NEDSPM
MCID: NRD101
MIFTS: 26

Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly (NEDSPM)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neurodevelopmental Disorder with Spastic Paraplegia and...

MalaCards integrated aliases for Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

Name: Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly 57
Mental Retardation, Autosomal Recessive 49 72 29 6
Postnatal Microcephaly-Infantile Hypotonia-Spastic Diplegia-Dysarthria-Intellectual Disability Syndrome 58
Mental Retardation, Autosomal Recessive 49, Formerly; Mrt49, Formerly 57
Neurodevelopmental Disorder with Microcephaly and Spastic Paraplegia 57
Mental Retardation, Autosomal Recessive 49, Formerly 57
Mental Retardation, Autosomal Recessive, Type 49 39
Mrt49, Formerly 57
Nedspm 57
Mrt49 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
onset in the first year of life


HPO:

31
neurodevelopmental disorder with spastic paraplegia and microcephaly:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Neurodevelopmental Disorder with Spastic Paraplegia and...

OMIM® : 57 Neurodevelopmental disorder with spastic paraplegia and microcephaly (NEDSPM) is an autosomal recessive neurologic syndrome characterized by delayed psychomotor development with delayed walking, moderately to severely impaired intellectual development, and poor or absent speech. More severely affected individuals show poor overall growth with progressive microcephaly, axial hypotonia, oromotor dysfunction with drooling, joint contractures, and spastic paraplegia resulting in walking difficulties. Some patients may develop seizures; nonspecific dysmorphic features have also been reported (summary by Hengel et al., 2018 and Ouyang et al., 2019). (616281) (Updated 05-Apr-2021)

MalaCards based summary : Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly, is also known as mental retardation, autosomal recessive 49. An important gene associated with Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly is GPT2 (Glutamic--Pyruvic Transaminase 2). Affiliated tissues include brain, and related phenotypes are intellectual disability and hyperreflexia

UniProtKB/Swiss-Prot : 72 Mental retardation, autosomal recessive 49: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT49 patients show a developmental encephalopathy characterized by rapid onset of failure to thrive and microcephaly, as well as profoundly delayed development.

Related Diseases for Neurodevelopmental Disorder with Spastic Paraplegia and...

Symptoms & Phenotypes for Neurodevelopmental Disorder with Spastic Paraplegia and...

Human phenotypes related to Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

58 31 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
3 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
4 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
5 delayed speech and language development 58 31 frequent (33%) Frequent (79-30%) HP:0000750
6 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
7 low-set ears 58 31 frequent (33%) Frequent (79-30%) HP:0000369
8 hypotelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000601
9 severe muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0006829
10 spastic paraplegia 58 31 frequent (33%) Frequent (79-30%) HP:0001258
11 broad-based gait 58 31 frequent (33%) Frequent (79-30%) HP:0002136
12 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
13 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
14 drooling 58 31 frequent (33%) Frequent (79-30%) HP:0002307
15 nasogastric tube feeding in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0011470
16 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
17 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
18 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
19 abnormal cns myelination 58 31 occasional (7.5%) Occasional (29-5%) HP:0011400
20 narrow forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000341
21 febrile seizure (within the age range of 3 months to 6 years) 31 occasional (7.5%) HP:0002373
22 seizures 58 Occasional (29-5%)
23 spasticity 31 HP:0001257
24 absent speech 31 HP:0001344
25 encephalopathy 31 HP:0001298
26 postnatal microcephaly 31 HP:0005484
27 generalized hypotonia 31 HP:0001290
28 febrile seizures 58 Occasional (29-5%)
29 bilateral tonic-clonic seizure 31 HP:0002069

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
ataxia
dysarthria
global developmental delay
absent speech
more
Skeletal Spine:
scoliosis

Head And Neck Eyes:
strabismus
synophrys
epicanthal folds

Head And Neck Mouth:
drooling
high-arched palate
sialorrhea
oromotor dysfunction

Skeletal:
contractures (in some patients)

Head And Neck Head:
microcephaly, postnatal (up to -6.8 sd)

Growth Other:
failure to thrive
poor overall growth

Growth Height:
short stature

Head And Neck Face:
short philtrum
dysmorphic facial features, nonspecific (in some patients)

Abdomen Gastrointestinal:
poor feeding

Head And Neck Ears:
abnormal helix

Clinical features from OMIM®:

616281 (Updated 05-Apr-2021)

Drugs & Therapeutics for Neurodevelopmental Disorder with Spastic Paraplegia and...

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly

Genetic Tests for Neurodevelopmental Disorder with Spastic Paraplegia and...

Genetic tests related to Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Recessive 49 29 GPT2

Anatomical Context for Neurodevelopmental Disorder with Spastic Paraplegia and...

MalaCards organs/tissues related to Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

40
Brain

Publications for Neurodevelopmental Disorder with Spastic Paraplegia and...

Articles related to Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

# Title Authors PMID Year
1
GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates. 6 57
31471722 2019
2
GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia. 57 6
29882329 2018
3
Novel compound heterozygous mutations in GPT2 linked to microcephaly, and intellectual developmental disability with or without spastic paraplegia. 6 57
29226631 2018
4
Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. 6 57
27601654 2016
5
Loss of function mutation in glutamic pyruvate transaminase 2 (GPT2) causes developmental encephalopathy. 57 6
25758935 2015
6
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery. 6
32214227 2020
7
CNTNAP1 mutations cause CNS hypomyelination and neuropathy with or without arthrogryposis. 6
28374019 2017
8
A Homozygous Mutation in GPT2 Associated with Nonsyndromic Intellectual Disability in a Consanguineous Family from Costa Rica. 57
28130718 2017

Variations for Neurodevelopmental Disorder with Spastic Paraplegia and...

ClinVar genetic disease variations for Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GPT2 NM_133443.4(GPT2):c.70C>T (p.Gln24Ter) SNV Pathogenic 522105 rs1437184398 GRCh37: 16:46918697-46918697
GRCh38: 16:46884785-46884785
2 GPT2 NM_133443.4(GPT2):c.400C>T (p.Arg134Cys) SNV Pathogenic 983537 GRCh37: 16:46934660-46934660
GRCh38: 16:46900748-46900748
3 GPT2 NM_133443.4(GPT2):c.1435G>A (p.Val479Met) SNV Pathogenic 983538 GRCh37: 16:46960903-46960903
GRCh38: 16:46926991-46926991
4 GPT2 NM_133443.4(GPT2):c.1432_1433del (p.Val478fs) Microsatellite Pathogenic 983539 GRCh37: 16:46960897-46960898
GRCh38: 16:46926985-46926986
5 GPT2 NM_133443.4(GPT2):c.812A>C (p.Asn271Thr) SNV Pathogenic 983541 GRCh37: 16:46943831-46943831
GRCh38: 16:46909919-46909919
6 GPT2 NM_133443.4(GPT2):c.775T>C (p.Cys259Arg) SNV Pathogenic 983542 GRCh37: 16:46943794-46943794
GRCh38: 16:46909882-46909882
7 GPT2 NM_133443.4(GPT2):c.1306C>T (p.Gln436Ter) SNV Pathogenic 998334 GRCh37: 16:46958394-46958394
GRCh38: 16:46924482-46924482
8 GPT2 NM_133443.4(GPT2):c.459C>G (p.Ser153Arg) SNV Pathogenic 187856 rs786203999 GRCh37: 16:46940770-46940770
GRCh38: 16:46906858-46906858
9 GPT2 NM_133443.4(GPT2):c.1210C>T (p.Arg404Ter) SNV Pathogenic 254655 rs115352435 GRCh37: 16:46956326-46956326
GRCh38: 16:46922414-46922414
10 GPT2 NM_133443.4(GPT2):c.1177dup (p.Val393fs) Duplication Likely pathogenic 988735 GRCh37: 16:46956291-46956292
GRCh38: 16:46922379-46922380
11 GPT2 NM_133443.4(GPT2):c.1037+5G>A SNV Uncertain significance 997801 GRCh37: 16:46952674-46952674
GRCh38: 16:46918762-46918762
12 GPT2 NM_133443.4(GPT2):c.1172C>T (p.Pro391Leu) SNV Uncertain significance 72070 rs140993544 GRCh37: 16:46956288-46956288
GRCh38: 16:46922376-46922376
13 GPT2 NM_133443.4(GPT2):c.815C>T (p.Pro272Leu) SNV Uncertain significance 254656 rs886038199 GRCh37: 16:46943834-46943834
GRCh38: 16:46909922-46909922
14 GPT2 NM_133443.4(GPT2):c.589A>G (p.Ile197Val) SNV Uncertain significance 1031115 GRCh37: 16:46943608-46943608
GRCh38: 16:46909696-46909696
15 GPT2 NM_133443.4(GPT2):c.371G>C (p.Ser124Thr) SNV Uncertain significance 1031604 GRCh37: 16:46934631-46934631
GRCh38: 16:46900719-46900719
16 GPT2 NM_133443.4(GPT2):c.478C>T (p.Arg160Cys) SNV Uncertain significance 1031605 GRCh37: 16:46940789-46940789
GRCh38: 16:46906877-46906877

UniProtKB/Swiss-Prot genetic disease variations for Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly:

72
# Symbol AA change Variation ID SNP ID
1 GPT2 p.Ser153Arg VAR_073379 rs786203999

Expression for Neurodevelopmental Disorder with Spastic Paraplegia and...

Search GEO for disease gene expression data for Neurodevelopmental Disorder with Spastic Paraplegia and Microcephaly.

Pathways for Neurodevelopmental Disorder with Spastic Paraplegia and...

GO Terms for Neurodevelopmental Disorder with Spastic Paraplegia and...

Sources for Neurodevelopmental Disorder with Spastic Paraplegia 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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....