Early onset or syndromic epilepsy

Gene: HRAS

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 Costello syndrome. Rare multiple congenital anomaly syndrome associated in all cases with a charateristic coarse facies, short stature, distinctive hand postire and appearance, severe feeding diff, failure to thrive. Seizures doesn't appear to be a common feature but has been reported in a few papers: Kawame et al, 2003 - retrospective view of 10 children with Costello syndrome - 5/10 had seizures - suggest that those in the newborn period might be due to hypoglycemic episodes - do not fit into a predictable type and age of onset varied. Delrue et al, 2003 - in this paper they say that electrophysiological abnormalities have been described in Costello and EEG findings available for 49 children -only 20% had seizures. Hennekam et al, 2003 - table 1 73 cases reported in the literature 6/15 had seizures.

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
Congenital myopathy with excess of muscle spindles, 218040; Costello syndrome, 218040; Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, 163200

Publications

• 16170316

Comment on list classification: Promoted from amber to green. There are 3+ cases reporting of unrelated patients with Costello syndrome who have seizures (PMID: 28337834, 27195699, 26888048, 22926243) and all patients have different HRAS variants (heterozygous).

It is also confirmed as being associated with Costello syndrome on OMIM and Gene2Phenotype.

Created: 15 Nov 2018, 2:59 p.m.

Green List (high evidence)

Seizures are a feature in about 20-50% of individuals with Costello syndrome.

Created: 15 Aug 2018, 1:57 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Costello syndrome

Publications

• 14608654, 12605434

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