Heterotaxy

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] 

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] 

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]

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]

The long-term outlook for people affected by heterotaxy depends on the specific organs that are affected in each individual. When children are diagnosed with heterotaxy soon after birth, it is typically because there are heart defects that require immediate surgery. Although the Fontan procedure may allow affected children to survive infancy, people who have had the procedure typically require a heart transplant later in life.^[4] If people with heterotaxy pass away, it is typically due to heart defects or complications from the Fontan procedure. ^[7]

There is limited data available about the long-term outlook for adults who are diagnosed with heterotaxy. Because most people who are diagnosed in adulthood have less severe symptoms, they may have a better prognosis than children who are diagnosed before birth or during infancy.^[6]