Beckwith-Wiedemann Syndrome (BWS)

Beckwith-Wiedemann syndrome (BWS) is a rare, congenital (present at birth) overgrowth condition that carries a higher risk of several types of cancer in children.

What is Beckwith-Wiedemann syndrome (BWS)?

In children with Beckwith-Wiedemann syndrome (BWS), some parts of the body grow more than they should (called an overgrowth syndrome). This means a child might have a high birth weight or might have one arm or leg that is bigger than the other. BWS also can affect other parts of the body, such as the tongue .

In addition to growth changes, children with BWS have a higher risk of several types of cancer. These cancers are called embryonal cancers. Embryonal cancers come from early cells that normally mature into organs like the liver or kidneys. When these cells do not mature as they should, it can result in cancer. For example, early liver cells can develop into a tumor called hepatoblastoma. Similarly, early kidney cells can develop into a tumor called Wilms tumor.

Signs and symptoms of Beckwith-Wiedemann syndrome (BWS)

Beckwith-Wiedemann syndrome  is a spectrum, meaning no two children with BWS may look exactly alike or have the same symptoms. Some symptoms of BWS may include:

• Enlarged tongue
• Hemihyperplasia, one side of the body is larger than the other side
• Abnormally high birth weight
• Low blood sugar level at birth, which might need treatment to improve or blood tests to monitor
• Abdominal (belly) wall defects, where layers of the belly wall, such as muscles, connective tissue, and/or skin, are not closed or formed at birth.
• Large organs (kidneys, liver, or spleen)
• Some childhood cancers, including Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma  
• Earlobe creases or pits on the back of the ear
• A red or pink birthmark on the face near the forehead, eyelids, or the back of the neck

What causes Beckwith-Wiedemann syndrome (BWS)?

BWS can be caused by either a change in a gene (mutation) or a change in gene expression (rather than a change in the gene itself).

About 1 in 6 cases of BWS are linked to gene changes. The most common is a change in the CDKN1C gene. People with gene changes causing BWS may have a family history of BWS and can pass it on to their children.

But most cases of BWS are caused by changes in the expression of genes. For most gene pairs, the gene inherited from a person’s mother and father are both expressed. In some cases, such as BWS, the gene inherited from one parent is expressed more than the other. This happens by a process called imprinting. Because most cases of BWS are caused by a change in gene expression and not changes to the gene itself, most cases are not inherited or passed from parent to child.

How common is Beckwith-Wiedemann syndrome (BWS)?

Studies suggest BWS affects about 1 in 10,340 children born worldwide. It may be even more common. Some people with BWS have mild signs or symptoms, which means it may go undiagnosed.

How is Beckwith-Wiedemann syndrome (BWS) diagnosed?

BWS may be diagnosed based on clinical symptoms or a combination of clinical symptoms and genetic testing . Genetic testing for BWS may include methylation testing [ (looking at how well the body is functioning ) and/or chromosome testing  (looking for gene changes).

There is no broadly accepted clinical criteria for diagnosing BWS, though a few have been proposed. Symptoms most suggestive of BWS include:

• Enlarged tongue (macroglossia)
• Unusually high birth weight
• Enlargement of one side of the body compared to the other side (hemihyperplasia)
• A birth defect of the abdominal wall where the intestines and other parts of the belly bulge into the umbilical cord at birth, called an omphalocele
• Diagnosis with a childhood embryonal cancer, most commonly Wilms tumor (of one or both kidneys) or hepatoblastoma
• Low blood sugar at birth due to excess insulin lasting more than a week
• Symptoms that suggest BWS along with a family history of BWS

Suspecting and diagnosing BWS early is important for starting cancer surveillance sooner.

Does Beckwith-Wiedemann syndrome (BWS) increase a person’s cancer risk?

Yes, BWS increases a person’s risk of childhood cancers called embryonal cancers. This includes Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma.

About 10% of children (1 in 10) with BWS will develop cancer. Cancers linked to BWS almost always occur in childhood. Early detection and treatment are important.

How is Beckwith-Wiedemann syndrome (BWS) managed and treated?

There is no cure for BWS, however regular check-ups and cancer testing in childhood may catch problems early, when treatment is more likely to be successful.

Management of BWS

Regular check-ups with a physical exam are recommended. Visits might include:

• Measuring and monitoring growth
• Checking blood pressure
• Watching for signs of low blood sugar
• Watching for problems with feeding, breathing or speech that might be caused by a large tongue
• Examining the abdomen (belly) for hernias or masses
• Cancer surveillance with blood and/or imaging tests

Cancer surveillance in children with BWS might include:

• Ultrasound: Baseline ultrasound of the abdomen (belly) with views of the liver, adrenal glands, and kidneys looking for enlarged organs or tumors is done at diagnosis or suspicion of BWS. Ultrasound imaging of the liver, adrenal glands and kidneys should continue every 3 months until age 4. From ages 4 to 7, children should have kidney ultrasound  every 3 months.
• Blood tests: Hepatoblastoma, a liver cancer of children, can produce high levels of alpha-fetoprotein (AFP). AFP testing is recommended every 3 months until age 4.
• Tests to detect neuroblastoma early in children with BWS caused by CDKN1C mutations, might be recommended as well.  

Treatment of BWS

There are no treatments specifically for children with BWS.

Symptoms of BWS, such as low blood sugar, abdominal wall defects, or trouble sleeping or eating related to a large tongue are managed in the same way as similar problems in children who do not have BWS.

Likewise, pediatric oncologists treat cancers associated with BWS the same as they would in children without BWS. Children with BWS may be eligible for clinical trials. Talk with your cancer treatment team to learn more about treatment options for your (child’s) specific cancer.

Questions to ask your doctor

If you or a family member has BWS, consider asking your doctor:

• What signs or symptoms should I watch for?
• What is my (child’s) risk of developing cancer?
• What can I do to lower my child’s risk of developing cancer?
• What cancer surveillance tests should I (my child) have?
• Should my family members get tested for BWS?