Early onset or syndromic epilepsy
Gene: HRAS
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
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
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.
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
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to HRAS.
Source NHS GMS was added to HRAS.
Zornitza Stark: Seizures are a feature in abou
Gene: hras has been classified as Green List (High Evidence).
Publications for gene: HRAS were set to
Gene: hras has been classified as Green List (High Evidence).
Mode of inheritance for gene: HRAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HRAS were changed from Costello syndrome, 218040 to Costello syndrome, 218040; Schimmelpenning-Feuerstein-Mims syndrome, 218040
Phenotypes for gene: HRAS were changed from to Costello syndrome, 218040
Expert Review Amber was added to HRAS. Panel: Genetic Epilepsy Syndromes
HRAS was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
HRAS was created by Sarah Leigh