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What is Beckwith-Wiedemann syndrome?
Beckwith-Wiedemann syndrome (BWS) is a growth regulation disorder.
The most common features of BWS include macrosomia (large body size),
macroglossia (large tongue), abdominal wall defects, an increased risk
for childhood tumors, kidney abnormalities, hypoglycemia (low blood
sugar) in the newborn period, and unusual ear creases or pits. Children
with BWS may also have hemihyperplasia, in which some parts of the body
are larger on one side than on the other.
The major features of BWS, macrosomia and macroglossia, are often
present at birth. Abdominal wall defects such as omphalocele, which
causes the inside of the abdomen to protrude through the navel, are also
present at birth and may require surgery before an infant leaves the
hospital. Mothers of children with BWS may have pregnancy complications,
including premature delivery and polyhydramnios (excess amniotic
fluid). An unusually large placenta and long umbilical cord may also be
present.
The increased growth rate generally slows during childhood.
Intellectual development is usually normal, and adults with BWS
typically do not experience any medical problems related to their
condition.
What causes BWS?
BWS is a genetic condition related to changes in the genes (in an
area called the short arm) of chromosome 11 (11p15.5). This is the area
of the chromosome where two genes are located: insulin-like growth
factor II (IGF-2) and cyclin-dependent kinase inhibitor (CDKN1C). In
most cases (about 85%), the genetic changes that cause BWS happen
sporadically (occurs by chance) in families where there is no history of
the condition. In about 10% to 15 % of cases, the genetic changes may
be inherited. This means that the risk for BWS can be passed from
generation to generation in a family. The genetic mechanisms that cause
gene mutations (alterations) resulting in BWS are complex.
How is BWS inherited?
The 10% to 15% of BWS that is inherited follows an autosomal dominant
inheritance pattern. Normally, every cell has two copies of each gene:
one inherited from the mother and one inherited from the father. In
autosomal dominant inheritance, a mutation happens in only one copy of
the gene. This means that a parent with a gene mutation may pass along a
copy of their normal gene or a copy of the gene with the mutation.
Therefore, a child who has a parent with a mutation has a 50% chance of
inheriting that mutation. A brother, sister, or parent of a person who
has a mutation also has a 50% chance of having the same mutation.
How common is BWS?
BWS has been found across different population groups. Approximately
one in 13,700 people have BWS. Some researchers believe this number
could be an underestimate.
How is BWS diagnosed?
The diagnosis of BWS is clinical, meaning that it is based primarily
on physical features. BWS is suspected in children who are larger than
expected for their age, especially if growth is not symmetrical (the
same on both sides). An enlarged tongue and abdominal wall defect,
primarily omphalocele, are also considered to be common features. There
are many other features that may be seen in some children with BWS.
However, not every child with BWS will have every feature. Features are
listed as major (common) or minor (less common). It is generally agreed
that at least one major feature and two minor features are required for a
diagnosis of BWS:
Major Features
- Macrosomia (large body size)
- Macroglossia (large tongue)
- Omphalocele (abdomen protrudes through navel)
- Hemihyperplasia (some parts of the body are larger on one side)
- Ear lobe creases or pits
- Visceromegaly (enlargement of one or more abdominal organ)
- Embryonal tumor (Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma)
- Adrenocortical tumor (adrenal gland tumor)
- Kidney abnormalities
- Cleft palate (gap in the roof of the mouth)
- Family history of BWS
Minor Features
- Polyhydramnios (excessive amniotic fluid)
- Prematurity (low birth weight)
- Hypoglycemia (low blood sugar)
- Advanced bone age
- Heart problems
- Diastatsis recti (separation of the right and left sides of the main abdominal muscle)
- Hemangioma (noncancerous tumor made up of blood vessels)
- Facial nevus flammeus (hemangioma of the skin, also called a “port-wine stain”)
- Characteristic facial features
- Identical twins
Genetic testing for gene mutations associated with BWS is
available, but it is complex. It is recommended that all families
considering genetic testing for BWS meet with a clinical geneticist (a
medical doctor who has training in genetics) and genetic counselor that
can explain the tests and coordinate testing. The genetic testing
methods that are currently available may be able to identify up to 80%
of genetic mutations causing BWS.
What are the estimated cancer risks associated with BWS?
The estimated risk for a tumor in a child with BWS is about 7.5%.
Tumors are very rare after age 10, and the risk for an individual tumor
decreases over time until the risk is similar to that of the general
population. The cancer risk is highest in children with BWS who have
hemihyperplasia and organomegaly (enlargement of organs), especially
nephromegaly (enlargement of the kidneys) than in children with isolated
hemihypertrophy. Several different tumor types, both cancerous and
benign (noncancerous), have been reported in children with BWS. The most
common tumor types are:
- Wilms tumor (kidney tumor; about 40% of cases)
- Hepatoblastoma (liver tumor)
- Adrenocortical carcinoma (about 20% of cases)
- Neuroblastoma
- Rhabdomyosarcoma
What are the screening options for BWS?
Screening recommendations for patients with BWS are aimed primarily
at detecting hepatoblastoma and Wilms tumor. Current suggested
screenings for people who are known or suspected to have BWS include:
- Baseline magnetic resonance imaging (MRI) or computed tomography (CT or CAT) scan of the abdomen at the time of diagnosis
- Abdominal ultrasound to screen for hepatoblastoma and Wilms tumor every three months, until age 8. After age 8, imaging may be limited to just a renal ultrasound
- Serum alpha-fetoprotein blood test every six weeks (every three months at the minimum), until age 4
- Regular physical examination, including abdominal exam; schedule determined by your doctor
If a child has an identical twin who doesn’t have signs of BWS,
the twin should still be screened with ultrasounds and serum
alpha-fetoprotein blood tests, as noted above.
Additionally, screening for hypoglycemia is important in infancy.
Children with BWS may also need to be evaluated by a craniofacial team
(doctors who specialize in treating head and face conditions) to
determine if surgery may be required to decrease tongue size. Support
may be needed to assist with feeding difficulties in infancy and speech
development in childhood. Children with significant hemihyperplasia may
need to be evaluated by an orthopedist (bone doctor).
Screening recommendations may change over time as new technologies
are developed and more is learned about BWS. It is important to talk
with your doctor about appropriate screening tests.
Learn more about what to expect when having common test, procedures, and scans.
Questions to ask the doctor
If you are concerned about the risk for cancer in your child, talk to
your doctor. Consider asking the following questions of your doctor:
- What is my child’s risk of developing cancer?
- What can I do to reduce my child’s risk of cancer?
- What are my options for cancer screening?
If you are concerned about your family history and think that
you, your child, or other family members could have BWS, consider asking
the following questions:
- Does our family history increase my child’s risk of developing cancer?
- Could my family have BWS?
- Should I meet with a genetic counselor?
- Should I consider genetic testing?
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