Beckwith-Wiedemann Syndrome

What is Beckwith-Wiedemann syndrome?

Beckwith-Wiedemann syndrome is a genetic disorder commonly characterized by overgrowth. The severity of this disorder varies widely in children and is usually recognized at birth, when a child is born with several features of Beckwith-Wiedemann syndrome. However, few children have all the associated characteristics. Some may have only a single, subtle feature, such as isolated hemihypertrophy of a limb (also known as hemihyperplasia). 

Beckwith-Wiedemann syndrome occurs in approximately 1 in 11,000 births, with about equal incidence in boys and girls. However, because children who have milder cases of the syndrome may never receive a diagnosis of Beckwith-Wiedemann syndrome or 11p overgrowth spectrum, this figure may be an underestimation.

Signs and symptoms

The whole range of physical features associated with Beckwith-Wiedemann syndrome are part of the 11p overgrowth spectrum. The 11p overgrowth spectrum is defined as overgrowth and other features associated with genetic changes at a specific chromosomal region known as 11p, the same region that causes Beckwith-Wiedemann syndrome.

The features of Beckwith-Wiedemann syndrome include:

  • Large birth weight and length (macrosomia)
  • Overgrowth of one side or one part of the body (hemihypertrophy/hemihyperplasia))
  • An enlarged tongue (macroglossia).
  • Low levels of sugar in bloodstream (hypoglycemia) during the newborn period and sometimes prolonged hypoglycemia (due to hyperinsulinism).
  • Defects in the abdominal wall (such as umbilical hernia or an omphalocele, where the intestines and sometimes other abdominal organs protrude from the abdominal wall outside the body)
  • 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 which can be cured with proper treatment).

Beckwith-Wiedemann syndrome occurs in 1 in 11,000 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.


There are several known genetic causes of Beckwith-Wiedemann syndrome and isolated hemihypertrophy, which generally result in changes in the expression of one or more of the genes at a region of chromosome 11 known as 11p15.

In most cases, these genetic changes occur in some but not all of the cells, resulting in mosaicism. Mosaicism means that some parts of the body have cells with normal chromosome 11 and other parts have cells with changes on chromosome 11. This heterogeneity leads to the spectrum of clinical features seen in Beckwith-Wiedemann syndrome and hemihypertrophy referred to as the 11p overgrowth spectrum.

Normally, people have two copies of chromosome 11, one inherited from their mother and one from their father. The maternal copy of chromosome 11 will express some genes that control growth on chromosome region 11p15 that the paternal copy does not, and vice versa. This phenomenon is called imprinting, and is caused by methylation, or a process of marking the DNA to turn certain genes on or off. The balance of gene expression from the maternal and the paternal copies are what produce normal, symmetric growth. 

However, in patients with Beckwith-Wiedemann syndrome, different parts of this process can be changed.

Possible causes for Beckwith-Wiedemann syndrome are: 

  • Methylation defects at chromosome 11p15: Methylation defects could add or delete a mark, which would result in a gene being “turned on” when it should be “turned off,” or “off” when it should be “on.” 
  • Uniparental disomy (UPD) at chromosome 11p15: UPD occurs when both copies of 11p15 are inherited from only one parent. In cases of UPD in Beckwith-Wiedemann syndrome, both copies of chromosome 11p15 are inherited from the father (paternal UPD). In these cases, the patient expresses only the genes from the father’s chromosome without being counterbalanced by the mother’s.
  • Alterations, known as mutations, of the CDKN1C gene, or rarely the regions where methylation marks are made, can occur.
  • Chromosomal abnormalities at 11p15: These changes can include deletions (missing genetic material), duplications (extra genetic material), translocations (genes in the wrong place) and inversions (rearranged genetic material).  

While some cases are inherited from a parent, most cases occur as new genetic abnormalities only within the affected child. 

Sporadic Beckwith-Wiedemann syndrome and hemihypertrophy

Up to 85 percent of Beckwith-Wiedemann syndrome and hemihypertrophy cases are sporadic, meaning they occur by chance and without a family history of the condition. The majority of these sporadic cases are associated with genetic abnormalities on a region of chromosome 11. It is presumed that the overgrowth associated with Beckwith-Wiedemann syndrome and hemihypertrophy may develop because of improper inactivation of one or more growth-suppressing genes, or, alternately, because of overexpression of genes that encourage cell growth. 

Individuals with sporadic Beckwith-Wiedemann syndrome and isolated hemihypertrophy are not likely to pass these conditions on to their children. Parents of children with sporadic Beckwith-Wiedemann syndrome 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 Beckwith-Wiedemann syndrome or hemihypertrophy cases are hereditary, meaning they may be passed from parents to children. In these cases, there is up to a 50 percent chance that an affected or carrier parent will pass on the genetic abnormality to a child during pregnancy.

Most hereditary cases are associated with a mutation in a gene on chromosome 11 known as CDKN1C. Less than 1 percent of Beckwith-Wiedemann syndrome 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 often involve the detachment and rearrangement of parts of chromosomes. Translocations and inversions can cause additional problems if the places where the chromosomes break (breakpoints) interrupt important genes, or if pieces of the chromosome break off and become lost. 

Diagnosis and genetic testing

The diagnosis of Beckwith-Wiedemann syndrome and hemihypertrophy are clinical diagnoses, meaning the diagnosis is made when a child has some or all of the physical features associated with the condition. A clinical diagnosis can often be confirmed by genetic testing, which can often explain the cause of Beckwith-Wiedemann syndrome or isolated hemihypertrophy.

Because hemihypertrophy can present either as an isolated condition, or as a feature of Beckwith-Wiedemann syndrome, all children with hemihypertrophy should seek an evaluation from a geneticist to establish a correct diagnosis. Genetic testing also may help to determine whether, and how, these disorders occur within a family, which would provide information about the chance for recurrence in other children. Testing for these disorders requires collecting a blood sample or other tissue samples (usually DNA from blood cells). 

A normal genetic test result does not rule out the diagnosis of these disorders. The normal result could be due to mosaicism, so that the genetic change leading to Beckwith-Wiedemann syndrome was not present in the tissue tested. It is recommend that additional tissue be collected from patients with suspected Beckwith-Wiedemann syndrome, in conjunction with other surgical procedures when possible, so further testing can be done.

Experts at CHOP recommend that children who have features consistent with a clinical diagnosis of Beckwith-Wiedemann syndrome or isolated hemihypertrophy — but who receive negative genetic test results — receive the same medical management and cancer surveillance protocol as children who have a confirmed genetic diagnosis.

Cancer risk

Children with Beckwith-Wiedemann syndrome and isolated hemihypertrophy are at an increased risk of developing certain cancers during childhood. The risk of developing cancer is estimated to be 5 to 10 percent, but that risk may vary depending on the specific genetic cause of the child’s condition.

  • Wilms' tumor, a cancer of the kidney, is the most common cancer found in these children. Ninety five percent of Wilms' tumors occur in Beckwith-Wiedemann syndrome or hemihypertrophy patients by age 7. 
  • Hepatoblastoma, a cancer of the liver, is the second-most common cancer in patients with Beckwith-Wiedemann syndrome or isolated hemihypertrophy. This cancer usually develops by 2 years of age. 
  • Rarely, adrenocortical carcinoma, neuroblastoma or rhabdomyosarcoma.


Cancer screening and follow-up care

We recommend that patients with Beckwith-Wiedemann syndrome or isolated hemihypertrophy have regular screenings in order to detect potential cancers as early as possible. Wilms' tumor and hepatoblastoma are cancers that can be cured with proper treatment. The probability of cure depends in part upon the extent of the cancer’s spread (its stage) at diagnosis, as well as its histology or acquired genetic changes in the tumor tissue. Research shows that early detection leads to improved outcomes, as tumors are then 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 screening should be performed in consultation with a pediatric geneticist or oncologist, and radiology studies should be reviewed by a radiologist with pediatric expertise. In the event that screening results in a suspected or confirmed tumor, we recommend a prompt referral to a pediatric oncologist.

CHOP recommends 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 should be performed every three months until 7 years of age. Until 4 years of age, the ultrasound should include views of the liver, kidneys and other internal organs. After 4 years of age, renal ultrasounds with views of the adrenal glands should be performed until 7 years of age.

The risk for hepatoblastoma drops significantly in children older than 4, so the remaining ultrasounds can focus specifically on the kidneys (renal ultrasounds), which includes the adrenal glands that sit on top of the kidneys.

Abdominal ultrasounds are safe and painless, and 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 three months until 4 years of age. AFP is a protein released by immature or damaged liver cells, and it is released at higher levels by hepatoblastoma tumor cells. This is an extremely 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, geneticist or pediatric oncologist.

The key with AFP levels is to follow the trend — normal levels are expected to decrease over time. Whenever possible, AFP screening should be done at the same center for consistency of results. 

Additional healthcare needs

Some children with Beckwith-Wiedemann syndrome and isolated hemihypertrophy may need to see other medical specialists. Geneticists can also assist with referrals to these specialists and aid in monitoring tumor screening.

  • Oncology: Oncologists can discuss cancer risks, as well as coordinate and review the results of appropriate tests for cancer surveillance.
  • Orthopaedics: Children with leg-length discrepancies may require evaluation by an orthopedist.
  • Plastic surgery: Children with enlarged tongues should be evaluated by a plastic surgeon and have formal evaluations for potential effects on feeding, speech and sleep.
  • Endocrinology: Children with severe hypoglycemia should be evaluated by an endocrinologist, and treatment may be required until this normalizes.

Additional evaluations are based on clinical needs.


Most children with Beckwith-Wiedemann syndrome and isolated hemihypertrophy grow up to be healthy adults.

The physical features of Beckwith-Wiedemann syndrome often become less noticeable as children grow. They are often larger than their peers during childhood, but their growth slows as they get older. By adolescence, growth tends to normalize and cancer risk decreases. They generally grow up to be adults of above average height. 

Adults with these disorders can lead a normal life and have healthy children. They typically have normal intelligence and normal lifespans. Some of the visible, physical signs of Beckwith-Wiedemann syndrome, such as a disparity in leg length or an enlarged tongue, may require surgical correction, but most of the characteristics become less apparent with time. 

Support and information resources

Research: for more information about the Beckwith-Wiedemann syndrome registry/repository, please contact

Reviewed by Jennifer M. Kalish, MD, PhD, Kristin Zelley, MS, LCGC, Garrett M. Brodeur, MD

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