What is heterotaxy syndrome (isomerism)?

Heterotaxy syndrome is a rare birth defect that involves the heart and other organs. The beginning of the word (hetero-) means “different” and the end (–taxy) means “arrangement.”

There are different forms of heterotaxy syndrome. All usually involve heart defects of varying types and severity. In addition, organs such as the stomach, intestines, liver, and lungs may be in abnormal places in the chest and abdomen.

• The intestines may have malrotation, which is when the loops of the bowel are lined up incorrectly. With this problem, the bowel can twist on itself (volvulus). Many children with malrotation need abdominal surgery to correct it.
• Some children with heterotaxy syndrome can have a very serious condition of the liver called biliary atresia. This also may require surgical intervention.
• There may also be irregularities with the skeleton, central nervous system, and urinary tract.
• In some cases of heterotaxy syndrome, the spleen may not work correctly or may be missing entirely. This can cause many problems, because the spleen helps the body fight infections. When the spleen is missing or doesn’t work correctly, patients have a more difficult time recovering from surgeries or infections (patients with heterotaxy may require multiple surgeries). In some cases, there may be a functioning spleen, but it may be divided into several smaller spleens (polysplenia).
• Sometimes children with heterotaxy syndrome have dextrocardia syndrome. This means the heart is in the right chest instead of the left chest.

Here are general descriptions of two types of heterotaxy syndrome. The morphology (structure) of the heart varies from child to child. The Cardiac Center team will explain your child’s heart structure to you in detail. Types of heterotaxy syndrome include:

• Right atrial isomerism: Children with this condition have multiple heart defects. They may have septal defects (holes between the tissue dividing the two sides of the heart) and problems with heart valves, particularly the pulmonary valve. They may also have abnormalities of the blood returning from the lungs to the heart (anomalous pulmonary venous connection). The spleen may be absent (asplenia), and the liver and other organs may be on the wrong side of the body.
• Left atrial isomerism: Children with this condition may have septal defects (holes between the tissue dividing the two sides of the heart) as well as problems with heart valves and the heart’s electrical system. Some children with this problem have complete heart block, which is when the upper-chamber electrical system does not communicate with the lower-chamber electrical system. Most children require pacemakers for this problem. The spleen may be absent, or there may be several small spleens (polysplenia), instead of one spleen.

Signs and symptoms of heterotaxy syndrome

Symptoms of heterotaxy syndrome vary widely and depend on the organs affected.

In nearly all cases of right atrial isomerism and some cases of left atrial isomerism, symptoms will appear at birth or a few days after because the heart defects are severe. In these cases, symptoms include:

• Blue or purple tint to lips, skin and nails (cyanosis)
• Difficulty breathing
• Difficulty feeding
• Lethargy: baby is abnormally sleepy or unresponsive

Sometimes patients with left atrial isomerism don’t have any symptoms and the condition isn’t diagnosed until the child is older or an adult.

Testing and diagnosis of isomerism

In many cases, heterotaxy syndrome is diagnosed before birth. The Fetal Heart Program at The Children’s Hospital of Philadelphia can monitor baby and mother throughout pregnancy and create a plan for labor and care after birth.

CHOP has its own delivery unit on the same floor as cardiac operating rooms and cardiac patient care units. Newborns can be in the care of pediatric cardiologists and specially trained cardiac nurses immediately after birth. The Fetal Heart Program team will discuss delivery in the Garbose Family Special Delivery Unit with mother and family.

After the child is born, diagnosis of heterotaxy syndrome may require some or all of these tests:

• Electrocardiogram (EKG or ECG): a record of the electrical activity of the heart
• Echocardiogram (also called “echo” or ultrasound): sound waves create an image of the heart
• Chest x-ray
• Cardiac MRI: a three-dimensional image shows the heart's abnormalities

Sometimes, cardiac catheterization will be required. In cardiac catheterization, a thin tube is inserted into the heart through a vein and/or artery in either the leg or through the umbilicus (“belly button”).

Other diagnostic tests on other areas of the body will also be required, including renal ultrasound and abdominal ultrasound. Throughout diagnosis and treatment, your Cardiac Center team will work with specialists, such as urologists, gastroenterologists and others, to provide the best care for this complex condition.

Treatment for heterotaxy syndrome

Treatment for heterotaxy syndrome varies depending on the severity of the heart defects and other organ abnormalities.

Most patients with left atrial isomerism will require surgical procedures or catheterization to repair holes in the heart or other problems. Some patients will require implantable pacemakers or defibrillators to control abnormal heart rhythm. In rare cases, patients with left atrial isomerism won’t require any treatment, though they will need to visit a pediatric cardiologist regularly for checkups.

Nearly all patients with right atrial isomerism, and some patients with left atrial isomerism, will require a series of major heart surgeries. Surgeons will reconfigure the heart and circulatory system so that the heart functions with one ventricle (pumping chamber), instead of two. This is called Fontan circulation and requires three open heart surgeries, called staged reconstruction. The procedures include the Norwood procedure, hemi-Fontan or Glenn operation, and the Fontan procedure.

Follow-up care

Between the Norwood and Glenn operations

Though early outcomes for patients with single ventricle heart defects after staged reconstruction have improved dramatically, the period between the Norwood procedure and the Glenn operation remains a very vulnerable time for infants. CHOP created the Infant Single Ventricle Monitoring Program to focus on the care and monitoring of infants with single ventricle heart defects between the first and second reconstructive surgeries.

Through age 18

Patients with Fontan circulation are referred to as single ventricle patients. As these patients get older, doctors are recognizing that, while some do fine, many experience complications, including lung, liver and gastrointestinal diseases. CHOP created the Single Ventricle Survivorship Clinic, part of the Fontan Rehabilitation, Wellness, Activity and Resilience Development (FORWARD) Program, that specializes in the care of these patients, and is researching improved treatments for them.

In addition, as a group, children with complex congenital heart defects who have had open heart surgery as infants are at a higher risk for neurodevelopmental issues when compared to children without congenital heart defects. The Cardiac Center at CHOP created the Cardiac Kids Developmental Follow-up Program to provide evaluation, screening and clinical care for children with complex congenital heart disease who are at risk for neurodevelopmental problems.

All children with heterotaxy syndrome will require lifelong care by a cardiologist. In many cases, children with this condition will have many needs and will require care from different teams at CHOP for many years.

The family is very important in the child’s care. For instance, in patients who do not have a spleen, an infection can quickly become life-threatening. If the child develops a fever (one sign of infection), the family must take the child to a hospital quickly, as IV antibiotics may be required. Your team at the Cardiac Center will make sure you understand the steps you need to take to help keep your child safe.

Into adulthood

We will help older patients with heterotaxy syndrome transition to an adult cardiologist. The Philadelphia Adult Congenital Heart Center, a joint program of the Children's Hospital of Philadelphia and Penn Medicine, meets the unique needs of adults who were born with heart defects.