Early onset or syndromic epilepsy

Gene: BRAF

I don't know

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 CFC, AD Noonan and AD Leopard syndromes - all of which have phenotypic overlap. Leopard - Sarkozy et al, 2009 - patient whose features included seizures - de novo het missese varint - same variant identified in 2 patients with CFC1. Armour and Allanson 2008 - clinical features of 38 patients with genetically confirmed CFC syndrome - seizures in 49%. Gene will also be on Noonans panel seizures reported at aignificant rate.

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
Adenocarcinoma of lung, somatic 211980; Cardiofaciocutaneous syndrome, 115150; Colorectal cancer, somatic; LEOPARD syndrome, 613707; Melanoma, malignant, somatic; Nonsmall cell lung cancer, somatic; Noonan syndrome, 613706

Publications

• 19206169
• 18042262

Comment when marking as ready: Associated with relevant phenotypes in OMIM and as confirmed Gen2Phen gene for Cardiofaciocutaneous syndrome 115150 & LEOPARD syndrome 3 613707. PMID 18039946 reported seizures in around half of their genetically confirmed Cardiofaciocutaneous syndrome 115150 cases (n=38) and PMID 19206169 reports 11 variants in 9 cases of Cardiofaciocutaneous syndrome 115150, 2 cases of Noonan syndrome 7 613706 and one case of LEOPARD syndrome 3 613707.

Created: 12 Nov 2018, 4:53 p.m.

Comment on mode of pathogenicity: Activating variants responsible for phenotype

Created: 12 Nov 2018, 4:20 p.m.

Green List (high evidence)

Seizures are a common feature of CFC syndrome.

Created: 8 Aug 2018, 1:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiofaciocutaneous syndrome, MIM#115150

Variants in this GENE are reported as part of current diagnostic practice