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Disease Profile

Beckwith-Wiedemann syndrome

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-5 / 10 000

US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Wiedemann-Beckwith Syndrome (WBS); Exomphalos macroglossia gigantism syndrome; EMG Syndrome


Congenital and Genetic Diseases


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 CDKN1CH19IGF2, 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]


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

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.


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]


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.
      Medical Terms Other Names
      Learn More:
      HPO ID
      80%-99% of people have these symptoms
      Large for gestational age
      Birth weight > 90th percentile
      Birthweight > 90th percentile

      [ more ]

      Tall stature
      Increased body height
      30%-79% of people have these symptoms
      Abnormality of the shape of the midface
      Accelerated skeletal maturation
      Advanced bone age
      Early bone maturation

      [ more ]

      Anterior creases of earlobe
      Earlobe crease
      Coarse facial features
      Coarse facial appearance
      Congenital diaphragmatic hernia
      Enlarged kidney
      Large kidneys
      Exocrine pancreatic insufficiency
      Inability to properly digest food due to lack of pancreatic digestive enzymes
      Asymmetric overgrowth
      Elevated urine calcium levels
      Infra-orbital crease
      Crease in skin under the eye
      Groove in skin under the eye

      [ more ]

      Large placenta
      Abnormally large tongue
      Increased size of tongue
      Large tongue

      [ more ]

      Mandibular prognathia
      Big lower jaw
      Increased projection of lower jaw
      Increased size of lower jaw
      Large lower jaw
      Prominent chin
      Prominent lower jaw

      [ more ]

      Melanocytic nevus
      Beauty mark
      Midface retrusion
      Decreased size of midface
      Midface deficiency
      Underdevelopment of midface

      [ more ]

      Neonatal hypoglycemia
      Low blood sugar in newborn
      Nevus flammeus
      port-wine stain
      Having too much body fat
      High levels of amniotic fluid
      Posterior helix pit
      Indentation in back of outer ear
      Premature birth
      Premature delivery of affected infants
      Preterm delivery

      [ more ]

      Prominent occiput
      Prominent back of the skull
      Prominent posterior skull

      [ more ]

      Bulging eye
      Eyeballs bulging out
      Prominent eyes
      Prominent globes
      Protruding eyes

      [ more ]

      Redundant skin
      Loose redundant skin
      Redundant skin folds
      Sagging, redundant skin

      [ more ]

      Subchorionic septal cyst
      Umbilical hernia
      Wide mouth
      Broad mouth
      Large mouth

      [ more ]

      5%-29% of people have these symptoms
      Abnormal pancreas morphology
      Abnormally shaped pancreas
      Adrenocortical carcinoma
      Adrenocortical cytomegaly
      Enlarged heart
      Increased heart size

      [ more ]

      Cleft palate
      Cleft roof of mouth
      Congenital megaureter
      Undescended testes
      Undescended testis

      [ more ]

      Dandy-Walker malformation
      Diastasis recti
      Gap between large left and right abdominal muscles
      Elevated alpha-fetoprotein
      Facial hemangioma
      Feeding difficulties in infancy
      Enlarged liver
      Hypertrophic cardiomyopathy
      Enlarged and thickened heart muscle
      Underactive thyroid
      Inguinal hernia
      Large intestinal polyposis
      Multiple renal cysts
      Multiple kidney cysts
      Kidney stones
      Cancer of early nerve cells
      Neurodevelopmental delay
      Neurological speech impairment
      Speech disorder
      Speech impairment
      Speech impediment

      [ more ]

      Increased red blood cells
      Prominent metopic ridge
      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.


      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

        Learn more

        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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Beckwith-Wiedemann syndrome. This website is maintained by the National Library of Medicine.
        • 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.


            1. Beckwith-Wiedemann syndrome. Genetics Home Reference. June, 2015; https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome.
            2. Shuman C, Beckwith JB, Smith AC & Weksberg R. Beckwith-Wiedemann Syndrome. GeneReviews. 2016; https://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. https://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; https://ghr.nlm.nih.gov/glossary=generegulation.

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