Early onset or syndromic epilepsy
Gene: EIF2S3
XLR MEHMO syndrome - mentasl retardation, epileptic seizures, hypogonadsm and hypogenitalism, microcephaly and obesity - life expectancy less than 2 years. Moortgat et al, 2016 - 2 teenage mat half brothers, unrelated Belgian parents - 1 developed seizures aged 9 months, the other didn't. A male infant from a second family - Spanish origin - onset of seizures at 10 months and died at 12 months, also 3 other male family members reported to have had a similar phenotype with early death2 diff hemizygous variants identified in these families - 1 missense and 1 fs - more severe pheno with this one. Skopkova et al, 2017 - 3 additional patients with MEHMO - 2 buys from nonconsang Slovakian families (both had epileptic seizures) and a 5 year old boy from nonconsang US family (no seizures) and also the original patient reported by Steinmuller et al, 1998 who had seizures - the same fs seen in 3 families and a missense in the other (milder pheno). 6 families in total 5/6 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
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
MEHMO syndrome, 300148
Publications
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
Comment on list classification: Updated rating from Amber to Green: Probable rating in Gene2Phenotype for 'Syndromic ID with severe microcephaly' but sufficient unrelated cases (>3) of seizures in MEHMO patients from literature (PMIDs 23063529,27333055,28055140).Created: 29 Nov 2018, 10:43 a.m.
Comment on mode of inheritance: X-linked recessive MOI supported by OMIM and literature.Created: 29 Nov 2018, 10:41 a.m.
Skopkova et al 2017 (PMID:28055140) identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. Two of the families had members with seizures amongst their phenotypes.Created: 29 Nov 2018, 10:39 a.m.
Moortgat et al, 2016 (PMID:27333055) examined syndromic intellectual disability in two unrelated families with suspected X-linked inheritance. In both families, affected males presented with severe intellectual disability, microcephaly, growth retardation, and epilepsy in most individuals. A missense variant(c.777T>G p.(Ile259Met)) and a frameshift variant (c.1394_1397del p.(Ile465Serfs*4)) were identified in the EIF2S3 gene in the hemizygous state in affected patients, and in the heterozygous states female obligate carriers.Created: 29 Nov 2018, 10:39 a.m.
Borck et al., 2012 (PMID:23063529) ascertained a family of Morocco Jewish ancestry in which three male individuals were affected by X-linked intellectual disability (ID). Individual III:2 had generalized seizures.Created: 29 Nov 2018, 10:38 a.m.
Steinmuller et al 1998 (PMID:9781023) describe MEHMO syndrome with clinical hallmarks of mental retardation, epileptic seizures, hypogonadism, and -genitalism, microcephaly and obesity. They studied one large family with X-linked recessive inheritance (5 males affected, including 3 deceased and 1 terminated pregnancy). They don't identify the gene itself, but link the disease to a region of the X-chromosome.Created: 29 Nov 2018, 10:30 a.m.
Seizures are a feature of this intellectual disability syndrome.Created: 13 Aug 2018, 11:41 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
MEHMO syndrome, MIM#300148
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to EIF2S3.
Source NHS GMS was added to EIF2S3.
Zornitza Stark: Seizures are a feature of this
Gene: eif2s3 has been classified as Green List (High Evidence).
Gene: eif2s3 has been classified as Green List (High Evidence).
Mode of inheritance for gene: EIF2S3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EIF2S3 were set to
Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, 300148
Expert Review Amber was added to EIF2S3. Panel: Genetic Epilepsy Syndromes
EIF2S3 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
EIF2S3 was created by Sarah Leigh