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| Early onset or syndromic epilepsy v5.6 | KDM6B | Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v5.6 | KDM6B | Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KDM6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v5.6 | KDM6B | Eleanor Williams reviewed gene: KDM6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v5.5 | KDM6B |
Achchuthan Shanmugasundram Source Expert Review Green was added to KDM6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Early onset or syndromic epilepsy v4.67 | KDM6B | Sarah Leigh edited their review of gene: KDM6B: Added comment: 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.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.67 | KDM6B | Sarah Leigh Classified gene: KDM6B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.67 | KDM6B | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.67 | KDM6B | Sarah Leigh Gene: kdm6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.66 | KDM6B | Sarah Leigh Tag Q3_23_promote_green tag was added to gene: KDM6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.66 | KDM6B | Sarah Leigh 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.65 | KDM6B | Sarah Leigh Publications for gene: KDM6B were set to PMID: 37196654 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.62 | KDM6B |
Hannah Robinson 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 Added comment: 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 GMS |
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