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Last updated: 8/8/2023
Years published: 1985, 1988, 1989, 1990, 1993, 1994, 1997, 1999, 2000, 2002, 2007, 2016, 2019, 2023
NORD gratefully acknowledges Jennifer Kalish, MD, PhD, Attending Physician, Division of Human Genetics, Mallory Byrne, APRN, CPNP-AC, CPN, Evan R. Hathaway LCGC and Laura Voss, LCGC, Childrenโs Hospital of Philadelphia, for the preparation of this report.
Beckwith-Wiedemann syndrome (BWS) is the most common overgrowth and cancer predisposition disorder. BWS is caused by changes on chromosome 11p15.5 and is characterized by a wide spectrum of symptoms and physical findings that vary in range and severity from person to person. Associated features include a large tongue (macroglossia), abdominal wall abnormalities (omphalocele, umbilical hernia or diastasis recti), abnormal enlargement of one side or structure of the body (lateralized overgrowth) resulting in unequal (asymmetric) growth, an increased risk of developing certain childhood cancers, most commonly Wilms tumor (kidney tumor) and hepatoblastoma (liver tumor) and low blood sugar levels in the first few days of life (neonatal hypoglycemia) or beyond leading to persistent low blood sugars (hyperinsulinism). BWS may also be associated with above-average birth weight (large for gestational age), increased growth after birth (macrosomia), enlargement of certain internal organs (organomegaly), distinctive grooves in the ear lobes (ear creases and ear pits), and a characteristic facial appearance.
Beckwith-Wiedemann syndrome has been recently reclassified as Beckwith-Wiedemann spectrum as the clinical presentation can vary from patient to patient. Approximately 80% of people with BWS have chromosome changes that appear to occur randomly (sporadically). Familial transmission (inherited forms) occurs in about 5-10% of patients with BWS. About 14% of patients with BWS have an unknown cause for diagnosis. BWS affects at least one in 10,340 live births. Researchers have determined that BWS results from various abnormalities affecting the normal, proper expression of certain genes that control growth within a specific region of chromosome 11 (BWS critical region).
The characteristic features of BWS vary greatly from person to person, which can make clinical diagnosis based on physical exam findings and molecular diagnosis based on genetic testing challenging. Sometimes, the clinical and molecular diagnoses do not match because clinically the patients may not have many obvious physical features of BWS even if they have changes in the BWS critical region based on genetic testing. Some individuals may appear mildly affected while others appear more significantly affected. Affected individuals may not have all the symptoms listed. The range of clinical features due to changes on chromosome 11p15.5 has been redefined as the Beckwith-Wiedemann spectrum.
Some infants with BWS are born prematurely, but still have an excessive birth weight (large for gestational age). Over half of infants with BWS are above the 97th percentile in weight for gestational age. Overgrowth can continue throughout childhood (macrosomia). Abnormal enlargement of one side or structure of the body (lateralized overgrowth) may occur, resulting in asymmetric growth. Lateralized overgrowth or isolated lateralized overgrowth (ILO) is a new term used to describe what was previously called hemihypertrophy or hemihyperplasia. ILO is defined as asymmetric overgrowth of the body. ILO is not limited to one side of the body, and it does not specify what part or tissue is displaying overgrowth. For example, a patient may have a larger left arm and a larger right leg.
Abdominal wall abnormalities can include an omphalocele (also known as exomphalos), in which part of an infantโs intestines and other abdominal organs are outside of the body because of an opening in the belly button. The intestines and other organs are covered by a thin membrane. Less severe abdominal abnormalities can include protrusion of part of the intestines through an abnormal opening in the muscular wall of the abdomen near the umbilical cord (umbilical hernia), or weakness and separation of the left and right muscles of the abdominal wall (diastasis recti). Additionally, the internal organs of affected individuals can become abnormally enlarged (organomegaly). Any or all of the following organs may be affected: liver, spleen, pancreas, kidneys or adrenal glands.
Some newborns with BWS may have low blood sugar (neonatal hypoglycemia or hyperinsulinism) due to overgrowth and excessive secretion of the hormone insulin by the pancreas. Insulin helps regulate blood glucose levels by promoting the movement of glucose into cells. Most infants with neonatal hypoglycemia associated with BWS have mild and transient symptoms that resolve without treatment. However, without proper detection and appropriate treatment, neurological complications may result. Congenital hyperinsulinism is the most common cause for persistent and severe low blood sugar.
Patients with BWS may have an enlarged tongue (macroglossia), which can cause difficulties in speaking, feeding and breathing. In addition to macroglossia, BWS may be characterized by other differences of the skull and facial (craniofacial) region. Such features may include distinctive slit-like grooves or creases in the ear lobes and dimples on the back of the ears (ear creases or pits). Some infants may have flat, pale red or reddish-purple facial marks at birth, most commonly on the eyelids and forehead, which consist of abnormal clusters of small blood vessels (facial nevus simplex). Such marks typically become less apparent during the first year of life. In patients with lateralized overgrowth, one side of the face may appear larger than the other. Some patients may have improper contact of the teeth of the upper and lower jaws (malocclusion) and abnormal protrusion of the lower jaw (mandibular prognathism), features that may occur secondary to macroglossia.
A variety of kidney (renal) abnormalities can occur in individuals with BWS, including abnormally large kidneys (nephromegaly), improper development of the innermost tissues of the kidney (renal medullary dysplasia) and the formation of calcium deposits in the kidney (nephrocalcinosis), which could potentially impair kidney function. Additional abnormalities include duplication of the series of tubes and ducts through which the kidneys reabsorb water and sodium (duplicated collecting system), widening of some of the small tubes and collecting ducts (medullary sponge kidney) and the presence of small pouches (diverticula) on the kidneys. Kidney stones have been reported to occur in adolescents and adults with BWS.
Patients with BWS may have an increased risk of developing certain childhood cancers. Embryonal cancers occur in approximately 8% of patients with BWS. The most common types of tumors are Wilms tumor (a kidney tumor) and hepatoblastoma (a liver tumor). Neuroblastoma (a nerve cell tumor), rhabdomyosarcoma (a soft tissue tumor) and adrenal carcinoma (an adrenal gland tumor) have been reported more rarely. The overall tumor risk is highest during the first two years of life.
Many clinical features of BWS become less evident with increasing age and many adults experience normal growth and appearance. Neurological (brain) development appears to be unaffected in BWS, unless associated with prolonged, untreated neonatal hypoglycemia, extreme prematurity, or a chromosomal duplication. Adult patients may present with medical issues related to these clinical features, and some have required surgery in early childhood. Most features in adults with BWS, such as renal issues and back pain, are consequences of pediatric issues. However, more research is needed to determine the relationship between features of adults with BWS and pediatric symptoms.
Genetics is the study of genes whereas epigenetics is the study of how those genes are turned on or off (gene expression). BWS results from various abnormalities affecting the proper expression of genes that control growth within a specific region of chromosome 11(11p15.5). This region is referred to as the BWS critical region.
Approximately 80% of people with BWS have no family history of this syndrome. For these people, BWS is usually caused by epigenetic changes that appear to occur randomly (sporadically). More rarely, BWS is caused by genetic changes that are passed down from a parent (inherited). Approximately 5-10% of patients have BWS due to a family history of the syndrome. About 14% of patients with BWS have an unknown cause for diagnosis.
Everyone has two copies of every gene, one received from the father, and one received from the mother. In most people, both genes are โturned onโ or active. However, some genes are โturned offโ or preferentially silenced based upon which parent that gene came from (a process known as genomic imprinting). Genomic imprinting is controlled by marks on the DNA called methylation. Proper genomic imprinting is necessary for normal development and defective imprinting on chromosome 11 can lead to BWS. Several genes that control growth on chromosome 11 are imprinted, which means that the gene is only active from the motherโs chromosome or the fatherโs chromosome but not both.
Imprinted genes tend to be clustered or grouped together. Chromosome 11p15.5 has two imprinting cluster regions known as imprinting centers 1 and 2 (IC1 and IC2). Several specific imprinted genes are located in these regions. The improper imprinting of these two regions leads to the improper expression of the genes located within the regions, playing a role in the development of BWS. These genes include H19 (a gene that signals not to grow), IGF2 (insulin-like growth factor II), KCNQ10T1 (LIT1) and CDKN1C (p57[KIP2]) (a gene that signals not to grow).
H19 is a long noncoding RNA thought to play a role in inhibiting growth. IGF2 is a growth factor. KCNQ10T1 is a noncoding RNA and CDKN1C is a cell cycle regulator and tumor suppressor. Researchers believe that the paternally expressed genes promote growth and that the maternally expressed genes act as tumor suppressor genes or inhibit growth. Normally, H19 and CDKN1C are expressed from the maternal chromosome and IGF2 and KCNQ1OT1 are expressed from the paternal chromosome. Improper methylation in the BWS critical region can lead to an imbalance of the โgrowโ and โdonโt growโ signals, leading to overgrowth.
Gain of methylation (hypermethylation) at imprinting center 1 (IC1 GOM) occurs in about 5% of patients with BWS. This leads to decreased H19 expression and increased IGF2 expression.
Imprinting center 2 (IC2) is associated with KvDMR, a chemical switch found on the KCNQ1 gene. Loss of methylation (hypomethylation) at KvDMR of imprinting center 2 (IC2 LOM) occurs in about 50% of people with BWS. This leads to increased KCNQ10T1 (long QT intronic transcript 1 [LIT1]) expression and decreased CDKN1C expression.
Imprinting errors may also be caused by a chromosomal abnormality known as uniparental disomy (UPD). UPD occurs when a person receives both copies of a chromosome (or part of a chromosome) from one parent instead of receiving one copy from each parent. Approximately 20% of people with BWS have UPD. In BWS, both copies of chromosome 11 are received from the father (paternal uniparental disomy (pUPD)). As a result, there are too many active paternally expressed genes (IGF2) in this region and not enough maternally expressed genes (H19, CDKN1C). Uniparental paternal disomy occurs after fertilization, and therefore the risk of recurrence is extremely low.
Mosaic genome-wide paternal uniparental isodisomy (GWpUPD) occurs in about 10% of BWS due to pUPD (approximately 2% of all patients with BWS). In the case of GWpUPD, every chromosome is inherited from the father in the cells that carries the abnormality, instead of just chromosome 11 as in pUPD. GWpUPD is associated with a greater tumor risk. The severity of GWpUPD varies according to the number of cells affected and where the affected cells are located within the patient.
Changes (variants or mutations) of the CDKN1C gene have been detected in some individuals with BWS. The loss of proper expression or โunderexpressionโ of the gene is thought to play an important role in causing the disorder. Approximately 5% of people with BWS are found to have variants of the CDKN1C gene. The variant is inherited in an autosomal dominant pattern, which means that only one copy of the changed gene is needed for the disorder to occur. However, CDKN1C is normally only maternally expressed, and therefore, children will only be affected (i.e., have BWS) if the variant is passed from the mother. Approximately 40% of individuals with a family history of BWS have variants of the CDKN1C gene. Variants in CDKN1C can also occur randomly without the mother carrying the variant (de novo). Patients with BWS due to CDKN1C changes have a 50% risk of passing the variant to their children.
Research has shown that small deletions (microdeletions) affecting imprinting center 1 (IC1) of chromosome 11p15.5 may be the cause of familial BWS in some people. Approximately 1-2% of patients with BWS have deletions involving 11p15.5. Microdeletions of the KCNQ10T1 (LIT1) gene have also been identified in some people with BWS. These microdeletions appear to cause BWS when inherited maternally; when inherited paternally, the disorder does not develop. Small duplications (microduplications), affecting imprinting center 1 (IC1) of chromosome 11p15.5 inherited from the father can also cause BWS. These microduplications can also occur randomly (de novo).
Approximately 2-4% of cases of BWS are due to various chromosomal abnormalities involving the 11p15.5 chromosomal region. This includes chromosomal inversions or rearrangements (translocations) or the presence of extra chromosomal material (duplications).
Phenotype genotype correlation
Researchers are investigating if specific causes of BWS are associated with specific symptoms (genotype-phenotype correlation). Research indicates that omphalocele and macroglossia are more common in individuals with defects of IC2 or a variant in the CDKN1C gene. Patients with pUPD are at a greater risk for lateralized overgrowth and hyperinsulinism. Individuals with defects of IC1 or pUPD appear to be at a greater risk of developing an associated tumor such as Wilms tumor. Patients with pUPD also have a greater risk of developing a liver tumor (hepatoblastoma). The different molecular types of BWS each carry a different tumor risk. More research is necessary to determine how the specific causes of BWS correlate with the various symptoms of the disorder.
BWS affects males and females in equal numbers. It is estimated to occur in 1 in 10,340 individuals in the general population. Because people who are mildly affected may go undiagnosed, it is difficult to determine the true frequency of BWS in the general population.
There is no specific increased risk for BWS within specific race/ethnicity populations, although the clinical presentations may vary between groups.
Research suggests that patients conceived with assistive reproductive technology (ART) such as in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) may be at a greater risk of developing disorders resulting from genomic imprinting (such as BWS) than the general population. A recent study revealed a tenfold increased risk for BWS in patients conceived via ART, with a prevalence of one in 1,126 patients. Most patients with BWS who are conceived through ART have BWS due to IC2 LOM. More research is necessary to determine the exact relationship between such technologies and the development of BWS.
Studies have also shown that the frequency of twin pregnancies is more common in the BWS population than in the general population. However, twins with BWS tend to present with varying levels of severity making it challenging for physicians to diagnose twins with BWS.
Patients with BWS can be diagnosed both before and after birth (prenatally and postnatally) either by physical evaluation (clinical diagnosis) and/or genetic testing (molecular diagnosis).
In some cases, certain procedures may be performed before birth (prenatally) to detect BWS. For example, ultrasound imaging may allow assessment of organ size and overall size of the developing fetus and potentially reveal other findings that may be suggestive of BWS. Features that can be detected by prenatal imaging include increased amniotic fluid surrounding the fetus (polyhydramnios), an enlarged placenta, omphalocele, enlarged abdominal circumference, nephromegaly, macroglossia and/or other abnormalities. The most common prenatally detected feature that leads to a higher clinical suspicion of BWS is an omphalocele. If BWS is suspected, prenatal testing is available.
BWS may be diagnosed or confirmed shortly after birth based on a thorough clinical evaluation, detection of characteristic physical findings (e.g., increased weight and length, macroglossia, abdominal wall defects) and genetic testing of the BWS critical region.
BWS spectrum can be further divided into three subcategories: classic or typical BWS, atypical BWS and isolated lateralized overgrowth. A patient who presents with physical features and who appears more affected is thought to present with classic or typical BWS. A patient with fewer isolated features, such as neonatal hyperinsulinism or an embryonal tumor, is thought to present with โatypicalโ BWS. Finally, some patients may present with only isolated lateralized overgrowth.
A BWS consensus scoring system has been established to help with the clinical diagnosis of BWS and to determine the need for molecular testing. Features that will more likely lead to a diagnosis of BWS are termed โcardinal featuresโ (including macroglossia, omphalocele, lateralized overgrowth, multiple Wilms tumors, hyperinsulinism and specific pathology findings including adrenal cytomegaly (enlargement of the cells in the adrenal gland) and placental mesenchymal dysplasia (enlargement of cells in the placenta). As such, cardinal features are given two points each in the scoring system. Features that are seen in BWS but are also present in the general population are termed โsuggestive featuresโ (including large birth weight, macrosomia, facial nevus simplex, polyhydramnios or large placenta, ear creases or pits, hypoglycemia, embryonal tumors such as single Wilms tumors or hepatoblastomas, nephromegaly or hepatomegaly, umbilical hernia and diastasis recti). Suggestive features are given one point each. A total of four or more points, two of which should be due to a cardinal feature, is consistent with a clinical diagnosis of BWS. A total of two or more points indicates the need for molecular testing, especially if a cardinal feature is present.
Genetic testing looks for changes in the BWS critical region. This includes looking at the methylation marks (11p15.5 methylation analysis) on the DNA followed by looking at the number of copies of the imprinting control regions (11p15.5 copy number analysis) that are present in that region (normally there should be two copies). This will detect if there are deletions or duplications of the region. Additionally, if previous testing is normal, CDKN1C sequencing is performed to detect any changes in the CDKN1C gene. Additional testing that looks at all the chromosomes is recommended for patients determined to have UPD based on the methylation analysis. A chromosome microarray or a single nucleotide polymorphism (SNP) array is used to detect the extent of the region of UPD.
Not every patient with a clinical diagnosis of BWS will have a diagnosis that is confirmed by molecular testing. This is because most of the genetic and epigenetic changes that cause BWS are not present in every cell. This is termed โmosaicism.โ For this reason, testing multiple tissues can increase the likelihood of finding the cause of BWS. Negative testing on blood, for example, may not necessarily exclude a diagnosis. A recent study demonstrated that testing multiple tissues increased the likelihood of a molecular diagnosis from 70% to 82%.
Treatment
The treatment of BWS is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Geneticists, pediatricians, plastic surgeons, endocrinologists, nephrologists (kidney specialists), orthodontists (dental specialists), pulmonologists (lung specialists), speech pathologists, pediatric oncologists and other healthcare professionals may need to plan an affected childโs treatment systematically and comprehensively.
In newborns with BWS, regular monitoring of blood glucose levels should be performed to ensure prompt detection and treatment of hypoglycemia in the immediate neonatal period. Although neonatal hypoglycemia is usually mild and temporary, its early detection and treatment is essential in preventing associated neurologic complications. Treatment measures may include the administration of intravenous glucose, frequent feedings, certain medications (e.g., diazoxide or octreotide) and/or surgical intervention in some cases.
In many infants with umbilical hernia, the defect may spontaneously disappear by the age of approximately one year. Surgery is usually not required unless an umbilical hernia becomes progressively larger, does not spontaneously resolve (e.g., by about three or four years of age) and/or is associated with certain complications. However, in newborns with an omphalocele, surgical repair of the defect is typically required shortly after birth.
Like other features associated with BWS, macroglossia can vary in severity. Patients with macroglossia are at an increased risk for obstructive sleep apnea, feeding difficulties, speech difficulties and potential jaw development issues. Patients with macroglossia require the support of a multidisciplinary team. They should undergo feeding evaluation and sleep studies in addition to consultations with plastic surgeons and pulmonologists if needed. Feeding difficulties caused by macroglossia may require the support of feeding specialists or dieticians. Treatment may include the use of specialized nipples or the temporary insertion of a nasogastric tube. Speech difficulties may require the support of speech therapy. A pulmonologist can evaluate the degree to which macroglossia affects a patientโs breathing and sleeping. A sleep study may be used to assess obstructive sleep apnea, airway obstruction, airway resistance, severe desaturation, sleep disordered breathing and snoring. Continuous positive airway pressure (CPAP) is a method used to support children with obstructive sleep apnea. Some patients may undergo tongue reduction surgery with the goal of improving breathing, feeding and jaw or dental malformations due to macroglossia. Patients with macroglossia should be followed closely by a multidisciplinary team.
Regular orthopedic evaluation is recommended for patients with lateralized overgrowth and an associated leg length difference. Some patients with significant lateralized overgrowth of the limbs may require shoe lifts and, in other patients, surgical correction may be needed.
Infants and patients with BWS should undergo regular abdominal and renal ultrasounds, and measurement of serum alpha-fetoprotein levels as recommended to ensure early detection and treatment of certain malignancies that may occur in association with BWS (e.g., Wilms tumor, hepatoblastoma).
Alpha-fetoprotein (AFP) is a protein produced by the liver. AFP levels typically decline during infancy; however, AFP may be abnormally elevated in blood if certain tumors are present (hepatoblastoma). The trend in AFP levels over time should be followed in patients with BWS and normal AFP values for children with BWS are available to aid in interpretation of results. There have been recent discussions regarding the utility of AFP screening in young children. While some suggest that the invasiveness of a regular blood draw may be stressful for many families, AFP has proven to be a useful early indicator for hepatoblastoma.
According to the United States-based guidelines, screening is recommended for all patients with a clinical or molecular diagnosis of BWS by AFP analysis and a full abdominal ultrasound every three months until the 4th birthday (to screen for hepatoblastoma and Wilms tumor) followed by renal ultrasounds every 3 months until 7th birthday (to screen for Wilms tumor). Additional screening by urine analysis and chest x-rays for neuroblastoma is recommended for patients with CDKN1C variants. Also, screening for patients with BWS due to GWpUPD may extend beyond the 7th birthday.
If a tumor develops in association with BWS, the appropriate treatment measures vary depending on the specific tumor present, the stage and/or extent of disease and/or other factors. Treatment methods may include surgery (for example, nephron-sparing kidney resection in the case of a Wilms tumor), use of certain anticancer drugs (chemotherapy), radiation therapy and/or other measures. (For more information on Wilms tumor, choose โWilmsโ as your search term in the Rare Disease Database.)
Patients with cardiac, gastrointestinal and renal abnormalities may require certain medications, surgery or other medical interventions. These patients should be referred to appropriate specialists.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Late-onset complications with BWS may require continued follow-up in adulthood. More research is needed to understand the features and associated treatments for adults with BWS.
A Beckwith-Wiedemann Registry was established to coordinate research efforts into Beckwith-Wiedemann syndrome. For more information on the Registry, contact:
Jennifer M. Kalish, MD, PhD
Attending Physician
Division of Human Genetics
The Childrenโs Hospital of Philadelphia
3501 Civic Center Boulevard
Colket Translational Research Building, Rm 3028
Philadelphia, PA 19104
Phone: 267-425-2467
Fax: 267-425-0007
E-mail: [email protected]
Website: https://www.research.chop.edu/bws-registry
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/
For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
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Vuillaume ML, et al. CUGC for Simpson-Golabi-Behmel syndrome (SGBS). European Journal of Human Genetics 2019; 27(4):663-668.
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Mussa A, et al. Assisted reproduction techniques and prenatal diagnosis of BeckwithโWiedemann spectrum presenting with omphalocele. Journal of Assisted Reproduction and Genetics 2018; 35(10): 1925-1926.
Kalish JM, et al. Nomenclature and definition in asymmetric regional body overgrowth. American Journal of Medical Genetics. 2017 Jul;173(7):1735-1738.
Mussa A, et al. Assisted Reproductive Techniques and Risk of Beckwith-Wiedemann Syndrome. Pediatrics 2017; 140(1).
Mussa A. and Ferrero GB. Serum alpha-fetoprotein screening for hepatoblastoma in Beckwith-Wiedemann syndrome. Am J Med Genet A. 2017; 173(3):585-587.
Mussa A, et al. Recommendations of the scientific committee of the Italian Beckwith-Wiedemann Syndrome Association on the diagnosis, management and follow-up of the syndrome. European Journal of Medical Genetics. 2016:59(1):52-64.
Edmondson A and Kalish JM. Overgrowth Syndromes J Ped Genet. 2015; 4(3): 135-143.
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Kalish JM, Jiang CL, Bartolomei MS. Epigenetics and Imprinting in Human Disease. Int J Dev Biol, 2014; 58: 291โ298.
Kalish JM, et al. Bilateral pheochromocytomas, hemihyperplasia, and subtle somatic mosaicism: the importance of detecting low-level uniparental disomy. Am J Med Genet A. 2013;161A(5): p. 993-1001.
Kalish JM, et al. Clinical features of three girls with mosaic genome-wide paternal uniparental isodisomy. Am J Med Genet A. 2013; 161A(8): 1929-39.
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INTERNET
Beckwith-Wiedemann Syndrome. The Childrenโs Hospital of Philadelphia. July 1, 2022. Available at: https://www.chop.edu/conditions-diseases/beckwith-wiedemann-syndrome Accessed August 8, 2023.
Beckwith-Wiedemann Syndrome. Genetics Home Reference. Dec 3, 2021. Available at: https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome Accessed August 8, 2023.
Shuman C, Kalish JM, Weksberg R. Beckwith-Wiedemann Syndrome. 2000 Mar 3 [Updated 2023 Jun 8]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1394/ Accessed August 8, 2023.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:130650; Last Update 01/19/2023. Available at: https://www.omim.org/entry/130650 Accessed August 8, 2023.
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Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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