Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders
Gene: CHD8
Comment on list classification: Changed rating from Red to Green due to expert external reviewCreated: 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From abstract (unpublished) Tatton-Brown et al (2017)(http://conf.hinxton.wellcome.ac.uk/advancedcourses/GRD2017Abstactbook.pdf) Human overgrowth syndromes (OGID) are a nebulous group of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 macrocephalyCreated: 31 Mar 2017, 5:21 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
{Autism, susceptibility to, 18}, 615032
Gene: chd8 has been classified as Green List (High Evidence).
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
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
Publications for gene: CHD8 were set to
Mode of inheritance for gene: CHD8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for CHD8 were set to {Autism, susceptibility to, 18}, 615032; Human overgrowth syndrome type
Phenotypes for CHD8 were set to {Autism, susceptibility to, 18}, 615032
CHD8 was created by LouiseD
CHD8 was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorderspanel. Sources: Other