Early onset or syndromic epilepsy
Gene: KDM6B
KDM6B variants have been associated with relevant phenotype in OMIM and as strong Gen2Phen gene for KDM6B-related developmental disorder (monoallelic). PMID: 37196654 reports that in their cohort, 9/69 (13%) of individuals had seizures.Created: 6 Jul 2023, 9:27 a.m. | Last Modified: 6 Jul 2023, 9:27 a.m.
Panel Version: 4.67
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 6 Jul 2023, 9:21 a.m. | Last Modified: 6 Jul 2023, 9:21 a.m.
Panel Version: 4.67
Information from Rots et al. 2023 (PMID:37196654): According to OMIM, heterozygous variants in KDM6B cause “neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities.” Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.).
In this cohort, 9/69 (13%) of individuals had seizures.
The majority of individuals had de novo variants but 9/85 individuals inherited the variant (five maternal, four paternal) from a mildly affected (developmental delay [DD], learning problems, autism spectrum disorder [ASD]) or clinically unaffected parent.
Sources: NHS GMSCreated: 28 Jun 2023, 7:12 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: kdm6b has been classified as Amber List (Moderate Evidence).
Tag Q3_23_promote_green tag was added to gene: KDM6B.
Phenotypes for gene: KDM6B were changed from Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505; neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790
Publications for gene: KDM6B were set to PMID: 37196654
gene: KDM6B was added gene: KDM6B was added to Early onset or syndromic epilepsy. Sources: NHS GMS Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM6B were set to PMID: 37196654 Phenotypes for gene: KDM6B were set to Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth Penetrance for gene: KDM6B were set to Incomplete Review for gene: KDM6B was set to GREEN gene: KDM6B was marked as current diagnostic