National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Beckwith-Wiedemann syndrome

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Other Names:
Wiedemann-Beckwith Syndrome (WBS); Exomphalos macroglossia gigantism syndrome; EMG Syndrome
Categories:
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.[1][2][3] Some people only have one symptom while others may have many of the symptoms.[2] 

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.[1][2]

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.[2] Recommended management of BWS includes screening for the development of Wilms tumor, rhabdomyosarcoma, and hepatoblastoma.[3]
Last updated: 11/29/2017
The symptoms of Beckwith-Wiedemann syndrome (BWS) vary from person to person. Some people with BWS have many of the symptoms, and some have very few.  Most people with BWS have one or more of the following features or symptoms:[4][5]
  • 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
Last updated: 3/10/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Large for gestational age
Birth weight > 90th percentile
Birthweight > 90th percentile
[ more ] 		0001520
Tall stature
Increased body height
0000098
30%-79% of people have these symptoms
Abnormality of the shape of the midface 0430026
Accelerated skeletal maturation
Advanced bone age
Early bone maturation
[ more ] 		0005616
Anterior creases of earlobe
Earlobe crease
0009908
Branchial cyst 0009796
Choroideremia 0001139
Coarse facial features
Coarse facial appearance
0000280
Congenital diaphragmatic hernia 0000776
Enlarged kidney
Large kidneys
0000105
Exocrine pancreatic insufficiency
Inability to properly digest food due to lack of pancreatic digestive enzymes
0001738
Hemihypertrophy
Asymmetric overgrowth
0001528
Hypercalciuria
Elevated urine calcium levels
0002150
Infra-orbital crease
Crease in skin under the eye
Groove in skin under the eye
[ more ] 		0100876
Large placenta 0006267
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ] 		0000158
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ] 		0000303
Melanocytic nevus
Beauty mark
0000995
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Neonatal hypoglycemia
Low blood sugar in newborn
0001998
Nephropathy 0000112
Nevus flammeus
port-wine stain
0001052
Obesity
Having too much body fat
0001513
Omphalocele 0001539
Polyhydramnios
High levels of amniotic fluid
0001561
Posterior helix pit
Indentation in back of outer ear
0008523
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ] 		0001622
Prominent occiput
Prominent back of the skull
Prominent posterior skull
[ more ] 		0000269
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes
[ more ] 		0000520
Redundant skin
Loose redundant skin
Redundant skin folds
Sagging, redundant skin
[ more ] 		0001582
Subchorionic septal cyst 0030720
Umbilical hernia 0001537
Wide mouth
Broad mouth
Large mouth
[ more ] 		0000154
5%-29% of people have these symptoms
Abnormal pancreas morphology
Abnormally shaped pancreas
0012090
Adrenocortical carcinoma 0006744
Adrenocortical cytomegaly 0008186
Cardiomegaly
Enlarged heart
Increased heart size
[ more ] 		0001640
Cleft palate
Cleft roof of mouth
0000175
Congenital megaureter 0008676
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Dandy-Walker malformation 0001305
Diastasis recti
Gap between large left and right abdominal muscles
0001540
Elevated alpha-fetoprotein 0006254
Facial hemangioma 0000329
Feeding difficulties in infancy 0008872
Gonadoblastoma 0000150
Hepatoblastoma 0002884
Hepatomegaly
Enlarged liver
0002240
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Hypothyroidism
Underactive thyroid
0000821
Inguinal hernia 0000023
Large intestinal polyposis 0030255
Leiomyosarcoma 0100243
Multiple renal cysts
Multiple kidney cysts
0005562
Nephroblastoma 0002667
Nephrolithiasis
Kidney stones
0000787
Neuroblastoma
Cancer of early nerve cells
0003006
Neurodevelopmental delay 0012758
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ] 		0002167
Otosclerosis 0000362
Polycythemia
Increased red blood cells
0001901
Prominent metopic ridge 0005487
Rhabdomyosarcoma 0002859
Sleep apnea
Pauses in breathing while sleeping
0010535
Splenomegaly
Increased spleen size
0001744
Ureteral duplication
Double ureter
0000073
Urogenital fistula 0100589
Vesicoureteral reflux 0000076
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
1%-4% of people have these symptoms
Arnold-Chiari malformation 0002308
Pseudohypoparathyroidism 0000852
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Cardiomyopathy
Disease of the heart muscle
0001638
Large fontanelles
Wide fontanelles
0000239
Nephrocalcinosis
Too much calcium deposited in kidneys
0000121
Overgrowth
General overgrowth
0001548
Overgrowth of external genitalia 0003247
Pancreatic hyperplasia 0006277
Renal cortical cysts 0000803
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Last updated: 7/1/2020
The causes of Beckwith-Wiedemann syndrome (BWS) are very complex. BWS usually results from abnormal gene regulation in a particular region of chromosome 11.[1] Gene regulation is the process of turning genes "on" or "off" and ensures that the appropriate genes are expressed at the proper times.[6]

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.[1]

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.[1][3]

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.[1]

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.[1]

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).[1][3]

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.[3]
Last updated: 11/29/2017
In about 85% percent of cases of Beckwith-Wiedemann syndrome (BWS), only one person in a family has been diagnosed. However, the parents of an affected child may be at risk of having other affected children; the risk depends on the underlying genetic cause in each case.[1][2]

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.[2] 

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.[1][2] 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.[1]

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.[2] 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.[3] 
Last updated: 11/29/2017

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Simpson-Golabi-Behmel, Costello, Perlman, and Sotos syndromes, and mucopolysaccharidosis type VI (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Beckwith-Wiedemann syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Beckwith-Wiedemann syndrome. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Beckwith-Wiedemann syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Beckwith-Wiedemann syndrome. Genetics Home Reference. June, 2015; http://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome.
  2. Shuman C, Beckwith JB, Smith AC & Weksberg R. Beckwith-Wiedemann Syndrome. GeneReviews. 2016; http://www.ncbi.nlm.nih.gov/books/NBK1394/.
  3. Kalish JM, Doros L & Helman LJ. Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma. American Association of Cancer Research. http://clincancerres.aacrjournals.org/content/clincanres/23/13/e115.full.pdf.
  4. Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J et al.. Expert Consensus Document: Clinical and Molecular Diagnosis, Screening and Management of Beckwith-Wiedemann Syndrome: An International Consensus Statement. Nat Rev Endocrinol. Apr 2018; 14(4):229-249. https://www.ncbi.nlm.nih.gov/pubmed/29377879.
  5. Wang KH, Kupa J, Duffy KA, Kalish JM. Diagnosis and Management of Beckwith-Wiedemann Syndrome.. Front Pediatr. Jan 21, 2020; 7(562):1-12. https://www.ncbi.nlm.nih.gov/pubmed/32039119.
  6. Gene regulation. Genetics Home Reference. August 18, 2015; http://ghr.nlm.nih.gov/glossary=generegulation.