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GENATLAS PHENOTYPE
last update : 29-09-2016
Symbol WBS
Location 7q11.23
Name Williams Beuren syndrome
Other name(s)
  • Williams syndrome
  • elfin facies with hypercalcemia
    • Corresponding gene DNAJC30 , ELN , LIMK1 , GTF2I , GTF2IRD1 , EIF4H , TRIM50 , RFC2 , NCF1 , GTF2IRD2 , HIP1 , YWHAG
    Other symbol(s) WS, WMS, DEL7Q11
    Main clinical features
  • characteristic facial features : elfin facies, flat nasal bridge with anteverted nares, wide mouth with fleshy lips, periorbital fullness, epicanthal folds, flat malar region, small mandible and prominent cheeks
  • heart abnormalities, typically supravalvular aortic stenosis and peripheral pulmonary stenosis, hyperacusis, infantile hypercalcemia, short stature and abnormal gait
  • sensorineural hearing loss in a significant number of patients
  • mental retardation
  • behavioral phenotype : hypersociability, deficits in visual-spatial and global processing, preserved language and face processing
  • alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence, associated to combination of an enlarged ventral anterior prefrontal cortex and large bending angle of the corpus callosum (contributing to the the social-affective language defect)
    • Genetic determination chromosomal
    genomic disorder
    Prevalence 1/7500
    Related entries supravalvular aortic stenosis (SVAS)
    Function/system disorder cardiovascular
    mental retardation
    multisystem/generalized
    Type MCA/MR
    Gene product
    Name contiguous gene disorders with deletion encompassing about 28 genes; ELN: structural protein elastin
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
      deletion haploinsufficiency recurrent deletion of 1.55 Mb including 26–28 genes at chromosomal region 7q11.23
      inversion   An inversion polymorphism has recently been identified in 25-33p100 of transmitting BWS parents
      deletion haploinsufficiency a larger ~1.8Mb deletion encompassing GTF2IRD2 with more severely impaired cognitive functioning, PMID: 23118870
    Remark(s)
  • haploinsufficiency for ELN is associated with cardiovascular (SVAS) and connective tissue deficits; GTF2IRD1 could be associated with WS facies and visual-spatial cognition, and GTF2I with social behavior; GTF2I and GTF2IRD1 identified as the main genes responsible for the Williams-Beuren syndrome neurocognitive profile (Antonell 2010)
  • haploinsufficiency of HIP1 and YWHAG might cause the severe neurological and neuropsychological deficits including epilepsy and autistic traits in WBS (PMID: 23756441))
  • mitochondrial dysfunction participates in WBS pathogenesis (PMID: 30318146))
    • Genotype/Phenotype correlations
  • larger distal deletion associated with both WBS and infantile spasms (IS-suggest MAGI2 as a candidate gene for IS (Marshall,08) ; cytogenetically visible deletions with a more severe phenotype and smaller deletions with a milder or incomplete phenotype have also been identified ; segmental duplication also displaying severe expressive language delay ; hypertension was significantly less prevalent in patients with WBS
    • who had the deletion that included NCF1; individuals with classic WS deletions and SERPINA1 genotypes PiMS or PiMZ were more likely than those with a SERPINA1 PiMM genotype to have joint dislocation or scoliosis (Morris 2010)