NDMSCA
MCID: NRD038
MIFTS: 29

Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy (NDMSCA)

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

MalaCards integrated aliases for Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy:

Name: Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy 56 73 6 17
Ndmsca 56 73
Neurodevelopmental Disorder with Microcephaly, Seizures, Cortical Atrophy 39

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
progressive disorder
early death may occur


HPO:

31
neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive


Classifications:



Summaries for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

OMIM : 56 Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy (NDMSCA) is an autosomal recessive disorder characterized by severe global developmental delay with poor motor and intellectual function apparent soon after birth, as well as postnatal progressive microcephaly. Most patients develop early-onset, frequent, and often intractable seizures, compatible with an epileptic encephalopathy. Other features include poor feeding, poor overall growth, absent speech, poor or absent eye contact, inability to achieve walking, hypotonia, and peripheral spasticity. Brain imaging usually shows progressive cerebral atrophy, thin corpus callosum, and abnormalities in myelination. Death in childhood may occur (summary by Siekierska et al., 2019). (617802)

MalaCards based summary : Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy, also known as ndmsca, is related to combined oxidative phosphorylation deficiency 2 and combined oxidative phosphorylation deficiency 20. An important gene associated with Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy is VARS1 (Valyl-TRNA Synthetase 1), and among its related pathways/superpathways is tRNA Aminoacylation. Affiliated tissues include brain, eye and liver, and related phenotypes are global developmental delay and depressed nasal bridge

UniProtKB/Swiss-Prot : 73 Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy: An autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, intellectual disability, severe microcephaly, and cortical atrophy.

Related Diseases for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Diseases related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 combined oxidative phosphorylation deficiency 2 9.5 VARS2 VARS1
2 combined oxidative phosphorylation deficiency 20 9.5 VARS2 VARS1
3 combined oxidative phosphorylation deficiency 12 9.5 VARS2 VARS1
4 perrault syndrome 9.4 VARS2 VARS1
5 mitochondrial metabolism disease 9.2 VARS2 VARS1

Graphical network of the top 20 diseases related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy:



Diseases related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy

Symptoms & Phenotypes for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Human phenotypes related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 HP:0001263
2 depressed nasal bridge 31 HP:0005280
3 short nose 31 HP:0003196
4 dysphagia 31 HP:0002015
5 micrognathia 31 HP:0000347
6 low-set ears 31 HP:0000369
7 myopia 31 HP:0000545
8 cerebral cortical atrophy 31 HP:0002120
9 long eyelashes 31 HP:0000527
10 cerebellar atrophy 31 HP:0001272
11 sloping forehead 31 HP:0000340
12 astigmatism 31 HP:0000483
13 hypoplasia of the corpus callosum 31 HP:0002079
14 intellectual disability, profound 31 HP:0002187
15 generalized hypotonia 31 HP:0001290
16 inability to walk 31 HP:0002540
17 progressive microcephaly 31 HP:0000253
18 small anterior fontanelle 31 HP:0000237
19 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Nose:
short nose
flat nasal bridge

Head And Neck Ears:
low-set ears

Neurologic Central Nervous System:
cerebellar atrophy
intellectual disability, profound
inability to walk
thin corpus callosum
delayed psychomotor development, profound
more
Muscle Soft Tissue:
hypotonia, generalized

Skeletal:
distal contractures

Head And Neck Face:
micrognathia
sloping forehead

Head And Neck Eyes:
myopia
long eyelashes
astigmatism

Abdomen Gastrointestinal:
swallowing difficulties

Head And Neck Head:
small anterior fontanel
microcephaly, progressive (up to -9 sd)

Laboratory Abnormalities:
elevation of liver enzymes, transient (in some patients)

Clinical features from OMIM:

617802

Drugs & Therapeutics for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy

Genetic Tests for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Anatomical Context for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

MalaCards organs/tissues related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy:

40
Brain, Eye, Liver

Publications for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Articles related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy:

# Title Authors PMID Year
1
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. 56 6
30755602 2019
2
Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish. 56 6
30755616 2019
3
Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy. 56 6
29691655 2018
4
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. 6 56
26539891 2015
5
Biallelic variants in VARS in a family with two siblings with intellectual disability and microcephaly: case report and review of the literature. 61 56
30275004 2018

Variations for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

ClinVar genetic disease variations for Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy:

6 (show all 19) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VARS1 NM_006295.3(VARS1):c.2074G>C (p.Ala692Pro)SNV Pathogenic 520392 rs747824231 6:31750138-31750138 6:31782361-31782361
2 VARS1 NM_006295.3(VARS1):c.1324C>T (p.Arg442Ter)SNV Pathogenic 520393 rs763777257 6:31753046-31753046 6:31785269-31785269
3 VARS1 NM_006295.3(VARS1):c.2825G>A (p.Arg942Gln)SNV Pathogenic 561999 rs1336685414 6:31748318-31748318 6:31780541-31780541
4 VARS1 NM_006295.3(VARS1):c.2464G>A (p.Gly822Ser)SNV Pathogenic 561995 rs376864621 6:31749338-31749338 6:31781561-31781561
5 VARS1 NM_006295.3(VARS1):c.1325G>A (p.Arg442Gln)SNV Pathogenic 561997 rs762729609 6:31753045-31753045 6:31785268-31785268
6 VARS1 NM_006295.3(VARS1):c.1300C>G (p.Leu434Val)SNV Pathogenic 561994 rs1562303235 6:31753070-31753070 6:31785293-31785293
7 VARS1 NM_006295.3(VARS1):c.1199A>C (p.Gln400Pro)SNV Pathogenic 561996 rs1562303844 6:31753412-31753412 6:31785635-31785635
8 VARS1 NM_006295.3(VARS1):c.219_232dup (p.Leu78fs)duplication Pathogenic 561998 rs757026184 6:31762762-31762763 6:31794985-31794986
9 VARS1 NM_006295.3(VARS1):c.1577-2A>GSNV Pathogenic 590284 rs1562301511 6:31752087-31752087 6:31784310-31784310
10 VARS1 NM_006295.3(VARS1):c.3192G>A (p.Met1064Ile)SNV Pathogenic 590285 rs1562293093 6:31747481-31747481 6:31779704-31779704
11 VARS1 NM_006295.3(VARS1):c.3173G>A (p.Arg1058Gln)SNV Likely pathogenic 402134 rs769369302 6:31747500-31747500 6:31779723-31779723
12 VARS1 NM_006295.3(VARS1):c.2653C>T (p.Leu885Phe)SNV Likely pathogenic 402133 rs1060499734 6:31748712-31748712 6:31780935-31780935
13 VARS1 NM_006295.3(VARS1):c.3622C>T (p.Arg1208Ter)SNV Likely pathogenic 873441 6:31746848-31746848 6:31779071-31779071
14 VARS1 , VARS2 NM_006295.3(VARS1):c.1981C>A (p.Pro661Thr)SNV Likely pathogenic 522588 rs1401228799 6:31750317-31750317 6:31782540-31782540
15 VARS1 NM_006295.3(VARS1):c.3355C>T (p.Arg1119Cys)SNV Likely pathogenic 559839 rs149378938 6:31747247-31747247 6:31779470-31779470
16 VARS1 NM_006295.3(VARS1):c.2840G>A (p.Arg947His)SNV Likely pathogenic 559838 rs150882285 6:31748303-31748303 6:31780526-31780526
17 VARS1 NM_006295.3(VARS1):c.1210C>T (p.Arg404Trp)SNV Conflicting interpretations of pathogenicity 562000 rs749228986 6:31753401-31753401 6:31785624-31785624
18 VARS1 NM_006295.3(VARS1):c.1014G>T (p.Met338Ile)SNV Uncertain significance 873442 6:31759473-31759473 6:31791696-31791696
19 VARS1 NM_006295.3(VARS1):c.1341G>T (p.Met447Ile)SNV Uncertain significance 828121 6:31753029-31753029 6:31785252-31785252

Expression for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Search GEO for disease gene expression data for Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy.

Pathways for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Pathways related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.87 VARS2 VARS1

GO Terms for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

Biological processes related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.26 VARS2 VARS1
2 tRNA aminoacylation for protein translation GO:0006418 9.16 VARS2 VARS1
3 aminoacyl-tRNA metabolism involved in translational fidelity GO:0106074 8.96 VARS2 VARS1
4 valyl-tRNA aminoacylation GO:0006438 8.62 VARS2 VARS1

Molecular functions related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ligase activity GO:0016874 9.26 VARS2 VARS1
2 aminoacyl-tRNA ligase activity GO:0004812 9.16 VARS2 VARS1
3 aminoacyl-tRNA editing activity GO:0002161 8.96 VARS2 VARS1
4 valine-tRNA ligase activity GO:0004832 8.62 VARS2 VARS1

Sources for Neurodevelopmental Disorder with Microcephaly, Seizures, and...

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
Content
Loading form....