Beckwith-Wiedemann Syndrome (BWS)

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Disease Ontology 12 DOID:5572 OMIM 56 130650 KEGG 36 H00713 MeSH 43 D001506 NCIt 49 C34415 SNOMED-CT 67 81780002 ICD10 32 Q87.3

MESH via Orphanet 44 D001506 ICD10 via Orphanet 33 Q87.3 UMLS via Orphanet 72 C0004903 Orphanet 58 ORPHA116 ORPHA231120 ORPHA238613 MedGen 41 C0004903 SNOMED-CT via HPO 68 109504005 109843000 109992005 11543004 123982003 127062003 14447001 16294009 17190001 18265008 18735004 197811007 201093004 204878001 205838004 21119008 2227007 22810007 233873004 248328003 25081006 25273001 253184003 253883006 254211001 255035007 263681008 276709006 282020008 289263000 300444006 302847003 302849000 30924005 367494004 37992001 396232000 396347007 400096001 40159009 40930008 414915002 414916001 416377005 42362005 432328008 443719001 45024009 45227007 47367009 48638002 49496001 49550006 51549004 52767006 56007004 57809008 58976002 59857007 62629000 63567004 718485003 71938000 73430006 74751003 75241009 80515008 8186001 85898001 86203003 87364003 87979003 90708001 95576001 more UMLS 71 C0004903

NIH Rare Diseases : ⁵² Beckwith-Wiedemann syndrome (BWS) is a growth disorder that can affect several parts of the body. Babies and children are larger than normal usually until age 8, when growth slows down, resulting in an average height in adults. Symptoms may include one side or area of the body growing more than the other side (asymmetric growth or hemihyperplasia ), omphalocele or other abdominal wall defect at birth, low blood sugar (hypoglycemia) in infancy, an abnormally large tongue (macroglossia), abnormally large abdominal organs , creases or pits in the skin near the ears, and kidney abnormalities. Affected children have an increased risk to develop tumors , particularly a rare form of kidney cancer called Wilms tumor , a cancer of muscle tissue called rhabdomyosarcoma, and a form of liver cancer called hepatoblastoma . Some people only have one symptom while others may have many of the symptoms. The cause of BWS is complex and is different for different people, but involves genes that control body growth. The genes, including the CDKN1C , H19 , IGF2 , and KCNQ1OT1 genes, are located on chromosome 11. In most cases BWS is caused by problems with the genomic imprinting of these genes. Genomic imprinting refers to having some genes that are active (expressed) only when inherited from the father and others that are active only when inherited from the mother. Less commonly, changes or mutations in the CDKN1C gene or larger changes to chromosome 11, such as a translocation , deletion , or duplication , may cause BWS. Diagnosis of BWS is based on symptoms with the support of genetic testing . At present however, there is no clearly accepted diagnostic criteria as doctors are trying to understand the full spectrum of possible symptoms. While there is no cure for BWS, there are treatments available for many of the symptoms. Treatment may include medication for hypoglycemia, surgery to repair an omphalocele or other birth defect , or surgery to reduce size of the tongue (macroglossia repair). Early intervention, speech therapy, occupational therapy, and physical therapy may also be recommended. Evaluation by an orthopedic surgeon may be helpful depending on the areas of the body affected by overgrowth. Recommended management of BWS includes screening for the development of Wilms tumor, rhabdomyosarcoma, and hepatoblastoma.

MalaCards based summary : Beckwith-Wiedemann Syndrome, also known as wiedemann-beckwith syndrome, is related to beckwith-wiedemann syndrome due to imprinting defect of 11p15 and hemihyperplasia, isolated. An important gene associated with Beckwith-Wiedemann Syndrome is CDKN1C (Cyclin Dependent Kinase Inhibitor 1C), and among its related pathways/superpathways is Cell cycle. The drugs Acetylcholine and Dactinomycin have been mentioned in the context of this disorder. Affiliated tissues include Kidney, tongue and liver, and related phenotypes are tall stature and large for gestational age

Disease Ontology : ¹² A syndrome characterized by overgrowth (macrosomia), an increased risk of childhood cancer and congenital malformations.

Genetics Home Reference : ²⁵ Beckwith-Wiedemann syndrome is a condition that affects many parts of the body. It is classified as an overgrowth syndrome, which means that affected infants are considerably larger than normal (macrosomia) and tend to be taller than their peers during childhood. Growth begins to slow by about age 8, and adults with this condition are not unusually tall. In some children with Beckwith-Wiedemann syndrome, specific parts of the body on one side or the other may grow abnormally large, leading to an asymmetric or uneven appearance. This unusual growth pattern, which is known as hemihyperplasia, usually becomes less apparent over time. The signs and symptoms of Beckwith-Wiedemann syndrome vary among affected individuals. Some children with this condition are born with an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the belly-button. Other abdominal wall defects, such as a soft out-pouching around the belly-button (an umbilical hernia), are also common. Some infants with Beckwith-Wiedemann syndrome have an abnormally large tongue (macroglossia), which may interfere with breathing, swallowing, and speaking. Other major features of this condition include abnormally large abdominal organs (visceromegaly), creases or pits in the skin near the ears, low blood sugar (hypoglycemia) in infancy, and kidney abnormalities. Children with Beckwith-Wiedemann syndrome are at an increased risk of developing several types of cancerous and noncancerous tumors, particularly a form of kidney cancer called Wilms tumor and a form of liver cancer called hepatoblastoma. Tumors develop in about 10 percent of people with this condition and almost always appear in childhood. Most children and adults with Beckwith-Wiedemann syndrome do not have serious medical problems associated with the condition. Their life expectancy is usually normal.

OMIM : ⁵⁶ Beckwith-Wiedemann syndrome is a pediatric overgrowth disorder involving a predisposition to tumor development. The clinical presentation is highly variable; some cases lack the hallmark features of exomphalos, macroglossia, and gigantism as originally described by Beckwith (1969) and Wiedemann (1969) (summary by Weksberg et al., 2010). Mussa et al. (2016) provided a review of Beckwith-Wiedemann syndrome, including the wide spectrum of phenotypic manifestations, delineation of the frequencies of manifestations according to genotype, and discussion of the molecular and epigenetic defects that underlie the disorder. (130650)

KEGG : ³⁶ Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. It is associated with genetic or epigenetic abnormalities in a cluster of imprinted genes found within a genomic region of approximately one megabase on chromosome 11p15. The imprinted region 11p15 is separated into two domains, with each domain regulated by a functionally independent imprinting control regions (ICR). The centromeric ICR2 regulates the expression of CDKN1C, KCNQ1, and further genes. The majority of cases of BWS show hypomethylation in the ICR2 or mutations in the ICR2-regulated CDKN1C gene. In intron 10 of the KCNQ1 locus, the untranslated KCNQ1OT1 RNA is encoded. KCNQ10T1 is expressed by the paternal allele and probably represses realization of the CDKN1C gene. In the telomeric ICR1, hypermethylation of the H19 promoter and loss of imprinting of IGF2 have been reported in a small fraction of patients with BWS. A few BWS cases could be related to NSD1 deletions or mutations.

UniProtKB/Swiss-Prot : ⁷³ Beckwith-Wiedemann syndrome: A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors.

Wikipedia : ⁷⁴ Beckwith-Wiedemann syndrome (/'b?k?w?? 'vi?d?.m?n/; abbreviated BWS) is an overgrowth disorder usually... more...

GeneReviews: NBK1394

Clinical features from OMIM:

130650

Search NIH Clinical Center for Beckwith-Wiedemann Syndrome

Search GEO for disease gene expression data for Beckwith-Wiedemann Syndrome.