenia. In addition, the liver may be located in the center of the body instead of in its normal position to the right of the stomach. Some affected individuals also have an incorrect intestinal rotation. Depending on the organs involved, the signs and symptoms of Heterotaxia Syndrome may include cyanosis, respiratory distress, increased risk of infections, and problems with food digestion. The most serious complications are usually caused by a critical congenital heart disease. Biliary atresia can also cause serious health problems in childhood. Frequently, the Heterotaxia Syndrome is fatal in childhood or childhood, even with treatment, although its severity depends on the specific anomalies involved.

Heterotaxy Syndrome is generally due to changes in the ACVR2B, CFAP53, CFC1, CITED2, CRELD1, DNAH11, DNAH5, DNAI1, FOXH1, GATA4, GDF1, GJA1, LEFTY2, MMP21, NAT10, NKX2-5, NODAL, SESN1, SHROOM3, SMAD2 and ZIC3 genes Proteins encoded from most of these genes play a role in determining left-right asymmetry. This process occurs during the early stages of embryonic development. In some cases, Heterotaxia Syndrome is due to mutations in genes whose participation in the determination of left-right asymmetry is unknown. Rarely, some chromosomal changes such as insertions, deletions, duplications, and other rearrangements of genetic material have been related to this alteration. In some affected people no genetic mutations or other associated risk factors have been identified. In these cases, the cause of the disease is unknown.

This disease may occur isolated or may be a characteristic of other genetic syndromes that have additional signs and symptoms. For example, at least 12% of people with Primary Ciliary Dyskinesia have Heterotaxia Syndrome. In addition to abnormally positioned internal organs, Primary Ciliary Dyskinesia is characterized by chronic respiratory tract infections and infertility. The signs and symptoms of this disease are due to cilia anomalies. It is believed that cilia play a critical role in establishing left-right asymmetry before birth. Studies suggest that certain factors that affect women during pregnancy may also contribute to the risk of developing Heterotaxy Syndrome in your child. These include factors such as diabetes mellitus, smoking, exposure to hair dyes, cocaine and certain laboratory chemicals.

Frequently, Heterotaxia Syndrome is sporadic, which means that only one person in a family is affected. However, about 10% of affected people have a close relative who has a congenital heart defect and no other apparent characteristics of Heterotaxy Syndrome. Isolated congenital heart disease and Heterotaxy Syndrome can present a series of signs and symptoms that may result from a particular genetic mutation, a situation known as variable expressivity. It is also possible that different genetic and environmental factors combine to produce isolated congenital heart defects in some family members and Heterotaxy Syndrome in others.

   When Heterotaxy Syndrome occurs in families, the disease may have an autosomal dominant, autosomal recessive or X-linked inheritance pattern, depending on the gene that is involved. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to express the alteration. Autosomal recessive inheritance means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease. When Heterotaxy Syndrome occurs as a characteristic of Primary Ciliary Dyskinesia, it presents an autosomal recessive inheritance pattern. Finally, in the inheritance linked to the X chromosome, the mutated gene that causes the alteration is found on the X chromosome, one of the two sex chromosomes in each cell.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Heterotaxy syndrome, by means of the complete PCR amplification of the exons of the ACVR2B, CFAP53, CFC1, CITED2, CRELD1, DNAH11, DNAH5, DNAI1, FOXH1, GATA4, GDF1, GJA1, LEFTY2, MMP21, NAT10, NKX2-5, NODAL, SESN1, SHROOM3, SMAD2 y ZIC3 genes, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).