Early onset or syndromic epilepsy

Gene: CREBBP

Green List (high evidence)

exon 30 and 31 CREBBP variants cause a syndrome distinct from Rubinstein-Taybi and according to this case series 21% have epilepsy (https://www.ncbi.nlm.nih.gov/pubmed/29460469) seizures are also listed as a feature of Rubinstein-Taybi syndrome.

Created: 7 Oct 2019, 2:15 p.m. | Last Modified: 7 Oct 2019, 2:15 p.m.

Panel Version: 1.352

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 29460469

I don't know

Comment on mode of inheritance: Changed MOI from 'imprinted status unknown' to 'NOT imprinted' to match reviews from GLH experts Tracy Lester and Alisdair McNeill.

Created: 8 Oct 2019, 9:51 a.m. | Last Modified: 8 Oct 2019, 9:51 a.m.

Panel Version: 1.353

The Green rating by Dr Alisdair McNeill (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of CREBBP.

Created: 8 Oct 2019, 9:50 a.m. | Last Modified: 8 Oct 2019, 9:50 a.m.

Panel Version: 1.352

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AD Rubinstein-Taybi syndrome 1 (RSTS1). Multiple congenital anomaly syndrome characterised by mental retardation, postnatal growth defic, microcephaly, broad thumbs and halluces and dysmorhic facial features. No mention of seizures/epilepsy in any if the clinical patient descritipns on OMIM. Ref used on panel app: Bartsch et al, 2010 - family 2 with classic RTS - 1 of the 3 probands (proband 5) had severe complex seizures atr the age if 2 years and a year later a slow growing ganglioma of the brain was surgically removed - the seizures stopped after surgery. Schorrey et al, 2008 - seizure disorder more common in the CREBBP group (15/52 patients).

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Rubinstein-Taybi syndrome, 180849

Publications

• 12566391
• 25599811

Red List (low evidence)

Associated with Rubinstein-Taybi syndrome 1 in OMIM and as confirmed Gen2Phen gene for this phenotype. Seizures are reported as a feature of Rubinstein-Taybi syndrome 1, in a single 2 year old girl who had several complex focal seizures, a slow growing ganglioglioma of the brain (left temporo–medio–basal region) was found a year later, after surgical removal of the tumour her seizures ceased (PMID 20684013). In PMID 18792986 15/52 (29%) cases of Rubinstein-Taybi syndrome with a CREBBP variant had seizures as part of their phenotype.
Sources: Expert list from Ian Berry, Leeds

Created: 8 Nov 2018, 2:38 p.m.

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

Phenotypes
Rubinstein-Taybi syndrome 1 180849

Publications

• 20684013