Beckwith-wiedemann syndrome

Beckwith-Wiedemann syndrome may be suspected in children who were born larger than normal (macrosomia), with a birth defect where there is an outpouching of abdominal contents into the belly button (umbilical hernia or omphalocele) or who have a large tongue (macroglossia). As the child ages and certain parts of their body grow faster than others (hemihyperplasia), Beckwith-Wiedemann syndrome may be suspected. The condition also might be suspected in a child who has a close relative with Beckwith-Wiedemann syndrome, especially if the child has any of the common features of this condition.

Most people with Beckwith-Wiedemann syndrome are the only person in their family to have the condition. If certain genetic changes have been identified in an affected individual, then the parents of the person should also be tested even if they do not appear to have the condition. In order to determine if other family members, including parents of an affected individual, should be tested for Beckwith-Wiedemann syndrome, it would be helpful to meet with a medical geneticist or a genetic counselor to discuss these matters further. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

The largest support network for Beckwith-Wiedemann Syndrome is located in the United Kingdom and is known as the Beckwith-Wiedemann Syndrome Support Group. There is a great deal of information about the condition as well as stories of families who have children with this disorder. Social media sites such as Facebook (www.facebook.com) can also be a great resource for finding other families of children with Beckwith-Wiedemann syndrome. There is at least one, large active support group on Facebook for Beckwith-Wiedemann syndrome which can be found here. Finally, the organization Making Contact can help connect families who have children with Beckwith-Wiedemann syndrome with other families.

Clinical research trials involving Beckwith-Wiedemann syndrome can be found by searching “Beckwith-Wiedemann syndrome” on ClinicalTrials.gov..

The common abbreviation for Beckwith-Wiedemann syndrome is BWS.

The average life expectancy for people with Beckwith-Wiedemann syndrome is usually normal. The only life-threatening symptoms of Beckwith-Wiedemann syndrome occur in childhood and include low blood sugar (hypoglycemia) and tumors. Rarely, these may lead to early death; however, with proper medical management, most individuals with Beckwith-Wiedemann syndrome will have a normal lifespan.

Beckwith-Wiedemann syndrome is a genetic overgrowth syndrome that can affect multiple parts of the body. Infants with the condition are usually bigger than other infants (macrosomia) and tend to be taller than their classmates during childhood. Some children with Beckwith-Wiedemann syndrome will have specific parts of their body on one side of the body or the other that will grow abnormally large making them look uneven. This uneven growth (hemihyperplasia) usually becomes less obvious as the child gets older.

Beckwith-Wiedemann syndrome (BWS) can cause low blood sugar that should be monitored and treated to reduce the risk of damage to the central nervous system. About 10% (1 in 10) of people with BWS will develop cancerous or non-cancerous tumors, especially a form in the kidney known as Wilms tumor and a form in the liver called hepatoblastoma. These tumors most often appear during childhood. The overly large tongue (macroglossia) can cause problems feeding, swallowing, or breathing when the child is still young. There is a risk of scoliosis in individuals with Beckwith-Wiedemann syndrome that have hemihyperplasia. Hemihyperplasia describes a situation where specific parts of the body or one side of the body grows abnormally large making the parts or sides of the body look uneven. Hemihyperplasia is only present in a small percentage of individuals with Beckwith-Wiedemann syndrome; therefore, the overall risk of scoliosis with this disorder is low.

Beckwith-Wiedemann has several different genetic causes. The condition is most often caused by abnormal regulation of genes on chromosome 11. People usually receive two copies of chromosome 11 – one from each parent. Both copies of the genes on chromosome 11 are usually "turned on" or activated. However, there are some genes on chromosome 11 in which only the copy received from dad is turned on (paternally inherited copy) or only the copy received from mom is turned on (maternally inherited copy). A process called genomic imprinting oversees this. When this process goes wrong on chromosome 11, Beckwith-Wiedemann syndrome can occur.

About 50% of cases of Beckwith-Wiedemann syndrome are caused by errors in methylation. Methylation can be thought of as putting a flag on an area of DNA. In genes that go through genomic imprinting, these flags can help identify which parent the gene originated from. There are areas of chromosome 11 known as imprinting centers (ICs), which are in charge of putting these flags on genes that are responsible for controlling growth. When these centers can’t put the flags in the correct places, the genes don’t work correctly and overgrowth can occur.

About 20% of cases of Beckwith-Wiedemann syndrome are caused when a person has two active copies of the paternally inherited genes. This can occur early in development and only affect some of the body’s cells resulting in certain areas of abnormal growth.

Sometimes changes in the CDKN1C gene, which is responsible for making a protein that controls growth before birth, can cause Beckwith-Wiedemann syndrome. Changes in this gene prevent it from restricting growth causing the abnormal growth seen in the condition.

We all have differences in the way our genes are spelled (gene variants). In many cases, these spelling changes do not appear to change the protein that the gene produces and therefore do not seem to lead to any health or developmental problems. Some changes, though, can alter the way a gene works, leading to an abnormal protein product being made. When this happens, a disease can occur. Disease-causing gene changes are known as mutations. There are several genetic changes and mutations that have been identified in genetic regions associated with Beckwith-Wiedemann syndrome that are known to cause the disorder. In other cases, however, a "variant" or "variant of unknown significance" is found in those genetic regions, the effect of which, if any, is unknown.

When a person who is suspected to have Beckwith-Wiedemann syndrome has genetic testing and a variant in one of those genetic regions is found, we can not be sure whether that change is the cause of the symptoms that person has. If the person had enough symptoms to allow for the diagnosis of Beckwith-Wiedemann syndrome to be made clinically, the finding of a variant will likely not lead to the doctor changing or removing the diagnosis. Over time, as more people have genetic testing for Beckwith-Wiedemann syndrome, unclear gene variants may be reclassified as disease-causing if identified in enough affected individuals.

It is also possible that a person with signs of Beckwith-Wiedemann syndrome but with only a variant identified on genetic testing may have a change or changes in other genes that have not yet been identified as being associated with Beckwith-Wiedemann syndrome. Over time, we may identify more genes that cause Beckwith-Wiedemann syndrome, leading to more extensive genetic testing for this condition to be possible.

The main symptoms of Beckwith-Wiedemann syndrome include birth height and weight greater than 97% of other babies (macrosomia); indentations or creases in the skin near the ears (ear pits); a large tongue (macroglossia), a problem with the abdominal wall causing the intestines, liver, and sometimes other organs to remain outside of the abdomen in a sac (omphalocele) or a small outpouching at the belly-button (umbilical hernia); specific types of childhood tumors in the kidney or liver (embryonal tumors); and low blood sugar in the first few months of life (hypoglycemia).

Most people who have one of the gene changes associated with Beckwith-Wiedemann syndrome will shows signs of the disorder. This means that the penetrance of the disorder is quite high. Nonetheless, some individuals even within the same family may have milder signs, making the diagnosis less obvious. When different individuals with the same condition show different signs or have different severity of certain symptoms, this is known as variable expression. It is recommended that relatives of individuals with Beckwith-Wiedemann syndrome who are also at risk for the disorder based on the specific way in which it is being passed in that family have a formal evaluation with a geneticist to look for signs of the condition. This is particularly important because the genetics of Beckwith-Wiedemann syndrome are complicated. A geneticist or a genetic counselor can help families understand who else is at risk in their family and therefore who should be evaluated. TGenetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

As of June 2019, Beckwith-Wiedemann syndrome is not on the Recommended Uniform Screen Panel (RUSP). The RUSP is created by the Health Resources and Services Administration, and states use this list to guide what conditions they screen for on newborn screening.

Because there are several different genetic causes of Beckwith-Wiedemann syndrome, there are several different genetic tests that may be performed to diagnose the condition. The most common genetic tests include:

As of June 2019, there were studies listed at ClinicalTrials.gov either ongoing or recruiting that are looking at certain aspects of Beckwith-Wiedemann syndrome. You can check this website to see current clinical trials.

Following diagnosis of Beckwith-Wiedemann syndrome, if the child has an abnormally large tongue (macroglossia) it is recommended that their airway be evaluated to make sure that it is not being negatively affected. A feeding specialist may be needed if the macroglossia seems to be affecting the child’s ability to eat. Also, a child may have sleep apnea that will need to be treated by a sleep specialist. A pediatric endocrinologist may need to follow the child if the low blood sugar (hypoglycemia) lasts longer than the first few days of life. An ultrasound of the kidneys is recommended yearly from the age of 8 years until mid-adolescence and, if abnormal, referral to a doctor who is a kidney specialist (nephrologist). If a heart abnormality is suspected then a cardiac evaluation by a doctor specializing in the heart (cardiologist) may be recommended.

There is a very specific protocol for screening for tumors in infants and children with Beckwith-Wiedemann syndrome. This involves an abdominal ultrasound every three months until the child reaches the age of 8 years old as well as a blood test every 2-3 months for the first four years of life. This blood test measures a protein known as AFP. AFP levels are higher in the blood of people with one of the tumors associated with Beckwith-Wiedemann syndrome, a liver tumor known as hepatoblastoma.

If an individual has Beckwith-Wiedemann syndrome caused by either a gain or loss of methylation at imprinting center 1 or 2 (IC1 or IC2, respectively), then the chance of having a child with the condition is relatively low.

If an individual has Beckwith-Wiedemann syndrome due to a change in the CDKN1C gene then the chance of having a child with the condition depends on the affected person’s gender. If the affected individual is female, then her chance of having a child with the condition is 50%. If male, then the chance is lower than 50% with the exact risk being unknown.

If an individual has Beckwith-Wiedemann syndrome due having two copies of the paternally inherited chromosome 11 (paternal uniparental disomy), then the chance of having a child with Beckwith-Wiedemann syndrome is likely very low.

If an individual has Beckwith-Wiedemann syndrome due to an imprinting error caused by a small deletion or duplication of chromosome 11p15.5, then the chance to pass on that deletion or duplication would be 50%. Each person needs a normal maternal and paternal copy of this chromosome region. When the maternal copy is abnormal, it leads to Beckwith-Wiedemann syndrome. However, when the paternal copy is abnormal, it leads to a different condition known as Russell-Silver syndrome. Therefore, if a woman has Beckwith-Wiedemann syndrome due to an imprinting error caused by a small deletion or duplication of chromosome 11p15.5, each of her offspring have a 50% risk to have Beckwith-Wiedemann syndrome as well. If a man has Beckwith-Wiedemann syndrome due to an imprinting error caused by a small deletion or duplication of chromosome 11p15.5, each of his offspring have a 50% risk to have Russell-Silver syndrome. To read more about Russell-Silver syndrome, review a reliable resource such as the Genetics Home Reference review on Russell-Silver syndrome.

When neither the woman nor man in a couple has Beckwith-Wiedemann syndrome but the couple has had one child with Beckwith-Wiedemann syndrome, the chance for them to have another affected child depends on three factors:

The inheritance of Beckwith-Wiedemann syndrome is complicated due to the fact that there are several ways in which genetic changes can cause this condition. Each of these different genetic changes carries different risks for other family members to inherit Beckwith-Wiedemann syndrome.

About 85% of people with Beckwith-Wiedemann syndrome are the only one in their family with the condition. About 10-15% of people with Beckwith-Wiedemann syndrome inherited the condition from a parent who may or may not be affected themselves. When inherited, Beckwith-Wiedemann follows an autosomal dominant pattern, meaning only one copy of the gene change is needed to cause the condition. In inherited cases, the condition is more likely to be passed if the mother is the one who carries the gene change.

Rarely, in less than 1% of cases, Beckwith-Wiedemann syndrome is caused by a change in the structure of chromosome 11. In some cases, these chromosome changes are inherited from a parent and in others they occur spontaneously.

Speaking with a genetic counselor can help families who have questions about how Beckwith-Wiedemann syndrome is inherited and who in the family is also at risk for the condition. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

There are a few different ways to donate money to help with research on Beckwith-Wiedemann syndrome. Donations are accepted by the Beckwith-Wiedemann Syndrome Fund at Alex’s Lemonade Stand Foundation to further the research on Beckwith-Wiedemann syndrome.

Alternatively, The National Organization for Rare Disorders (NORD) is a patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them, including Beckwith-Wiedemann syndrome. Donations to NORD can be made here.

It is believed that about 1 in every 13,700 babies will be born with Beckwith-Wiedemann syndrome. However, it may be more common as some people are not as severely affected and may not be diagnosed.

Children who have symptoms suspicious for Beckwith-Wiedemann syndrome will generally have a karyotype performed. A karyotype is a photographic view of the chromosomes within a cell to look for missing or extra copies of one ore more chromosomes, missing or extra pieces of any of the chromosomes, and any abnormal layout or structure of one or more chromosomes. Often at the same time, methylation studies of the imprinting regions on chromosome 11 will be looked at. In cases in which other family members also have the condition, the CDKN1C gene may be looked at specifically to look for changes. In families in which there are multiple people with Beckwith-Wiedemann syndrome but a change in the CDKN1C gene was not found and the karyotype was normal, testing may be done to look for small areas of DNA that were duplicated or deleted. These tests are all typically done on a sample of blood taken from the arm.

People with Beckwith-Wiedemann syndrome may have kidney problems that lead to low blood sugar (hypoglycemia). If untreated, low blood sugar can cause problems with the central nervous system. Additionally, urinary tract infections should be treated as soon as they occur to avoid kidney damage.

The severity of the overgrowth can vary between different people with Beckwith-Wiedemann syndrome. Some people who have milder forms of the condition may not even be aware that they have Beckwith-Wiedemann syndrome.

Some, but not all, cases of Beckwith-Wiedemann syndrome can be suspected prenatally. If there is a known family history of Beckwith-Wiedemann syndrome and the pregnancy is at risk based on that history, the diagnosis may be suspected. About half of pregnancies involving a baby with Beckwith-Wiedemann syndrome may have too much amniotic fluid (polyhydramnios) and/or may have the entire body or parts of the body being larger than expected (macrosomia). A birth defect known as an omphalocele, where some of the abdominal organs spill into the belly button region, is often diagnosed prenatally. Although omphalocele can be seen in babies with chromosome disorders and genetic disorders other than Beckwith-Wiedemann syndrome, as well as as an isolated defect in a baby without an underlying genetic syndrome, Beckwith-Wiedemann syndrome should be considered as part of the differential diagnosis of a baby with an omphalocele. Other signs of the condition prenatally may include a long umbilical cord and a placenta that is almost twice as large as would be expected.

There do not appear to be psychiatric conditions associated with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome is known by several other names including:

Treatment for Beckwith-Wiedemann syndrome includes treating the individual symptoms of the condition. Low blood sugar (hypoglycemia) should be treated to prevent problems with the central nervous system. An opening of the abdominal wall (omphalocele) is often repaired surgically. Different feeding options may be recommended if the abnormally large tongue (macroglossia) causes problems feeding. Additionally, babies or young children with macroglossia may have a surgery to reduce the size of the tongue in addition to attending speech therapy. Surgery to correct uneven growth may be corrected during puberty. Tumors, whether cancerous or noncancerous, are treated by the same methods as they would in other children.

Beckwith-Wiedemann syndrome usually causes larger than average size and weight at birth, increased growth after birth, a large tongue (macroglossia), certain internal organs being larger than normal (visceromegaly), and protrusion of some of the intestines and organs through a hole in the wall of the stomach or belly button (omphalocele or umbilical hernia).

Learning problems have not been associated with Beckwith-Wiedemann syndrome. The majority of people with Beckwith-Wiedemann syndrome have normal intelligence. Exactly how smart a person with Beckwith-Wiedemann syndrome is will vary as it does for people without Beckwith-Wiedemann syndrome.

There are many support groups for Beckwith-Widemann syndrome:

Beckwith-Wiedemann syndrome is a condition that is present at birth, but the overgrowth (macrosomia) and large tongue (macroglossia) often associated with this condition may present until some time after birth.

Some individuals with Beckwith-Wiedemann syndrome have a form due to something known as "segmental mosaicism." Mosaicism in Beckwith-Wiedemann syndrome occurs when the genetic change that causes the disorder happens after fertilization in one cell of a developing embryo. Those cells that carry the genetic change divide and go on to make up parts of different tissues in the body, but the abnormal gene is not present in all of the cells. The cells without the gene change go on to develop normally, whereas those that carry the gene change do not. Individuals with segmental mosaicism for Beckwith-Wiedemann can have specific parts of their body on one side of the body or the other that will grow abnormally large making them look uneven. This uneven growth (hemihyperplasia) usually becomes less obvious as the child gets older.

There are some physical features common to Beckwith-Wiedemann syndrome. However, it is important to realize that not everyone with Beckwith-Wiedemann has all of these features and that every person with this condition is different from one another. Children with the condition may be taller than their classmates during childhood. Some babies with Beckwith-Wiedemann syndrome are born with an opening in their abdominal wall causing their organs to spill through the belly-button (omphalocele) or an out-pouching near their belly-button (umbilical hernia). Others with this condition may have a large tongue (macroglossia), larger than normal abdominal organs (visceromegaly), and/or creases or pits in the skin near the ears.

The following conditions have symptoms which overlap with Beckwith-Wiedemann syndrome and should be considered when trying to diagnose someone with Beckwith-Wiedemann syndrome:

As of June 2016, there are no hospitals or clinics which are specifically designated as a "Center of Excellence" in Beckwith-Wiedemann syndrome. Nonetheless, there are some doctors and researchers that specialize in Beckwith-Wiedemann syndrome. Ideally, individuals with Beckwith-Wiedemann syndrome should be followed by a medical geneticist. Medical geneticists are physicians who specialize in diagnosing and managing genetic disorders. A medical geneticist will be familiar with Beckwith-Wiedemann syndrome and will be able to answer families’ questions and take proper care of the affected individual. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website .