Beckwith-Wiedemann Syndrome and Isolated hemihypertrophy

Also called: Beckwith-Syndrome, BWS, Macroglossia-Omphalocele-Visceromegaly Syndrome

What is Beckwith-Wiedemann syndrome and isolated hemihypertrophy?

Beckwith-Wiedemann syndrome is a genetic disorder that can cause overgrowth of body parts (hypertrophy) along with other medical findings (described below). The overgrowth may be limited to one body area, such as the legs, head or tongue, or it may involve several different areas of the body. When overgrowth is limited to only one side of the body, it is called hemihypertrophy or hemihyperplasia. When a person has hemihypertrophy with no other signs of Beckwith-Wiedemann syndrome that person may be considered to have isolated hemihypertrophy.

People with Beckwith-Wiedemann syndrome or isolated hemihypertrophy also have an increased risk of developing certain cancers during childhood. These are usually cancers of the kidney or liver. Less commonly, cancers can arise from muscle or other tissues, or from the adrenal glands.

Most children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy grow up to be healthy adults. By the time the children are teenagers, their growth tends to become more typical and their cancer risk falls to that of the general population. Adults with these syndromes usually have normal intelligence and lifespan.

What is the cancer risk for people with Beckwith-Wiedemann syndrome or isolated hemihypertrophy?

Children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy are at increased risk of developing a kidney tumor called Wilms tumor. Most Wilms tumors develop before the age of 5 years, but some children can develop Wilms tumor later. Children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy also have an increased risk of developing a liver cancer called hepatoblastoma. Most hepatoblastomas develop by 2 years of age.

Rarely, children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy develop other types of cancer, including the following:

  • Tumor in tissues with similar origins of nerve cells (neuroblastoma)
  • Tumor in the adrenal glands (pheochromocytoma, adrenocortical carcinoma)
  • Tumor in the muscle tissues (rhabdomyosarcoma)

The estimated risk for all types of tumors in children with Beckwith-Wiedemann syndrome is between 4% (about 1 in 20) and 21% (about 1 in 5). The estimated risk for all types of tumors in children with isolated hemihypertrophy is about 6% (about 1 in 17). The greatest time of risk is in the first 8 years of life.

What are other physical findings seen in people with Beckwith-Wiedemann syndrome?

Children with Beckwith-Wiedemann syndrome may have the some of the following additional physical findings.

  • Creases or pits in or around the ear lobe
  • Omphalocele, a birth defect in which organs that are normally in the abdomen poke out through the belly button (navel). These organs are covered in a sac made of a thin layer of body tissue. This condition is corrected surgically during infancy.
  • Umbilical hernia, a birth defect in which there is a bulge near and under the belly button (navel). Correcting this through surgery may or may not be required, depending on the size of the hernia.
  • Larger than normal organs in the abdomen (visceromegaly)
  • Abnormal kidney(s)
  • Abnormal heart
  • A gap in the roof of the mouth (cleft palate), which is corrected surgically
  • Blood sugar levels that are too low as a newborn (hypoglycemia)

Other, minor physical issues may include: excessive amniotic fluid during pregnancy (polyhydramnios); separation of the right and left sides of the main abdominal muscle (diastatsis recti); noncancerous blood vessel growths (hemangiomas); or port-wine stain birthmarks (nevus flammeus).

What causes Beckwith-Wiedemann syndrome or isolated hemihypertrophy?

Most cases of Beckwith-Wiedemann syndrome and some cases of apparently isolated hemihypertrophy are caused by changes known as “methylation defects” on a region of chromosome 11 called 11p15. Chromosomes are the thread-like structures that carry genetic information telling cells within the body how to function. The genes located at 11p15 help control how and when cells grow, divide and die. The methylation defects seen in Beckwith Wiedemann syndrome or isolated hemihypertrophy interfere with how these genes work. As a result, cells with 11p15 methylation defects can grow and divide in an abnormal manner. Researchers believe this contributes to the enlarged body parts and possibly also to tumor formation.

Most children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy (about 80%–85%) do not inherit the condition from a parent. These children have no history of the syndrome in their family. In these cases, the methylation defects on chromosome 11p15 either happened in the egg or sperm cell that formed the child or in one of the child’s cells during pregnancy. These children are the first in their families to have Beckwith-Wiedemann syndrome.

A smaller proportion of children with Beckwith-Wiedemann syndrome have the condition because of changes within a specific gene known as CDKN1C or because of an abnormal genetic makeup of chromosome 11p15 (this is called “uniparental disomy”).

The risk of passing the condition to future children differs depending on what type of change is found on chromosome 11p15 after genetic testing. A genetic counselor can help to explain the risks.

How are people with Beckwith-Wiedemann syndrome or isolated hemihypertrophy screened for tumors?

Children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy are at increased risk of developing Wilms tumor and hepatoblastoma, and have a small increased risk to develop other types of cancers. Most of these cancers can be cured with proper treatment if they are found early. Screening is recommended for all children with this condition. The goal of screening is finding and treating tumors early to allow the best outcome for patients. People with Beckwith-Wiedemann syndrome or isolated hemihypertrophy should be managed by a doctor who knows these conditions well.

Recommended screenings for children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy include the following:

  • Yearly physical exams by a doctor who knows these syndromes well.
  • Ultrasound exams of the kidneys +/- abdomen. These ultrasounds should be started in infancy and repeated every three months until the age of 10 years. Until the age of 4 years, the ultrasound exam should include views of the liver, kidneys and other internal organs (abdominal ultrasound). After age 4, the risk of cancer in the liver or other internal organs drops dramatically, so the exam should focus only on the kidneys (renal ultrasound).
  • A blood test to check the levels of alpha-fetoprotein (AFP). AFP is a protein that is often released by liver cancer cells. Checking a child’s levels of AFP in the blood can help screen for liver cancer. Levels should be checked beginning in infancy and repeated every 6–12 weeks until the age of 4 years.

It is possible that the recommended screenings may change over time as doctors learn more about Beckwith-Wiedemann syndrome or isolated hemihypertrophy. Parents should discuss all screening options for their child with a doctor who knows these syndromes well. Because Beckwith-Wiedemann syndrome and isolated hemihypertrophy are complex conditions, it is important that parents seek out an experienced doctor for their child.

How is genetic testing for Beckwith-Wiedemann syndrome and isolated hemihypertrophy done?

The doctor may suspect Beckwith-Wiedemann syndrome or isolated hemihypertrophy after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about a person’s health and the health of other family members.

The genetic counselor or doctor will record which family members have developed signs and symptoms of Beckwith-Wiedemann syndrome or isolated hemihypertrophy and at what ages these occurred. From this information they will create a family tree. If Beckwith-Wiedemann syndrome or isolated hemihypertrophy is suspected in a child or other family members, the doctor or genetic counselor will likely recommend genetic testing.

Diagnostic genetic testing

If the doctor or genetic counselor suspects that a person has Beckwith-Wiedemann syndromeor isolated hemihypertrophy, diagnostic testing may take place as follows:

  • A blood sample is collected.
  • DNA is isolated from the cells in the sample. A person’s genes are made of DNA.
  • Specific areas on chromosome 11p15 are checked for possible changes. If there are differences, a genetic specialist decides if they might be associated with Beckwith-Wiedemann syndrome or isolated hemihypertrophy.
  • If genetic changes are found that reveal Beckwith Wiedemann syndrome or isolated hemihypertrophy, a genetic counselor will work with the family in the following ways:
    • To help the family understand the cancer and other health risks of Beckwith-Wiedemann syndrome or isolated hemihypertrophy
    • To review what cancer screening tests are available
    • To find out if other family members should consider genetic testing
    • To help with decisions about prenatal genetic testing

It is important to remember that genetic testing does not always find genetic changes on chromosome 11p15 for all people with Beckwith-Wiedemann syndrome or isolated hemihypertrophy. This is because researchers do not yet fully understand all of the genetic causes of this condition. If no changes are found, this does not exclude a diagnosis of Beckwith-Wiedemann syndrome or isolated hemihypertrophy. For that reason, we recommend that all children who have a clinical diagnosis of Beckwith-Wiedemann syndrome or isolated hemihypertrophy receive the same medical management, regardless of genetic test results.

Prenatal genetic testing

Before considering prenatal genetic testing, parents should talk with a genetic counselor to decide if there is risk of passing on Beckwith-Wiedemann syndrome or isolated hemihypertrophy to their children. Only certain genetic types of Beckwith-Wiedemann syndrome or isolated hemihypertrophy are inherited. Most are not passed on to future children.

If testing would be helpful, prenatal genetic testing may take place either before pregnancy occurs or during pregnancy. People considering prenatal testing should work with a genetic counselor to review the pros and cons of the testing. The genetic counselor can also help parents consider how they wish to handle the results of the testing.

Testing that occurs before pregnancy — Testing that happens before pregnancy is called preimplantation genetic diagnosis (PGD). This type of genetic testing is done along with in vitro fertilization (IVF). PGD offers a way to test embryos for the known cause of Beckwith-Wiedemann syndrome or isolated hemihypertrophy before placing them into the uterus.

Testing that occurs during pregnancy — Testing can be used to see if a pregnancy is affected with the known cause of Beckwith-Wiedemann syndrome or isolated hemihypertrophy. A doctor gathers cells from the pregnancy in one of two ways:

  • Chorionic villus sampling (CVS) — during the first trimester (first three months)
  • Amniocentesis — during the second trimester or later (last six months)

Collected tissue can be checked for the presence of the cause of Beckwith-Wiedemann syndrome or isolated hemihypertrophy identified in the family.

Both of these tests carry minor risks and should be discussed with an experienced doctor or genetic counselor.

Special concerns

Genetic testing for Beckwith-Wiedemann syndrome or isolated hemihypertrophy is a complex process. Those thinking about testing should take time to consider the benefits and risks. They should discuss the process with a genetic counselor before testing is done. If they choose testing, they should review the test results with the doctor or genetic counselor to be sure they understand the meaning of the results.

Sometimes children or adults with Beckwith-Wiedemann syndrome or isolated hemihypertrophy can feel sad, anxious, or angry. Parents who pass on changes that cause Beckwith-Wiedemann syndrome or isolated hemihypertrophy to one or more of their children can feel guilty. Some people with changes that cause Beckwith-Wiedemann syndrome could have trouble getting disability coverage, life insurance or long-term care insurance in some states. Read more about genetic discrimination.

Are there other special health care needs for children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy?

Children with Beckwith-Wiedemann syndrome or isolated hemihypertrophy have a higher risk of cancer. They should monitor their health and adopt healthful habits. It is important to continue to have regular physical checkups and screenings. That way, any cancer can be found early at the most treatable stage.

Other ideas to reduce the risk of cancer include the following:

  • Eat a healthful diet with lots of fruits and vegetables
  • Get regular exercise
  • Avoid smoking or using tobacco products
  • Avoid secondhand smoke

People with Beckwith-Wiedemann syndrome or isolated hemihypertrophy should watch closely for general signs or symptoms that could signal cancer:

  • Pain or enlargement of the abdomen
  • Blood in the urine
  • Aches, pains, lumps, or swelling that cannot be explained

It is important to seek medical help if anything unusual appears.

The St. Jude Web site is designed for educational purposes only and is not engaged in rendering medical advice or professional services. The information provided through this site should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.