MEHMO
MCID: MHM001
MIFTS: 47

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 56 12 52 58 73 36 29 13 6 43 15
Mental Retardation, Epileptic Seizures, Hypogonadism and Hypogenitalism, Microcephaly, and Obesity 56 12 73 39 71
Mrxs20 56 12 73
Mrxs25 56 12 73
Mehmo 56 52 73
X-Linked Intellectual Disability-Epileptic Seizures-Hypogenitalism-Microcephaly-Obesity Syndrome 12 58
Mental Retardation, X-Linked, Syndromic, Borck Type 56 73
Mental Retardation, X-Linked, Syndromic 20 56 73
Mental Retardation, X-Linked, Syndromic 25 56 73
Mrxsbrk 56 73
Intellectual Disability, Epileptic Seizures, Hypogonadism and Hypogenitalism, Microcephaly, and Obesity 52
Mental Retardation, X-Linked, Syndromic, Borck Type; Mrxsbrk 56
Mental Retardation, X-Linked, Syndromic 20; Mrxs20 56
Mental Retardation, X-Linked, Syndromic 25; Mrxs25 56
Syndromic X-Linked Mental Retardation 20 12
Syndromic X-Linked Mental Retardation 25 12
X-Linked Mehmo Syndrome 52

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:

56
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

NIH Rare Diseases : 52 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. Visit the Orphanet disease page for more resources.

MalaCards based summary : Mehmo Syndrome, also known as mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity, is related to visual epilepsy and seizure disorder. 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 Apoptotic Pathways in Synovial Fibroblasts. Affiliated tissues include brain, pancreas and pituitary, and related phenotypes are thick vermilion border and microcephaly

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 : 73 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 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 thick vermilion border 58 31 hallmark (90%) Very frequent (99-80%) HP:0012471
2 microcephaly 58 31 very rare (1%) Very frequent (99-80%) HP:0000252
3 eeg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0002353
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 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
14 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
15 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
16 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
17 hyperreflexia 58 31 very rare (1%) Frequent (79-30%) HP:0001347
18 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
19 downturned corners of mouth 58 31 frequent (33%) Frequent (79-30%) HP:0002714
20 tapered finger 58 31 frequent (33%) Frequent (79-30%) HP:0001182
21 agitation 58 31 frequent (33%) Frequent (79-30%) HP:0000713
22 seizure 31 very rare (1%) HP:0001250
23 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
24 global developmental delay 31 very rare (1%) HP:0001263
25 spasticity 31 very rare (1%) HP:0001257
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 macrotia 31 HP:0000400
32 widely spaced teeth 31 HP:0000687
33 delayed speech and language development 31 HP:0000750
34 seizures 58 Frequent (79-30%)
35 delayed puberty 31 HP:0000823
36 hypoglycemia 31 HP:0001943
37 strabismus 31 HP:0000486
38 cleft palate 31 HP:0000175
39 myopia 31 HP:0000545
40 open mouth 31 HP:0000194
41 long face 31 HP:0000276
42 long philtrum 31 HP:0000343
43 ventriculomegaly 31 HP:0002119
44 hypoplasia of penis 58 Very frequent (99-80%)
45 gait ataxia 31 HP:0002066
46 babinski sign 31 HP:0003487
47 depressed nasal tip 31 HP:0000437
48 hypoplasia of the corpus callosum 31 HP:0002079
49 spastic tetraparesis 31 HP:0001285
50 aggressive behavior 31 HP:0000718

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
intellectual disability
global developmental delay
spasticity
hyperreflexia
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:
autistic features
aggression
behavioral abnormalities

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

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

26 (show top 50) (show all 52)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased NANOG protein expression GR00184-A-3 10.72 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
2 Decreased NANOG protein expression GR00184-A-6 10.72 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
3 Decreased NANOG protein expression GR00184-A-8 10.72 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
4 Decreased OCT4 protein expression GR00184-A-2 10.67 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
5 Decreased OCT4 protein expression GR00184-A-5 10.67 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
6 Decreased OCT4 protein expression GR00184-A-7 10.67 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-104 10.34 EIF2B2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.34 EIF2B1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-109 10.34 EIF2B2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-110 10.34 PPP1R15B
11 Increased shRNA abundance (Z-score > 2) GR00366-A-116 10.34 EIF2B4
12 Increased shRNA abundance (Z-score > 2) GR00366-A-12 10.34 EIF2B2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.34 EIF2B2 EIF2B3 EIF2B5
14 Increased shRNA abundance (Z-score > 2) GR00366-A-122 10.34 EIF2B1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-124 10.34 EIF2B5
16 Increased shRNA abundance (Z-score > 2) GR00366-A-132 10.34 PPP1R15B
17 Increased shRNA abundance (Z-score > 2) GR00366-A-142 10.34 PPP1R15B
18 Increased shRNA abundance (Z-score > 2) GR00366-A-145 10.34 EIF2B5 EIF2B1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.34 EIF2B5
20 Increased shRNA abundance (Z-score > 2) GR00366-A-153 10.34 EIF2B4
21 Increased shRNA abundance (Z-score > 2) GR00366-A-162 10.34 EIF2B1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-165 10.34 EIF2B1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-176 10.34 EIF2B1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-178 10.34 EIF2B4
25 Increased shRNA abundance (Z-score > 2) GR00366-A-180 10.34 EIF2B4
26 Increased shRNA abundance (Z-score > 2) GR00366-A-20 10.34 EIF2B2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-202 10.34 EIF2B2
28 Increased shRNA abundance (Z-score > 2) GR00366-A-208 10.34 EIF2B3
29 Increased shRNA abundance (Z-score > 2) GR00366-A-28 10.34 PPP1R15B
30 Increased shRNA abundance (Z-score > 2) GR00366-A-33 10.34 EIF2B5
31 Increased shRNA abundance (Z-score > 2) GR00366-A-4 10.34 EIF2B1
32 Increased shRNA abundance (Z-score > 2) GR00366-A-69 10.34 EIF2B2
33 Increased shRNA abundance (Z-score > 2) GR00366-A-70 10.34 PPP1R15B
34 Increased shRNA abundance (Z-score > 2) GR00366-A-71 10.34 PPP1R15B
35 Increased shRNA abundance (Z-score > 2) GR00366-A-76 10.34 EIF2B2
36 Increased shRNA abundance (Z-score > 2) GR00366-A-80 10.34 PPP1R15B
37 Increased shRNA abundance (Z-score > 2) GR00366-A-81 10.34 EIF2B4
38 Increased shRNA abundance (Z-score > 2) GR00366-A-84 10.34 PPP1R15B
39 Increased shRNA abundance (Z-score > 2) GR00366-A-89 10.34 EIF2B1
40 Decreased POU5F1-GFP protein expression GR00184-A-1 10.28 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2 PPP1R15B
41 Decreased POU5F1-GFP protein expression GR00184-A-4 10.28 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2S2
42 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 10 EIF2B4
43 Decreased shRNA abundance (Z-score < -2) GR00366-A-135 10 EIF2B2
44 Decreased shRNA abundance (Z-score < -2) GR00366-A-137 10 PPP1R15B
45 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 10 PPP1R15B
46 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10 EIF2B2 EIF2B4 PPP1R15B
47 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 10 EIF2B4
48 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10 PPP1R15B
49 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 10 EIF2B2
50 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 10 PPP1R15B

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 13)
# Title Authors PMID Year
1
EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO. 56 6 61
28055140 2017
2
Two novel EIF2S3 mutations associated with syndromic intellectual disability with severe microcephaly, growth retardation, and epilepsy. 6 56
27333055 2016
3
eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. 6 56
23063529 2012
4
MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, Microcephaly, Obesity): a new X-linked mitochondrial disorder. 56
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. 56
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. 56
9781023 1998
7
[Microencephalic nanism, severe retardation, hypertonia, obesity, and hypogonadism in two brothers: a new syndrome?]. 56
2635712 1989
8
Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB. 61
31836389 2020
9
Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation. 61
30878599 2019
10
MEHMO syndrome and the link between brain, pituitary and pancreas. 61
30954456 2019
11
MEHMO syndrome mutation EIF2S3-I259M impairs initiator Met-tRNAiMet binding to eukaryotic translation initiation factor eIF2. 61
30517694 2019
12
Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome. 61
29303605 2018
13
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 GRCh37 Pos GRCh38 Pos
1 EIF2S3 NM_001415.4(EIF2S3):c.665T>C (p.Ile222Thr)SNV Pathogenic 267205 rs886040855 X:24082345-24082345 X:24064228-24064228
2 EIF2S3 NM_001415.4(EIF2S3):c.777T>G (p.Ile259Met)SNV Pathogenic 267206 rs886040856 X:24084119-24084119 X:24066002-24066002
3 EIF2S3 NM_001415.4(EIF2S3):c.1394_1397del (p.Ile465fs)deletion Pathogenic/Likely pathogenic 265789 rs886040857 X:24094874-24094877 X:24076757-24076760
4 EIF2S3 NM_001415.4(EIF2S3):c.431C>T (p.Thr144Ile)SNV Likely pathogenic 488501 rs751468976 X:24078252-24078252 X:24060135-24060135
5 EIF2S3 NM_001415.4(EIF2S3):c.433A>G (p.Met145Val)SNV Likely pathogenic 804299 X:24078254-24078254 X:24060137-24060137
6 EIF2S3 NM_001415.4(EIF2S3):c.324T>A (p.Ser108Arg)SNV Uncertain significance 265790 rs1057515578 X:24075812-24075812 X:24057695-24057695

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

73
# 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
13.48 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
2
Show member pathways
13.47 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
3
Show member pathways
13.45 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
4
Show member pathways
13.38 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
5
Show member pathways
12.85 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
6
Show member pathways
12.54 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
7
Show member pathways
12.47 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
8
Show member pathways
12.46 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
9 12.41 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
10 11.76 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
11
Show member pathways
10.95 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 2B complex GO:0005851 9.02 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
2 eukaryotic translation initiation factor 2 complex GO:0005850 8.96 EIF2S3 EIF2S2

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 T cell receptor signaling pathway GO:0050852 9.8 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
2 translation GO:0006412 9.8 EIF2S3 EIF2S2 EIF2B5 EIF2B4 EIF2B3 EIF2B2
3 response to glucose GO:0009749 9.77 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
4 response to peptide hormone GO:0043434 9.72 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
5 myelination GO:0042552 9.65 EIF2B5 EIF2B4 EIF2B2
6 ovarian follicle development GO:0001541 9.63 EIF2B5 EIF2B4 EIF2B2
7 cellular metabolic process GO:0044237 9.61 EIF2B4 EIF2B2 EIF2B1
8 response to heat GO:0009408 9.55 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
9 hippocampus development GO:0021766 9.52 EIF2B5 EIF2B3
10 regulation of translational initiation GO:0006446 9.51 EIF2B2 EIF2B1
11 formation of translation preinitiation complex GO:0001731 9.49 EIF2S3 EIF2S2
12 oligodendrocyte development GO:0014003 9.35 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
13 translational initiation GO:0006413 9.17 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 translation initiation factor binding GO:0031369 9.43 EIF2S2 EIF2B5 EIF2B4
2 guanyl-nucleotide exchange factor activity GO:0005085 9.35 EIF2B5 EIF2B4 EIF2B3 EIF2B2 EIF2B1
3 translation factor activity, RNA binding GO:0008135 9.33 EIF2S3 EIF2S2 EIF2B3
4 translation initiation factor activity GO:0003743 9.17 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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