Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

NDMSCA MCID: NRD038 MIFTS: 30	Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy (NDMSCA) Categories: Genetic diseases, Neuronal diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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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:

MalaCards categories:
Global: Genetic diseases
Anatomical: Neuronal diseases

See all MalaCards categories (disease lists)

External Ids:

OMIM® ⁵⁷ 617802

MeSH ⁴⁴ D065886

MedGen ⁴¹ C4540493 CN679649

EFO ¹⁷ EFO_0009644

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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.

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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

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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 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)

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

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

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

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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

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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	Siekierska A...De Jonghe P	30755616	2019
2	Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. ⁵⁷ ⁶	Friedman J...Gleeson JG	30755602	2019
3	Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy. ⁵⁷ ⁶	Stephen J...Malicdan MCV	29691655	2018
4	Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. ⁵⁷ ⁶	Karaca E...Lupski JR	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	Okur V...Chung WK	30275004	2018

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

Genes related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	VARS1	Valyl-TRNA Synthetase 1	Protein Coding	944.71	Molecular basis known ⁵⁷ Pathogenic ⁶ Likely pathogenic ⁶ GeneCards inferred via : Disorders Variants (show sections)	26539891 30755616
2	VARS2	Valyl-TRNA Synthetase 2, Mitochondrial	Protein Coding	32.78	Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)

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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

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

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

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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	tRNA Aminoacylation ⁶⁵ Show member pathways Aminoacyl-tRNA biosynthesis ³⁶ Cytosolic tRNA aminoacylation ⁶⁵ Mitochondrial tRNA aminoacylation ⁶⁵ Pyrophosphate hydrolysis ⁶⁵ SeMet incorporation into proteins ⁶⁵	10.87	VARS2 VARS1

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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

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⁷⁰ UMLS

⁷¹ UMLS via Orphanet

⁷² UniProtKB/Swiss-Prot

⁷³ Wikipedia

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

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

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

Characteristics:

OMIM®:

HPO:

Classifications:

External Ids:

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

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:

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

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

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

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

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:

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

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

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

Genes related to Neurodevelopmental Disorder with Microcephaly, Seizures, and Cortical Atrophy (1 elite genes):

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

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

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

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:

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:

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

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