NDMSCA
MCID: NRD038
MIFTS: 30

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 57 72 6 17
Ndmsca 57 72
Neurodevelopmental Disorder with Microcephaly, Seizures, Cortical Atrophy 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
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® : 57 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) (Updated 20-May-2021)

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 eye, liver and brain, and related phenotypes are dysphagia and global developmental delay

UniProtKB/Swiss-Prot : 72 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 9.7 VARS2 VARS1
2 combined oxidative phosphorylation deficiency 20 9.6 VARS2 VARS1
3 combined oxidative phosphorylation deficiency 12 9.6 VARS2 VARS1
4 perrault syndrome 9.5 VARS2 VARS1

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 dysphagia 31 HP:0002015
2 global developmental delay 31 HP:0001263
3 depressed nasal bridge 31 HP:0005280
4 short nose 31 HP:0003196
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 sloping forehead 31 HP:0000340
11 astigmatism 31 HP:0000483
12 hypoplasia of the corpus callosum 31 HP:0002079
13 cerebellar atrophy 31 HP:0001272
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®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

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
Eye, Liver, Brain

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 VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish. 6 57
30755616 2019
2
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. 57 6
30755602 2019
3
Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy. 57 6
29691655 2018
4
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. 57 6
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. 57 61
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 43)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 VARS1 NM_006295.3(VARS1):c.2074G>C (p.Ala692Pro) SNV Pathogenic 520392 rs747824231 GRCh37: 6:31750138-31750138
GRCh38: 6:31782361-31782361
2 VARS1 NM_006295.3(VARS1):c.1324C>T (p.Arg442Ter) SNV Pathogenic 520393 rs763777257 GRCh37: 6:31753046-31753046
GRCh38: 6:31785269-31785269
3 VARS1 NM_006295.3(VARS1):c.1300C>G (p.Leu434Val) SNV Pathogenic 561994 rs1562303235 GRCh37: 6:31753070-31753070
GRCh38: 6:31785293-31785293
4 VARS1 NM_006295.3(VARS1):c.2464G>A (p.Gly822Ser) SNV Pathogenic 561995 rs376864621 GRCh37: 6:31749338-31749338
GRCh38: 6:31781561-31781561
5 VARS1 NM_006295.3(VARS1):c.1199A>C (p.Gln400Pro) SNV Pathogenic 561996 rs1562303844 GRCh37: 6:31753412-31753412
GRCh38: 6:31785635-31785635
6 VARS1 NM_006295.3(VARS1):c.1325G>A (p.Arg442Gln) SNV Pathogenic 561997 rs762729609 GRCh37: 6:31753045-31753045
GRCh38: 6:31785268-31785268
7 VARS1 NM_006295.3(VARS1):c.219_232dup (p.Leu78fs) Duplication Pathogenic 561998 rs757026184 GRCh37: 6:31762762-31762763
GRCh38: 6:31794985-31794986
8 VARS1 NM_006295.3(VARS1):c.2825G>A (p.Arg942Gln) SNV Pathogenic 561999 rs1336685414 GRCh37: 6:31748318-31748318
GRCh38: 6:31780541-31780541
9 VARS1 NM_006295.3(VARS1):c.1577-2A>G SNV Pathogenic 590284 rs1562301511 GRCh37: 6:31752087-31752087
GRCh38: 6:31784310-31784310
10 VARS1 NM_006295.3(VARS1):c.3192G>A (p.Met1064Ile) SNV Pathogenic 590285 rs1562293093 GRCh37: 6:31747481-31747481
GRCh38: 6:31779704-31779704
11 VARS1 NM_006295.3(VARS1):c.1522G>T (p.Glu508Ter) SNV Pathogenic 998207 GRCh37: 6:31752225-31752225
GRCh38: 6:31784448-31784448
12 VARS1 NM_006295.3(VARS1):c.2653C>T (p.Leu885Phe) SNV Pathogenic 402133 rs1060499734 GRCh37: 6:31748712-31748712
GRCh38: 6:31780935-31780935
13 VARS1 NM_006295.3(VARS1):c.3173G>A (p.Arg1058Gln) SNV Pathogenic 402134 rs769369302 GRCh37: 6:31747500-31747500
GRCh38: 6:31779723-31779723
14 VARS1 NM_006295.3(VARS1):c.181G>T (p.Glu61Ter) SNV Pathogenic 976680 GRCh37: 6:31762814-31762814
GRCh38: 6:31795037-31795037
15 VARS1 NM_006295.3(VARS1):c.3646C>T (p.Gln1216Ter) SNV Pathogenic 1031626 GRCh37: 6:31746824-31746824
GRCh38: 6:31779047-31779047
16 VARS1 NM_006295.3(VARS1):c.1210C>T (p.Arg404Trp) SNV Pathogenic 562000 rs749228986 GRCh37: 6:31753401-31753401
GRCh38: 6:31785624-31785624
17 VARS1 NM_006295.3(VARS1):c.2840G>A (p.Arg947His) SNV Likely pathogenic 559838 rs150882285 GRCh37: 6:31748303-31748303
GRCh38: 6:31780526-31780526
18 VARS1 NM_006295.3(VARS1):c.3344C>G (p.Thr1115Arg) SNV Likely pathogenic 976679 GRCh37: 6:31747258-31747258
GRCh38: 6:31779481-31779481
19 VARS2 , VARS1 NM_006295.3(VARS1):c.1981C>A (p.Pro661Thr) SNV Likely pathogenic 522588 rs1401228799 GRCh37: 6:31750317-31750317
GRCh38: 6:31782540-31782540
20 VARS1 NM_006295.3(VARS1):c.3622C>T (p.Arg1208Ter) SNV Likely pathogenic 873441 GRCh37: 6:31746848-31746848
GRCh38: 6:31779071-31779071
21 VARS1 NM_006295.3(VARS1):c.3650G>A (p.Arg1217His) SNV Likely pathogenic 1029030 GRCh37: 6:31746820-31746820
GRCh38: 6:31779043-31779043
22 VARS1 NM_006295.3(VARS1):c.3355C>T (p.Arg1119Cys) SNV Likely pathogenic 559839 rs149378938 GRCh37: 6:31747247-31747247
GRCh38: 6:31779470-31779470
23 VARS1 NM_006295.3(VARS1):c.1341G>T (p.Met447Ile) SNV Uncertain significance 828121 rs1581645904 GRCh37: 6:31753029-31753029
GRCh38: 6:31785252-31785252
24 VARS1 NM_006295.3(VARS1):c.1747A>C (p.Met583Leu) SNV Uncertain significance 1029023 GRCh37: 6:31750888-31750888
GRCh38: 6:31783111-31783111
25 VARS1 NM_006295.3(VARS1):c.1874C>T (p.Pro625Leu) SNV Uncertain significance 1029024 GRCh37: 6:31750511-31750511
GRCh38: 6:31782734-31782734
26 VARS1 NM_006295.3(VARS1):c.20C>T (p.Ser7Phe) SNV Uncertain significance 1029025 GRCh37: 6:31762975-31762975
GRCh38: 6:31795198-31795198
27 VARS1 NM_006295.3(VARS1):c.2230C>A (p.Pro744Thr) SNV Uncertain significance 1029026 GRCh37: 6:31749875-31749875
GRCh38: 6:31782098-31782098
28 VARS1 NM_006295.3(VARS1):c.2272C>T (p.Arg758Cys) SNV Uncertain significance 1029027 GRCh37: 6:31749699-31749699
GRCh38: 6:31781922-31781922
29 VARS1 NM_006295.3(VARS1):c.3253A>G (p.Ser1085Gly) SNV Uncertain significance 1029028 GRCh37: 6:31747420-31747420
GRCh38: 6:31779643-31779643
30 VARS1 NM_006295.3(VARS1):c.3623G>A (p.Arg1208Gln) SNV Uncertain significance 1029029 GRCh37: 6:31746847-31746847
GRCh38: 6:31779070-31779070
31 VARS1 NM_006295.3(VARS1):c.3656G>A (p.Arg1219Gln) SNV Uncertain significance 1029031 GRCh37: 6:31746814-31746814
GRCh38: 6:31779037-31779037
32 VARS1 NM_006295.3(VARS1):c.611T>C (p.Leu204Pro) SNV Uncertain significance 1029032 GRCh37: 6:31760584-31760584
GRCh38: 6:31792807-31792807
33 VARS1 NM_006295.3(VARS1):c.1331G>A (p.Cys444Tyr) SNV Uncertain significance 1031620 GRCh37: 6:31753039-31753039
GRCh38: 6:31785262-31785262
34 VARS1 NM_006295.3(VARS1):c.1417C>T (p.Arg473Cys) SNV Uncertain significance 1031621 GRCh37: 6:31752422-31752422
GRCh38: 6:31784645-31784645
35 VARS1 NM_006295.3(VARS1):c.1639G>T (p.Val547Leu) SNV Uncertain significance 1031622 GRCh37: 6:31752023-31752023
GRCh38: 6:31784246-31784246
36 VARS1 NM_006295.3(VARS1):c.2735C>A (p.Ala912Glu) SNV Uncertain significance 1031623 GRCh37: 6:31748544-31748544
GRCh38: 6:31780767-31780767
37 VARS1 NM_006295.3(VARS1):c.32A>C (p.Asp11Ala) SNV Uncertain significance 1031624 GRCh37: 6:31762963-31762963
GRCh38: 6:31795186-31795186
38 VARS1 NM_006295.3(VARS1):c.3386G>A (p.Arg1129Gln) SNV Uncertain significance 1031625 GRCh37: 6:31747216-31747216
GRCh38: 6:31779439-31779439
39 VARS1 NM_006295.3(VARS1):c.1014G>T (p.Met338Ile) SNV Uncertain significance 873442 GRCh37: 6:31759473-31759473
GRCh38: 6:31791696-31791696
40 VARS1 NM_006295.3(VARS1):c.3655C>T (p.Arg1219Trp) SNV Uncertain significance 1031627 GRCh37: 6:31746815-31746815
GRCh38: 6:31779038-31779038
41 VARS1 NM_006295.3(VARS1):c.721C>T (p.Arg241Trp) SNV Uncertain significance 1031628 GRCh37: 6:31760234-31760234
GRCh38: 6:31792457-31792457
42 VARS1 NM_006295.3(VARS1):c.3695C>A (p.Pro1232Gln) SNV Uncertain significance 996552 GRCh37: 6:31746775-31746775
GRCh38: 6:31778998-31778998
43 VARS1 NM_006295.3(VARS1):c.2086G>C (p.Gly696Arg) SNV Uncertain significance 996554 GRCh37: 6:31750126-31750126
GRCh38: 6:31782349-31782349

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
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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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