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GENATLAS PHENOTYPE
last update : 11-06-2018
Symbol BWS
Location 11p15.5
Name Beckwith-Wiedemann syndrome
Other name(s) EMG syndrome, Exomphalos-Macroglossia-Gigantism syndrome
Corresponding gene IGF2 , H19 , CDKN1C , KCNQ1 , KCNQ1OT1
Other symbol(s) BWCR, DUP11PD, UPD11P
Main clinical features
  • overgrowth and tumor-associated disorder
  • characterized by pre- and postnatal overgrowth, macroglossia, omphalocele or other abdominal wall-defects, visceromegaly, embryonic tumors (mainly Wilms tumor), ear creases/pits, renal anomalies, hemihyperplasia, polyhydramnios, prematurity, neonatal hypoglycemia, fetal macrosomia, monozygous twinning
  • the estimated risk for neoplasia is 7.5 % but is variable according to molecular defect. Tumor development is uncommun after 8 years of age
  • development is usually normal unless there is a chromosomal imbalance or a history of hypoxia or untreated hypoglycemia
  • after childhood, complications are infrequent and prognosis is favorable
    • Genetic determination epigenetic
    autosomal dominant
    chromosomal
    Prevalence 1/13700
    Related entries isolated hemihypertrophy
    Function/system disorder multisystem/generalized
    neoplasia
    Type other
    Gene product
    Name multiple genes on the imprinted 11p15 region are involved
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    other     CDKN1C (p57KIP2), 5-10p.100 of sporadic cases, 40p.100 of familial cases
      uniparental disomy   somatic mosaicism for a segmental paternal uniparental disomy in 10-20p.100 of patients
      duplication   partial trisomy of paternal origin in 1p100 of patients
      translocation   balanced translocation of maternal origin with a breakpoint in a critical region, rarely observed
    deletion     microdeletions of LIT1/ KCNQ1OT1 causing silencing of CDKN1C when maternally inherited, no phenotype when paternally inherited
    imprinting defect     loss of imprinting (LOI) of IGF2, H19 hypermethylation and silencing due to a defect in a distal imprinting control element (IC1)
    imprinting defect     loss of methylation of KvDMR1, LOI of KCNQ1OT1/LIT1 and variable LOI of IGF2 due to a defect in a more proximal imprinting control element (IC2)
    imprinting defect     hypermethylation of H19 in idiopathic hemihypertrophy and Wilms tumor, significantly lower than the frequency in BWS and Wilms tumor
    imprinting defect     multilocus LOM
    Remark(s)
  • imprinting Centre 1 (IC1 ) deletion is a cause of familial BWS characterized by dominant maternal transmission and loss of IGF2-H19 imprinting and high risk of developing Wilms tumour ; some patients may present hypomethylation of other maternally imprinted ICRs, mainly PLAGL1 and GNAS
  • maternal ICR1 gain of methylation in 10p100 of BWS cases (Demars 2010)
    • Genotype/Phenotype correlations Hemihypertrophy is strongly associated with UPD, exomphalos with IC2 defect or CDKN1C mutation but not UPD or IC1 defect cases ; risk of neoplasia is significantly higher in UPD and IC1 defect than in IC2 defect and CDKN1C mutation cases (9 percent for all patients vs 24 percent in UPD patients) ; the risk of Wilms tumor is minimal in the IC2 defect subgroup.