Rare Hematology News

Disease Profile

Heterotaxy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

Q89.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Heterotaxia; Heterotaxy syndrome; Visceral heterotaxy;

Categories

Congenital and Genetic Diseases

Summary

Heterotaxy is a condition characterized by internal organs that are not arranged as would be expected in the chest and abdomen. Organs are expected to be in a particular orientation inside of the body, known as situs solitus. Heterotaxy occurs when the organs are not in this typical orientation, but are instead in different positions in the body. This most commonly causes complications with the heart, lungs, liver, spleen, and intestines. Specific symptoms include not getting enough oxygen throughout the body, breathing difficulties, increased risk for infection, and problems digesting food. Heterotaxy may be caused by genetic changes (mutations), exposures to toxins while a woman is pregnant causing the baby to have heterotaxy, or the condition may occur sporadically. The condition is typically diagnosed through imaging such as an echocardiogram or an MRI. Treatment depends on the specific symptoms of each person, but typically includes heart surgery and monitoring by a team of specialists.[1] 

Symptoms

Heterotaxy is characterized by having internal organs that are not arranged as would be expected in the chest and abdomen. This can cause organs such as the heart, lungs, liver, intestines, and spleen to not work correctly. Symptoms of these organs working incorrectly may include breathing difficulties, having a bluish color to the skin (cyanosis), and problems digesting food. For some people with heterotaxy, the only sign may be a heart defect.[2] Others may have twisting of the intestines (malrotation). People with heterotaxy may have a missing spleen (asplenia) or they may have a spleen that is divided into many smaller parts (polysplenia). If the function of the spleen is affected, this can cause a reduced ability to fight infections.[1][3]

Most people with heterotaxy are first found to have the condition shortly after birth when they have symptoms related to a heart defect. However, other individuals are not diagnosed until later in childhood or adulthood due to problems with the intestines or liver that may cause abdominal pain or vomiting.[4] Other adults with heterotaxy are diagnosed because they were receiving imaging for other medical problems. In this case, a diagnosis of heterotaxy is an incidental finding.[5]

Cause

Heterotaxy can have many different possible causes. Changes (mutations) in over 60 genes have been associated with heterotaxy.[4] These cases have been found to show several different pattern of inheritance, including autosomal dominant, autosomal recessive, or X-linked. Other cases of heterotaxy are not inherited from either parent. Instead, the genetic change is occurring for the first time (de novo) in the affected individual.[1]

Some cases of heterotaxy are caused by an exposure to a toxin or chemical that was encountered while an individual’s mother was pregnant. In this case, the chemical may have caused the baby to develop incorrectly, resulting in organs that are not located in the correct place inside the body.[1]

Finally, in some cases it is not known exactly what caused heterotaxy. It could be that these individuals have a mutation in a gene that we do not yet know to be associated with heterotaxy, or it may be that the error in development occurred for other reasons that are not yet understood.[1] 

Diagnosis

Heterotaxy is typically diagnosed by imaging of the internal organs through a CT scan or an MRI. More specific imaging of the heart such as an echocardiogram or an electrocardiogram may also be used to diagnose the condition.[3] If heterotaxy is suspected, further tests may be completed to check for the functioning of the internal organs. For example, blood tests may be done to make sure the spleen is working properly, and an endoscopy may be recommended to determine if the intestines are malrotated. Renal ultrasounds may also determine if the kidneys are in the correct location.[4]

Treatment

The treatment for heterotaxy depends on the specific organs that are affected in each individual. In infants diagnosed with the condition, heart surgery may be necessary to correct any heart defects. For some individuals, this may require multiple procedures to correct the defect. One common procedure is known as a Fontan procedure, which creates a single ventricle of the heart that is responsible for pumping blood both throughout the body and to the lungs. Other surgical procedures such as the Ladd procedure may be necessary to correct an intestinal malrotation.[6]

Other treatment options include inserting a pacemaker to control the rhythm of the heart. Some individuals may require medications to lower blood pressure to reduce stress on the heart. Vaccinations or antibiotics that are taken even when there isn’t an infection (prophylactic antibiotics) may be recommended to make up for a spleen that isn’t functioning properly. In some cases, a heart transplant may be necessary when individuals who had surgical corrections as infants get older. A multidisciplinary team of doctors may be recommended to follow a person who is diagnosed with heterotaxy.[4]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.

          References

          1. Heterotaxy syndrome. Genetics Home Reference; January 2016; https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome.
          2. Bouvagnet P. Heterotaxia. Orphanet. July 2006; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=450. Accessed 11/9/2011.
          3. Cohen MS. Heterotaxy Syndrome (Isomerism). Children’s Hospital of Philadelphia; July 1, 2013; https://www.chop.edu/conditions-diseases/heterotaxy-syndrome-isomerism.
          4. Chin AJ. Heterotaxy Syndrome and Primary Ciliary Dyskinesia. Medscape Reference. May 9, 2014; https://emedicine.medscape.com/article/896757-overview.
          5. Rameshbabu CS, Gupta KK, Qasim M, and Gupta OP. Heterotaxy Polysplenia syndrome In An Adult With Unique Vascular Anomalies: Case Report With Review of Literature. Heterotaxy Polysplenia syndrome In An Adult With Unique Vascular Anomalies: Case Report With Review of Literature. July 2015; 9(7):22-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638408/.
          6. Salavitabar A, Anderson BR, Aspelund G, Starc TJ, and Lai WW. Heterotaxy syndrome and intestinal rotational anomalies: Impact of the Ladd procedure. Journal of Pediatric Surgery. October 2015; 50(10):1695-1700. https://www.ncbi.nlm.nih.gov/pubmed/25783348.
          7. Shiraishi I and Ichikawa H. Human Heterotaxy Syndrome: From Molecular Genetics to Clinical Features, Management, and Prognosis. Circulation Journal. 2012; 76:2066-2075. https://www.jstage.jst.go.jp/article/circj/76/9/76_CJ-12-0957/_pdf.

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