Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders

Gene: CHD8

Green List (high evidence)

CHD8 (chromodomain helicase DNA binding protein 8)
EnsemblGeneIds (GRCh38): ENSG00000100888
EnsemblGeneIds (GRCh37): ENSG00000100888
OMIM: 610528, Gene2Phenotype
CHD8 is in 6 panels

1 review

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changed rating from Red to Green due to expert external review
Created: 31 May 2019, 8:59 a.m.
Review and Green rating from Kate Tatton-Brown April 2017. Paper in press with AJHG. We wil be reporting variants in clinical practice soon.
Created: 31 May 2019, 8:45 a.m.
Recently Human overgrowth syndrome-causing mutations in the gene CHD8 have been identified.
From abstract (unpublished) Tatton-Brown et al (2017)(http://conf.hinxton.wellcome.ac.uk/advancedcourses/GRD2017Abstactbook.pdf) Human overgrowth syndromes (OGID) are a nebulous group of conditions with height and/or head circumference ≥ 2SD above the mean, together with additional phenotypic abnormalities, the commonest of which is intellectual disability. To explore the genetic architecture of human overgrowth syndromes and growth control, we have performed experimental and bioinformatic analyses of 710 individuals with OGID, identifying patients with OGID-causing mutations in genes including NSD1 (240 cases), EZH2 (34 cases), DNMT3A (18 cases), CHD8 (12 cases) and EED (two cases) and HIST1H1E (five cases). Other genes with OGID-causing mutations, identified in the current study, include NFIX (14 cases), GPC3 (two cases) and BRWD3 (seven cases) in addition to the genes encoding components of the PI3K/AKT pathway (PTEN (16 cases); PPP2R5D (three cases); AKT and PIK3CA (one case each).
Created: 31 Mar 2017, 5:57 p.m.
Comment on phenotypes: Not confirmed Gene-Phenotype relationship in OMIM, but {Autism, susceptibility to, 18}, 615032 includes some cases with macrocephaly
Created: 31 Mar 2017, 5:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
{Autism, susceptibility to, 18}, 615032

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Other
Phenotypes
  • {Autism, susceptibility to, 18}, 615032
  • Overgrowth with Intellectual disability
  • Human overgrowth syndrome type
OMIM
610528
Clinvar variants
Variants in CHD8
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

31 May 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: chd8 has been classified as Green List (High Evidence).

31 May 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: CHD8 were changed from Overgrowth with Intellectual disability; Human overgrowth syndrome type to {Autism, susceptibility to, 18}, 615032; Overgrowth with Intellectual disability; Human overgrowth syndrome type

31 May 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: CHD8 were changed from {Autism, susceptibility to, 18}, 615032; Human overgrowth syndrome type to Overgrowth with Intellectual disability; Human overgrowth syndrome type

31 May 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CHD8 were set to

31 May 2019, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: CHD8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

31 Mar 2017, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for CHD8 were set to {Autism, susceptibility to, 18}, 615032; Human overgrowth syndrome type

31 Mar 2017, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for CHD8 were set to {Autism, susceptibility to, 18}, 615032

31 Mar 2017, Gel status: 0

Created

Louise Daugherty (Genomics England Curator)

CHD8 was created by LouiseD

31 Mar 2017, Gel status: 0

Added New Source

Louise Daugherty (Genomics England Curator)

CHD8 was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorderspanel. Sources: Other