Beckwith-Wiedemann syndrome (BWS) is a growth disorder that can affect several parts of the body. Babies and children are larger than normal usually until age 8, when growth slows down, resulting in an average height in adults. Symptoms may include one side or area of the body growing more than the other side (asymmetric growth or hemihyperplasia), omphalocele or other abdominal wall defect at birth, low blood sugar (hypoglycemia) in infancy, an abnormally large tongue (macroglossia), abnormally large abdominal organs, creases or pits in the skin near the ears, and kidney abnormalities. Affected children have an increased risk to develop tumors, particularly a rare form of kidney cancer called Wilms tumor, a cancer of muscle tissue called rhabdomyosarcoma, and a form of liver cancer called hepatoblastoma. Some people only have one symptom while others may have many of the symptoms.

The cause of BWS is complex and is different for different people, but involves genes that control body growth. The genes, including the CDKN1C, H19, IGF2, and KCNQ1OT1 genes, are located on chromosome 11. In most cases BWS is caused by problems with the genomic imprinting of these genes. Genomic imprinting refers to having some genes that are active (expressed) only when inherited from the father and others that are active only when inherited from the mother. Less commonly, changes or mutations in the CDKN1C gene or larger changes to chromosome 11, such as a translocation, deletion, or duplication, may cause BWS.

Diagnosis of BWS is based on symptoms with the support of genetic testing. At present however, there is no clearly accepted diagnostic criteria as doctors are trying to understand the full spectrum of possible symptoms. While there is no cure for BWS, there are treatments available for many of the symptoms. Treatment may include medication for hypoglycemia, surgery to repair an omphalocele or other birth defect, or surgery to reduce size of the tongue (macroglossia repair). Early intervention, speech therapy, occupational therapy, and physical therapy may also be recommended. Evaluation by an orthopedic surgeon may be helpful depending on the areas of the body affected by overgrowth. Recommended management of BWS includes screening for the development of Wilms tumor, rhabdomyosarcoma, and hepatoblastoma.

Most cases of BWS are due to abnormalities involving genes on chromosome 11 that undergo genomic imprinting (imprinted genes). Normally, people inherit one copy of each chromosome from each parent, which also means that people normally inherit one copy of each gene (on the chromosomes) from each parent. Most genes on chromosome 11 have both copies activated (expressed). However, for some of these genes, only the paternal copy (inherited from a person's father) is expressed, or only the maternal copy is expressed. These parent-specific differences in gene expression are due to what is known as genomic imprinting.

The genetic imprinting results from changes produced in a process called methylation (in about 50% of the cases), a chemical reaction that occurs when egg and sperm cells are formed, and which attaches molecules called "methyl groups" to specific pieces of DNA, inactivating a specific gene, paternal or maternal. SBW is often associated with changes in regions of DNA on chromosome 11 called imprinting centers (IC1 and IC2), which control the methylation of several genes involved in normal growth. Abnormal methylation disrupts the regulation of these genes, leading to overgrowth and the other features of BWS. The genes affected include the CDKN1C, H19, IGF2, and KCNQ1OT1 genes.

About 20% of cases of BWS are caused by a genetic abnormality called paternal uniparental disomy (UPD), in which both copies of chromosome 11 are inherited from the father and no copy is inherited from the mother. Paternal UPD usually occurs early in embryonic development, affecting only some of the body's cells (called mosaicism). Mosaic paternal UPD leads to an imbalance of the active genes on chromosome 11, causing the symptoms of the syndrome.

Less commonly, BWS may be caused by mutations in the CDKN1C gene, which gives instructions for making a protein that helps control growth before birth. Mutations in this gene prevent the protein from restricting growth, leading to the features of BWS.

More rarely, in about 1% of people with BWS have a chromosome abnormality, such as a translocation, duplication, or deletion of genetic material on chromosome 11 (the 11p15 region).

Because the genetic changes responsible for BWS are very complex, people with questions about the causes and inheritance of BWS should consult with a genetics professional.

Most cases of Beckwith-Wiedemann syndrome are caused by abnormal regulation of imprinted genes in the BWS critical region (IC1 and IC2) on chromosome 11p15.5 caused by one of several genetic mechanisms.

About 10% to 15% of affected people are part of families with more than one affected person. In most of these families, the condition appears to be inherited in an autosomal dominant manner.[9530 This means that having only one changed (mutated) copy of the responsible gene in each cell is enough to cause symptoms of the disorder. In most of these cases, the affected person inherits the genetic change from their mother. In some cases, a person inherits the mutated gene but does not have symptoms of the disorder.

Rarely, BWS results from abnormalities of the structure of chromosome 11. Some of these chromosome abnormalities are inherited from a parent, while others occur randomly during the formation of eggs and sperm, or very early in fetal development.

The risk to the brothers and sisters of a child with BWS depends on the genetic basis for BWS in this child. The majority of families have a recurrence risk of less than 1%; however, as commented before, in some families the recurrence risk as high as 50%. In order to better assess the recurrence risk for BWS in a family, the underlying cause needs to be identified. Due to the complexity of the genetics, it is recommended that any determination of recurrence risk for the parents or adults with BWS or testing of relatives to be performed by a genetics health care professional.

• Large tongue
• Abdominal wall defect (weakness in the stomach wall near the umbilical cord)
• Overgrowth on one side of the body
• A specific type of kidney tumor (Wilms tumor)
• Abnormal level of insulin in the blood

Other features may include:

• Large birth weight
• Pink or red facial birthmarks (angel kiss or stork's bite)
• Ear creases or pits
• Low blood sugar that lasts less than a week
• Enlarged liver or kidneys
• Umbilical hernia