MEHMO
MCID: MHM001
MIFTS: 48

Mehmo Syndrome (MEHMO)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mehmo Syndrome

MalaCards integrated aliases for Mehmo Syndrome:

Name: Mehmo Syndrome 57 12 20 58 72 36 29 13 6 44 15
Mental Retardation, Epileptic Seizures, Hypogonadism and Hypogenitalism, Microcephaly, and Obesity 57 12 72 39 70
X-Linked Intellectual Disability-Epileptic Seizures-Hypogenitalism-Microcephaly-Obesity Syndrome 12 20 58
Mrxs20 57 12 72
Mrxs25 57 12 72
Mehmo 57 20 72
Mental Retardation, X-Linked, Syndromic, Borck Type 57 72
Mental Retardation, X-Linked, Syndromic 20 57 72
Mental Retardation, X-Linked, Syndromic 25 57 72
Mrxsbrk 57 72
Intellectual Disability, Epileptic Seizures, Hypogonadism and Hypogenitalism, Microcephaly, and Obesity 20
Mental Retardation, X-Linked, Syndromic, Borck Type; Mrxsbrk 57
Mental Retardation, X-Linked, Syndromic 20; Mrxs20 57
Mental Retardation, X-Linked, Syndromic 25; Mrxs25 57
Syndromic X-Linked Mental Retardation 20 12
Syndromic X-Linked Mental Retardation 25 12
X-Linked Mehmo Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
mehmo syndrome
Inheritance: Mitochondrial inheritance,X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
variable severity
obligate female carriers are unaffected
three unrelated families have been reported (last curated october 2016)

Inheritance:
x-linked recessive


HPO:

31
mehmo syndrome:
Onset and clinical course variable expressivity
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Mehmo Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85282 Definition MEHMO syndrome is characterised by severe intellectual deficit, epilepsy, microcephaly, hypogenitalism, and obesity. Growth delay and diabetes are also present. To date, it has been described in seven boys, all of whom died within the first two years of life. The causative gene has been localised to the 21.1-22.13p region of the X chromosome and the syndrome appears to result from mitochondrial dysfunction.

MalaCards based summary : Mehmo Syndrome, also known as mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity, is related to alacrima, achalasia, and mental retardation syndrome and microcephaly. An important gene associated with Mehmo Syndrome is EIF2S3 (Eukaryotic Translation Initiation Factor 2 Subunit Gamma), and among its related pathways/superpathways are RNA transport and Viral mRNA Translation. Affiliated tissues include brain, pancreas and pituitary, and related phenotypes are eeg abnormality and thick vermilion border

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by severe intellectual deficit, epilepsy, microcephaly, hypogenitalism and obesity with variable occurrence of growth delay and diabetes that has material basis in variation in the chromosome region Xp22.13-p21.1.

KEGG : 36 MEHMO syndrome is a rare X-linked syndrome characterised by mental retardation, epileptic seizures, hypogenitalism, microcephaly and obesity. It has been reported that MEHMO syndrome is associated with mutations in the X chromosome gene EIF2S3. EIF2S3 encodes the subunit of the eukaryotic translation initiation factor 2 (eIF2).

UniProtKB/Swiss-Prot : 72 MEHMO syndrome: An X-linked recessive mental retardation syndrome characterized by intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity.

More information from OMIM: 300148 PS309510

Related Diseases for Mehmo Syndrome

Graphical network of the top 20 diseases related to Mehmo Syndrome:



Diseases related to Mehmo Syndrome

Symptoms & Phenotypes for Mehmo Syndrome

Human phenotypes related to Mehmo Syndrome:

58 31 (show top 50) (show all 61)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 eeg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0002353
2 thick vermilion border 58 31 hallmark (90%) Very frequent (99-80%) HP:0012471
3 microcephaly 58 31 very rare (1%) Very frequent (99-80%) HP:0000252
4 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
5 cryptorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000028
6 growth delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001510
7 obesity 58 31 very rare (1%) Very frequent (99-80%) HP:0001513
8 micropenis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000054
9 round face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000311
10 severe global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011344
11 large earlobe 58 31 hallmark (90%) Very frequent (99-80%) HP:0009748
12 sloping forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000340
13 hyperreflexia 58 31 very rare (1%) Frequent (79-30%) HP:0001347
14 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
15 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
16 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
17 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
18 downturned corners of mouth 58 31 frequent (33%) Frequent (79-30%) HP:0002714
19 tapered finger 58 31 frequent (33%) Frequent (79-30%) HP:0001182
20 agitation 58 31 frequent (33%) Frequent (79-30%) HP:0000713
21 seizure 31 very rare (1%) HP:0001250
22 hypotonia 31 frequent (33%) HP:0001252
23 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
24 spasticity 31 very rare (1%) HP:0001257
25 global developmental delay 31 very rare (1%) HP:0001263
26 small for gestational age 31 very rare (1%) HP:0001518
27 male hypogonadism 31 very rare (1%) HP:0000026
28 muscular hypotonia of the trunk 31 very rare (1%) HP:0008936
29 birth length less than 3rd percentile 31 very rare (1%) HP:0003561
30 intellectual disability 31 HP:0001249
31 seizures 58 Frequent (79-30%)
32 muscular hypotonia 58 Frequent (79-30%)
33 macrotia 31 HP:0000400
34 widely spaced teeth 31 HP:0000687
35 delayed speech and language development 31 HP:0000750
36 delayed puberty 31 HP:0000823
37 hypoglycemia 31 HP:0001943
38 strabismus 31 HP:0000486
39 cleft palate 31 HP:0000175
40 myopia 31 HP:0000545
41 open mouth 31 HP:0000194
42 long face 31 HP:0000276
43 long philtrum 31 HP:0000343
44 ventriculomegaly 31 HP:0002119
45 hypoplasia of penis 58 Very frequent (99-80%)
46 gait ataxia 31 HP:0002066
47 babinski sign 31 HP:0003487
48 depressed nasal tip 31 HP:0000437
49 hypoplasia of the corpus callosum 31 HP:0002079
50 spastic tetraparesis 31 HP:0001285

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
intellectual disability
spasticity
hyperreflexia
global developmental delay
difficulty walking
more
Growth Height:
short stature

Head And Neck Eyes:
strabismus
myopia

Genitourinary External Genitalia Male:
micropenis
hypogonadism

Head And Neck Nose:
broad nasal tip
flat nasal tip

Neurologic Behavioral Psychiatric Manifestations:
behavioral abnormalities
autistic features
aggression

Growth Other:
poor overall growth

Head And Neck Head:
microcephaly (up to -8 sd)

Head And Neck Teeth:
widely spaced teeth

Endocrine Features:
delayed puberty
hypoglycemia
hypogonadism
growth hormone deficiency

Head And Neck Mouth:
cleft palate
open mouth
drooling
cleft lip

Head And Neck Face:
long face
long philtrum
temporal narrowing
long chin

Muscle Soft Tissue:
hypotonia

Head And Neck Ears:
large ears

Growth Weight:
obesity (1 patient)

Skeletal Feet:
achilles tendon shortening

Clinical features from OMIM®:

300148 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Mehmo Syndrome according to GeneCards Suite gene sharing:

26 (show all 45)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased NANOG protein expression GR00184-A-3 10.62 EIF2B2 EIF2B3 EIF2B4 EIF2S2
2 Decreased NANOG protein expression GR00184-A-6 10.62 EIF2B2 EIF2B3 EIF2B4 EIF2S2
3 Decreased NANOG protein expression GR00184-A-8 10.62 EIF2B2 EIF2B3 EIF2B4 EIF2S2
4 Decreased OCT4 protein expression GR00184-A-2 10.58 EIF2B2 EIF2B3 EIF2B4 EIF2S2
5 Decreased OCT4 protein expression GR00184-A-5 10.58 EIF2B2 EIF2B3 EIF2B4 EIF2S2
6 Decreased OCT4 protein expression GR00184-A-7 10.58 EIF2B2 EIF2B3 EIF2B4 EIF2S2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-104 10.27 EIF2B2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-109 10.27 EIF2B2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-110 10.27 PPP1R15B
10 Increased shRNA abundance (Z-score > 2) GR00366-A-116 10.27 EIF2B4
11 Increased shRNA abundance (Z-score > 2) GR00366-A-12 10.27 EIF2B2
12 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.27 EIF2B2 EIF2B3 EIF2B5
13 Increased shRNA abundance (Z-score > 2) GR00366-A-124 10.27 EIF2B5
14 Increased shRNA abundance (Z-score > 2) GR00366-A-132 10.27 PPP1R15B
15 Increased shRNA abundance (Z-score > 2) GR00366-A-142 10.27 PPP1R15B
16 Increased shRNA abundance (Z-score > 2) GR00366-A-145 10.27 EIF2B5
17 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.27 EIF2B5
18 Increased shRNA abundance (Z-score > 2) GR00366-A-153 10.27 EIF2B4
19 Increased shRNA abundance (Z-score > 2) GR00366-A-178 10.27 EIF2B4
20 Increased shRNA abundance (Z-score > 2) GR00366-A-180 10.27 EIF2B4
21 Increased shRNA abundance (Z-score > 2) GR00366-A-20 10.27 EIF2B2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-202 10.27 EIF2B2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-208 10.27 EIF2B3
24 Increased shRNA abundance (Z-score > 2) GR00366-A-28 10.27 PPP1R15B
25 Increased shRNA abundance (Z-score > 2) GR00366-A-33 10.27 EIF2B5
26 Increased shRNA abundance (Z-score > 2) GR00366-A-69 10.27 EIF2B2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-70 10.27 PPP1R15B
28 Increased shRNA abundance (Z-score > 2) GR00366-A-71 10.27 PPP1R15B
29 Increased shRNA abundance (Z-score > 2) GR00366-A-76 10.27 EIF2B2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-80 10.27 PPP1R15B
31 Increased shRNA abundance (Z-score > 2) GR00366-A-81 10.27 EIF2B4
32 Increased shRNA abundance (Z-score > 2) GR00366-A-84 10.27 PPP1R15B
33 Decreased POU5F1-GFP protein expression GR00184-A-1 10.19 EIF2B2 EIF2B3 EIF2B4 EIF2S2 PPP1R15B
34 Decreased POU5F1-GFP protein expression GR00184-A-4 10.19 EIF2B2 EIF2B3 EIF2B4 EIF2S2
35 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 10 EIF2B4
36 Decreased shRNA abundance (Z-score < -2) GR00366-A-135 10 EIF2B2
37 Decreased shRNA abundance (Z-score < -2) GR00366-A-137 10 PPP1R15B
38 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 10 PPP1R15B
39 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10 EIF2B2 EIF2B4 PPP1R15B
40 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 10 EIF2B4
41 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10 PPP1R15B
42 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 10 EIF2B2
43 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 10 PPP1R15B
44 Decreased shRNA abundance (Z-score < -2) GR00366-A-57 10 EIF2B2 EIF2B4 PPP1R15B
45 Reduced mammosphere formation GR00396-S 9.02 EIF2B2 EIF2B4 EIF2B5 EIF2S2 EIF2S3

Drugs & Therapeutics for Mehmo Syndrome

Search Clinical Trials , NIH Clinical Center for Mehmo Syndrome

Cochrane evidence based reviews: mehmo syndrome

Genetic Tests for Mehmo Syndrome

Genetic tests related to Mehmo Syndrome:

# Genetic test Affiliating Genes
1 Mehmo Syndrome 29 EIF2S3

Anatomical Context for Mehmo Syndrome

MalaCards organs/tissues related to Mehmo Syndrome:

40
Brain, Pancreas, Pituitary

Publications for Mehmo Syndrome

Articles related to Mehmo Syndrome:

(show all 16)
# Title Authors PMID Year
1
EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO. 57 6 61
28055140 2017
2
Two novel EIF2S3 mutations associated with syndromic intellectual disability with severe microcephaly, growth retardation, and epilepsy. 6 57
27333055 2016
3
eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. 6 57
23063529 2012
4
MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, Microcephaly, Obesity): a new X-linked mitochondrial disorder. 57
12032729 2002
5
MEHMO, a novel syndrome: assignment of disease locus to Xp21.1-p22.13. Mental retardation, epileptic seizures, hypogonadism and genitalism, microcephaly, obesity. 57
10482947 1999
6
MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignment of disease locus to xp21.1-p22.13. 57
9781023 1998
7
[Microencephalic nanism, severe retardation, hypertonia, obesity, and hypogonadism in two brothers: a new syndrome?]. 57
2635712 1989
8
Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis. 61
33714664 2021
9
Novel pathogenic EIF2S3 missense variants causing clinically variable MEHMO syndrome with impaired eIF2γ translational function, and literature review. 61
32799315 2020
10
Immunologic phenotype of a child with the MEHMO syndrome. 61
32901502 2020
11
Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB. 61
31836389 2020
12
Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation. 61
30878599 2019
13
MEHMO syndrome and the link between brain, pituitary and pancreas. 61
30954456 2019
14
MEHMO syndrome mutation EIF2S3-I259M impairs initiator Met-tRNAiMet binding to eukaryotic translation initiation factor eIF2. 61
30517694 2019
15
Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome. 61
29303605 2018
16
Overstressed response to EIF2S3 variants in MEHMO syndrome. 61
28301896 2017

Variations for Mehmo Syndrome

ClinVar genetic disease variations for Mehmo Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EIF2S3 NM_001415.4(EIF2S3):c.665T>C (p.Ile222Thr) SNV Pathogenic 267205 rs886040855 GRCh37: X:24082345-24082345
GRCh38: X:24064228-24064228
2 EIF2S3 NM_001415.4(EIF2S3):c.777T>G (p.Ile259Met) SNV Pathogenic 267206 rs886040856 GRCh37: X:24084119-24084119
GRCh38: X:24066002-24066002
3 EIF2S3 NM_001415.4(EIF2S3):c.1394_1397del (p.Ile465fs) Deletion Pathogenic 265789 rs886040857 GRCh37: X:24094874-24094877
GRCh38: X:24076757-24076760
4 EIF2S3 NM_001415.4(EIF2S3):c.433A>G (p.Met145Val) SNV Likely pathogenic 804299 rs1602041478 GRCh37: X:24078254-24078254
GRCh38: X:24060137-24060137
5 EIF2S3 NM_001415.4(EIF2S3):c.431C>T (p.Thr144Ile) SNV Likely pathogenic 488501 rs751468976 GRCh37: X:24078252-24078252
GRCh38: X:24060135-24060135
6 EIF2S3 NM_001415.4(EIF2S3):c.324T>A (p.Ser108Arg) SNV Uncertain significance 265790 rs1057515578 GRCh37: X:24075812-24075812
GRCh38: X:24057695-24057695
7 EIF2S3 NM_001415.4(EIF2S3):c.1183-15A>G SNV Uncertain significance 1033838 GRCh37: X:24091193-24091193
GRCh38: X:24073076-24073076

UniProtKB/Swiss-Prot genetic disease variations for Mehmo Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 EIF2S3 p.Ile222Thr VAR_077139 rs886040855

Expression for Mehmo Syndrome

Search GEO for disease gene expression data for Mehmo Syndrome.

Pathways for Mehmo Syndrome

Pathways related to Mehmo Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 RNA transport hsa03013

Pathways related to Mehmo Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.41 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
2
Show member pathways
13.39 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
3
Show member pathways
13.39 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
4
Show member pathways
13.36 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
5
Show member pathways
12.78 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
6
Show member pathways
12.44 EIF2B5 EIF2B4 EIF2B3 EIF2B2
7
Show member pathways
12.41 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
8
Show member pathways
12.37 EIF2B5 EIF2B4 EIF2B3 EIF2B2
9 12.32 EIF2B5 EIF2B4 EIF2B3 EIF2B2
10 11.7 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
11
Show member pathways
10.89 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2

GO Terms for Mehmo Syndrome

Cellular components related to Mehmo Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 eukaryotic translation initiation factor 2 complex GO:0005850 8.96 EIF2S3 EIF2S2
2 eukaryotic translation initiation factor 2B complex GO:0005851 8.92 EIF2B5 EIF2B4 EIF2B3 EIF2B2

Biological processes related to Mehmo Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 regulation of catalytic activity GO:0050790 9.78 EIF2B5 EIF2B4 EIF2B3 EIF2B2
2 T cell receptor signaling pathway GO:0050852 9.73 EIF2B5 EIF2B4 EIF2B3 EIF2B2
3 response to glucose GO:0009749 9.67 EIF2B5 EIF2B4 EIF2B3 EIF2B2
4 myelination GO:0042552 9.63 EIF2B5 EIF2B4 EIF2B2
5 translation GO:0006412 9.63 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
6 response to peptide hormone GO:0043434 9.62 EIF2B5 EIF2B4 EIF2B3 EIF2B2
7 ovarian follicle development GO:0001541 9.58 EIF2B5 EIF2B4 EIF2B2
8 response to heat GO:0009408 9.56 EIF2B5 EIF2B4 EIF2B3 EIF2B2
9 hippocampus development GO:0021766 9.52 EIF2B5 EIF2B3
10 cellular metabolic process GO:0044237 9.51 EIF2B4 EIF2B2
11 formation of translation preinitiation complex GO:0001731 9.49 EIF2S3 EIF2S2
12 oligodendrocyte development GO:0014003 9.26 EIF2B5 EIF2B4 EIF2B3 EIF2B2
13 translational initiation GO:0006413 9.1 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2

Molecular functions related to Mehmo Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 9.56 EIF2B5 EIF2B4 EIF2B3 EIF2B2
2 translation initiation factor binding GO:0031369 9.33 EIF2S2 EIF2B5 EIF2B4
3 translation factor activity, RNA binding GO:0008135 9.13 EIF2S3 EIF2S2 EIF2B3
4 translation initiation factor activity GO:0003743 9.1 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2

Sources for Mehmo Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....