Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome occurring in approximately 1 in 14,000 births. BWS is characterized by large birth weights, an enlarged tongue, abdominal wall abnormalities and increased risk for certain types of childhood liver and kidney tumors.

Cause of Beckwith-Wiedemann Syndrome

Most cases of BWS occur sporadically, meaning that no other family members have a history of the condition. However, there are some instances in which BWS appears to run in families. Familial BWS may occur in up to 15% of cases. BWS also can be associated with assisted fertilization.

Most cases of BWS occur as a result of mutations in the short arm of chromosome 11. At least 5 different mutations have been identified, primarily involving IGF-2 and CDKN1-C, genes which control cell growth. However, in as many as 30% of BWS patients, genetic testing does not clearly identify any of the known genetic mutations. For this reason, BWS remains a condition that is most reliably diagnosed by examination of your child by an experienced physician familiar with the condition

Characteristic Traits

Children with BWS typically have some combination of the following characteristic features: large birth weight and length (overgrowth syndrome), enlarged tongue (macroglossia), abnormalities in tooth and jaw growth (malocclusion), abdominal wall defects (omphalocele or umbilical hernia), overgrowth of one side of the body (hemihypertrophy), ear grooves or pits and strawberry colored birthmarks of the forehead or eyelids (nevus flammeus). Each child with BWS is different, however, and your child may only have a few of these characteristic findings.

In addition to these common findings, approximately 1 in 10 children with BWS may develop certain kinds of liver tumors (hepatoblastomas) or kidney tumors (Wilm’s tumor). Of these, Wilm’s tumor is the most common tumor, occurring in 5-7% of children with BWS. Liver and kidney tumors may not be present at the time that your child is diagnosed with BWS. However, your child should be regularly screened for both of these tumors. Early detection of these fast-growing tumors leads to improved survival and better treatment.

Current tumor screening recommendations by the BWS foundation are summarized as follows:

• Hepatoblastoma screening: AFP, a blood marker for this type of tumor, should be checked every 6 weeks until 4 years of age. Your child should also have a liver ultrasound every 3 months until 4 years of age. Since the risk of hepatoblastoma drops after 4 years of age, both of these screening tests may be safely discontinued at that time.
• Wilm’s tumor screening: Your child should have kidney ultrasound to screen for Wilm’s tumor every 3-4 months until age 8. The vast majority of Wilm’s tumors in children with BWS occur by 4 years of age. However, there remains an elevated risk up until 8 years.

Most children undergo liver and kidney ultrasounds together until age 4. Afterward, screening ultrasounds focus primarily on the kidneys.

Diagnosis

The diagnosis of BWS is based on physical exam by a physician familiar with the syndrome followed by genetic (DNA) screening. Since every child is different, your child may not have all of the characteristic features. However, the presence of at least 2 of the most common characteristics is strongly suggestive of the diagnosis. There is no standardized genetic test that can detect BWS in every patient.

Surgical Treatment

Treatment of children with BWS is guided by which characteristics of the syndrome are present. Generally speaking, surgery may be required to correct the abdominal wall defect, reduce the size of the tongue or remove liver or kidney tumors.

Abdominal Wall Defect Surgery

Abdominal wall defects may be mild or severe. The mildest defects include umbilical or “belly-button” hernias and diastasis recti, which is widening of the space between the abdominal muscles. Diastasis recti generally requires no surgery and improves with age. Umbilical hernias may also resolve spontaneously over time. If they do not resolve, umbilical hernias may be repaired with a minor surgical procedure in early childhood.

Omphalocele is a more serious abdominal wall defect that occurs when children are born with a portion of the intestines or other abdominal organs outside the body. When present, omphalocele generally needs to be corrected surgically in the early days to weeks of life. This surgery is usually performed by a pediatric general surgeon.

Tongue Reduction Surgery

When children have BWS, they often have tongue enlargement (macroglossia) that prevents them from being able to keep their tongue in the mouth. As a result, the tongue frequently protrudes from the lips, and children may have problems with drooling, eating, speech and, in a minority, breathing. If the enlarged tongue is left untreated, children with macroglossia often develop abnormal tooth and jaw growth which requires a combination of orthodontics and jaw surgery in the teens for correction.

The purpose of tongue reduction surgery is to decrease the size of your child’s tongue thereby allowing your child to keep the tongue inside the mouth which can reduce drooling, assist eating, improve speech, aid breathing and prevent abnormal dental and jaw development. Our experience has shown that tongue reduction not only minimizes future tooth and jaw abnormalities, but also leads to improvement or normalization of existing deformities, especially when surgery is performed early.

Our center probably has the largest series of tongue reduction patients in the world (over 300 tongue reductions as of 2013). We typically perform tongue reduction surgery between 6-9 months of age. It may be performed as early as 3 months when there are airway concerns that might be improved by tongue reduction. Tongue reduction surgery performed before 2 years of age usually has a positive effect on the teeth and jaws. Tongue reduction surgery can be performed in older individual to assist orthodontic and surgical correction of tooth/jaw deformity.

Tumor Surgery

The timing and extent of surgery, and other malignancy treatments such as radiation and chemotherapy, required for treatment of hepatoblastomas or Wilm’s tumors is highly individualized depending on the extent of disease.