Beckwith-Wiedemann Syndrome

  • What is Beckwith-Wiedemann syndrome?

    Beckwith-Wiedemann syndrome (BWS) is a genetic disorder commonly characterized by overgrowth. The disorder's severity varies widely in children. Patients usually come to medical attention because they are born with several features that occur together. However, few children have all the characteristics associated with the syndrome. Some of the features in BWS patients include:

    • Large birth weight and length overgrowth of one side of the body (hemihypertrophy). The overgrowth may be limited to a portion of the body, such as the legs, or it may involve several different areas of the body, including the arms, face and tongue. A discrepancy in the length and/or thickness of one leg compared with the other is the most common presentation of hemihypertrophy. Hemihypertrophy can occur by itself, in which case it is called "isolated," or it can be one of several characteristics of BWS or another genetic syndrome. Sometimes hemihypertrophy is not noticed at birth but becomes apparent as children grow.
    • An enlarged tongue (macroglossia).
    • Low levels of sugar in bloodstream (hypoglycemia) during the newborn period.
    • Defects in the abdominal wall (such as omphalocele, umbilical hernia).
    • Enlarged abdominal organs, such as the kidneys, liver and pancreas.
    • Pits or creases in the earlobe or behind the ear.
    • An increased risk of developing certain cancers during childhood (most of these cancers can be cured with proper treatment).

    Beckwith-Wiedemann syndrome occurs in 1 in 14,000 births, with about equal incidence in boys and girls. Because children who have milder cases of the syndrome may never receive a diagnosis of BWS, this figure may be an underestimation.

  • Causes

    Scientists believe Beckwith-Wiedemann syndrome and isolated hemihypertrophy result from alterations in the expression of one or more genes in children. Still, the genetics of these conditions are complex, and researchers don't yet completely understand them. While some cases are inherited from a parent, most cases occur as new genetic abnormalities only within the affected child.

    Sporadic BWS and hemihypertrophy

    The majority of BWS cases — up to 85 percent — are sporadic, or occur by chance, without a family history of the condition. The majority of these sporadic cases are associated with genetic abnormalities on a region of chromosome 11. Scientists believe the overgrowth associated with Beckwith-Wiedemann Syndrome and hemihypertrophy may develop because of improper inactivation of one or more growth-suppressing genes, or because of overexpression of genes that encourage cell growth. 

    Since sporadic BWS and isolated hemihypertrophy are not inherited, people with these syndromes are not likely to pass them on to their children. In addition, the parents of children with sporadic BWS or isolated hemihypertrophy are not at increased risk of having other children with these disorders.

    Inherited BWS or isolated hemihypertrophy

    Approximately 10 to 15 percent of BWS or hemihypertrophy cases are hereditary, meaning they may be passed through generations. In these cases, there is up to a 50 percent risk that an affected parent will pass on the abnormal gene to a child during pregnancy. Most hereditary cases are associated with a mutation in a gene on chromosome 11.

    Fewer than 1 percent of hereditary cases are due to a different type of abnormality on the same chromosome, a rearrangement of genetic material known as a "translocation" or an "inversion." These involve the detachment and rearrangement of chromosomes. Translocations and inversions cause problems if the breakpoints interrupt important genetic functions, or if pieces of the chromosome break off and become lost. 

    Because some children with isolated hemihypertrophy may have the same genetic alterations as those observed in patients with Beckwith-Wiedemann syndrome, all children with hemihypertrophy should receive an evaluation from a geneticist to establish a correct diagnosis. Geneticists can also assist with referrals to other specialists, such as orthopedic surgeons, who can help manage limb-length discrepancies; and oncologists, who can discuss cancer risks and coordinate and review the results of appropriate tests for cancer screening.

  • Genetic testing

    Genetic testing can confirm a suspected diagnosis of Beckwith-Wiedemann syndrome or isolated hemihypertrophy. Genetic testing also may help to determine whether, and how, these disorders occur within a family, which will provide information about the chance for recurrence in other children. Genetic testing for these disorders requires collecting a blood sample. 

    In many cases, genetic testing can help explain the cause of BWS or isolated hemihypertrophy. However, a normal result from genetic testing does not rule out the diagnosis of these disorders. Some of the genetic causes of BWS and isolated hemihypertrophy are still unknown, so it isn't possible to test for them all.

    For that reason, we recommend that children who have features consistent with a clinical diagnosis of BWS or isolated hemihypertrophy — but who receive negative genetic test results — receive the same medical management as children who have a confirmed genetic diagnosis.

  • Cancer risk

    Wilms' tumor, a cancer of the kidney, is the most common cancer in children with BWS or isolated hemihypertrophy. Most children with this cancer develop it before age 5, but some children can develop it later. Ninety five percent of Wilms' tumors occur in patients with BWS or hemihypertrophy by age 8. 

    Hepatoblastoma, a cancer of the liver, is the second most common cancer in patients with BWS or isolated hemihypertrophy. This cancer usually develops by 2 years of age. 

    Rarely, patients with BWS or isolated hemihypertrophy develop other cancers.

    Cancer screening

    Wilms' tumor and hepatoblastoma are cancers that can be cured with proper treatment. The probability of cure depends, in part, upon the cancer's stage, or extent of spread, at diagnosis. We recommend patients with Beckwith-Wiedemann syndrome or isolated hemihypertrophy have regular screenings in order to detect potential cancers as early as possible.

    Research shows early detection leads to improved outcomes, because cancers are often smaller and easier to remove surgically. An earlier diagnosis may also reduce the need for chemotherapy and lower the dose of, or eliminate the need for, radiation treatment.

    All cancer screenings should be performed in consultation with a pediatric oncologist, and radiology studies should be reviewed by a radiologist with pediatric expertise. Whenever possible, cancer screening should be done at the same center for consistency of results. In the event that screening results in a suspected or confirmed tumor, we recommend a prompt referral to a pediatric oncologist. 

    We recommend the following cancer screening protocol for patients suspected of having, or proven to have, Beckwith-Wiedemann syndrome or isolated hemihypertrophy:

    Abdominal ultrasound

    An abdominal ultrasound examination should be performed every three months until 8 years of age. Until 4 years of age, the ultrasound should include views of the liver, kidneys and other internal organs.

    Because the risk for hepatoblastoma drops markedly after this age, the remaining ultrasounds can focus specifically on the kidneys. Abdominal ultrasounds are safe and painless, and they do not involve the use of radiation.

    Measurement of blood alpha-fetoprotein (AFP) concentration

    A blood test to measure serum AFP should be performed every six weeks until 4 years of age. AFP is released by hepatoblastoma tumors and can be a highly sensitive way to detect these cancers. Because AFP levels are normally high during the newborn period, measurements should be performed regularly and reviewed by an experienced pediatrician or pediatric oncologist.

  • Long-term development

    Almost all children with Beckwith-Wiedemann syndrome and isolated hemihypertrophy grow up to be healthy adults. By adolescence, growth tends to normalize and cancer risk decreases. Adults with these disorders may hold successful careers and have healthy children. They typically have normal intelligence and normal lifespans, and they are capable of leading successful, happy and fulfilling lives.

    The physical features of BWS often become less noticeable as children age. For example, children with BWS are often larger than their peers during childhood, but their growth slows as they get older, and they generally grow to be adults of average height. 

    Some of the visible, physical signs of BWS, such as a disparity in leg length or an enlarged tongue, may require surgical correction, but most of the characteristics decrease with time. 

    Additional healthcare needs

    Some children with Beckwith-Wiedemann syndrome and isolated hemihypertrophy may need to see other medical specialists. For example, children with leg-length discrepancies may require evaluation by an orthopedist. Other areas of specialty care include oncology, plastic surgery and genetics.

Reviewed by Kim E. Nichols, MD, Kristin Zelley, MS on January 03, 2011