NDMSBA
MCID: NRD028
MIFTS: 31

Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies (NDMSBA)

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

Aliases & Classifications for Neurodevelopmental Disorder with Progressive Microcephaly,...

MalaCards integrated aliases for Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

Name: Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies 57 72 29 6
Ndmsba 57 72
Plaa-Associated Neurodevelopmental Disorder 58
Plaand 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
some patients die in early childhood


HPO:

31
neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Developmental anomalies during embryogenesis


Summaries for Neurodevelopmental Disorder with Progressive Microcephaly,...

OMIM® : 57 NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy. Some patients die in early childhood (summary by Falik Zaccai et al., 2017 and Hall et al., 2017). (617527) (Updated 20-May-2021)

MalaCards based summary : Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies, also known as ndmsba, is related to microcephaly and spasticity. An important gene associated with Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies is PLAA (Phospholipase A2 Activating Protein). Affiliated tissues include eye and brain, and related phenotypes are intellectual disability and failure to thrive

UniProtKB/Swiss-Prot : 72 Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies: An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy.

Related Diseases for Neurodevelopmental Disorder with Progressive Microcephaly,...

Diseases related to Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 microcephaly 29.9 TRAPPC4 PLAA
2 spasticity 29.7 TRAPPC4 PLAA

Symptoms & Phenotypes for Neurodevelopmental Disorder with Progressive Microcephaly,...

Human phenotypes related to Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

58 31 (show top 50) (show all 71)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 failure to thrive 58 31 very rare (1%) Frequent (79-30%) HP:0001508
3 kyphosis 58 31 very rare (1%) Frequent (79-30%) HP:0002808
4 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
5 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
6 global developmental delay 58 31 very rare (1%) Frequent (79-30%) HP:0001263
7 delayed speech and language development 58 31 frequent (33%) Frequent (79-30%) HP:0000750
8 pectus carinatum 58 31 very rare (1%) Frequent (79-30%) HP:0000768
9 abnormal facial shape 58 31 frequent (33%) Frequent (79-30%) HP:0001999
10 short nose 58 31 frequent (33%) Frequent (79-30%) HP:0003196
11 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
12 smooth philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000319
13 optic atrophy 58 31 very rare (1%) Frequent (79-30%) HP:0000648
14 micrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000347
15 low-set, posteriorly rotated ears 58 31 frequent (33%) Frequent (79-30%) HP:0000368
16 long philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000343
17 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
18 apnea 58 31 frequent (33%) Frequent (79-30%) HP:0002104
19 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
20 tented upper lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0010804
21 postaxial hand polydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001162
22 postaxial foot polydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001830
23 hypoplasia of the corpus callosum 58 31 very rare (1%) Frequent (79-30%) HP:0002079
24 leukoencephalopathy 58 31 frequent (33%) Frequent (79-30%) HP:0002352
25 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
26 rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0002063
27 single transverse palmar crease 58 31 frequent (33%) Frequent (79-30%) HP:0000954
28 progressive spastic quadriplegia 58 31 frequent (33%) Frequent (79-30%) HP:0002478
29 rocker bottom foot 58 31 very rare (1%) Frequent (79-30%) HP:0001838
30 abnormal cortical gyration 58 31 very rare (1%) Frequent (79-30%) HP:0002536
31 hirsutism 58 31 very rare (1%) Frequent (79-30%) HP:0001007
32 impaired oropharyngeal swallow response 58 31 frequent (33%) Frequent (79-30%) HP:0031162
33 long fingers 58 31 frequent (33%) Frequent (79-30%) HP:0100807
34 hypsarrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0002521
35 cerebellar cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0008278
36 limb hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0002509
37 bulbar palsy 58 31 frequent (33%) Frequent (79-30%) HP:0001283
38 edema of the dorsum of hands 58 31 frequent (33%) Frequent (79-30%) HP:0007514
39 edema of the dorsum of feet 58 31 frequent (33%) Frequent (79-30%) HP:0012098
40 contractures of the large joints 58 31 very rare (1%) Frequent (79-30%) HP:0005781
41 delayed myelination 58 31 very rare (1%) Frequent (79-30%) HP:0012448
42 cerebral white matter atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0012762
43 exaggerated startle response 58 31 very rare (1%) Frequent (79-30%) HP:0002267
44 hyperextensibility of the finger joints 58 31 frequent (33%) Frequent (79-30%) HP:0001187
45 hypotonia 31 very rare (1%) HP:0001252
46 nystagmus 58 31 very rare (1%) Occasional (29-5%) HP:0000639
47 hyperhidrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000975
48 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
49 bulbar signs 58 31 very rare (1%) Occasional (29-5%) HP:0002483
50 seizure 31 occasional (7.5%) HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive

Skeletal Spine:
kyphosis

Neurologic Central Nervous System:
global developmental delay
rigidity
delayed myelination
exaggerated startle response
enlarged ventricles
more
Head And Neck Face:
micrognathia
long philtrum
flat philtrum

Abdomen Gastrointestinal:
feeding difficulties
poor swallowing
poor sucking

Muscle Soft Tissue:
central hypotonia
bulbar weakness
peripheral hypertonia

Skeletal:
contractures of the large joints
distal contractures
hyperextensibility of the small joints

Head And Neck Mouth:
high-arched palate
tented upper lip

Head And Neck Head:
microcephaly, progressive

Skin Nails Hair Skin:
hyperhidrosis of the palms and feet
edema of the hands and feet

Head And Neck Eyes:
nystagmus
optic atrophy (in some patients)
roving eye movements

Respiratory:
respiratory insufficiency
apnea

Head And Neck Nose:
short nose

Head And Neck Ears:
low-set ears
posteriorly rotated ears

Skin Nails Hair Hair:
hirsutism

Skeletal Hands:
long fingers
postaxial polydactyly
single palmar creases

Skeletal Feet:
postaxial polydactyly
rocker bottom feet

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum (in some patients)

Chest External Features:
chest deformities (in some patients)

Clinical features from OMIM®:

617527 (Updated 20-May-2021)

Drugs & Therapeutics for Neurodevelopmental Disorder with Progressive Microcephaly,...

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies

Genetic Tests for Neurodevelopmental Disorder with Progressive Microcephaly,...

Genetic tests related to Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

# Genetic test Affiliating Genes
1 Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies 29 PLAA

Anatomical Context for Neurodevelopmental Disorder with Progressive Microcephaly,...

MalaCards organs/tissues related to Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

40
Eye, Brain

Publications for Neurodevelopmental Disorder with Progressive Microcephaly,...

Articles related to Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

# Title Authors PMID Year
1
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies in China caused by novel mutations of PLAA. 61 57 6
31322726 2019
2
PLAA Mutations Cause a Lethal Infantile Epileptic Encephalopathy by Disrupting Ubiquitin-Mediated Endolysosomal Degradation of Synaptic Proteins. 57 6
28413018 2017
3
Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy. 57 6
28007986 2017
4
A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome. 6
32901138 2021
5
Recurrent bi-allelic splicing variant c.454+3A>G in TRAPPC4 is associated with progressive encephalopathy and muscle involvement. 6
32125366 2020
6
Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability. 6
31794024 2020

Variations for Neurodevelopmental Disorder with Progressive Microcephaly,...

ClinVar genetic disease variations for Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

6 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PLAA NM_001031689.3(PLAA):c.68G>T (p.Gly23Val) SNV Pathogenic 427941 rs747956857 GRCh37: 9:26946976-26946976
GRCh38: 9:26946978-26946978
2 PLAA NM_001031689.3(PLAA):c.68dup (p.Leu24fs) Duplication Pathogenic 427942 rs1554662408 GRCh37: 9:26946975-26946976
GRCh38: 9:26946977-26946978
3 PLAA NM_001031689.3(PLAA):c.2254C>T (p.Leu752Phe) SNV Pathogenic 427940 rs1114167457 GRCh37: 9:26905643-26905643
GRCh38: 9:26905645-26905645
4 TRAPPC4 NM_016146.6(TRAPPC4):c.454+3A>G SNV Pathogenic 812649 rs375776811 GRCh37: 11:118890966-118890966
GRCh38: 11:119020256-119020256
5 PLAA NM_001031689.3(PLAA):c.240_241insTAG (p.Pro81Ter) Insertion Pathogenic 807466 rs1587185107 GRCh37: 9:26935113-26935114
GRCh38: 9:26935115-26935116
6 PLAA NM_001031689.3(PLAA):c.120C>G (p.Asp40Glu) SNV Pathogenic 828067 rs1587205406 GRCh37: 9:26946924-26946924
GRCh38: 9:26946926-26946926
7 PLAA NM_001031689.3(PLAA):c.829T>C (p.Cys277Arg) SNV Pathogenic 975039 GRCh37: 9:26925863-26925863
GRCh38: 9:26925865-26925865
8 PLAA NM_001031689.3(PLAA):c.1049A>T (p.Glu350Val) SNV Pathogenic 975038 GRCh37: 9:26920373-26920373
GRCh38: 9:26920375-26920375
9 PLAA NM_001031689.3(PLAA):c.2350del (p.Lys783_Val784insTer) Deletion Likely pathogenic 694395 rs1587143858 GRCh37: 9:26905547-26905547
GRCh38: 9:26905549-26905549
10 PLAA NM_001031689.3(PLAA):c.2323T>C (p.Tyr775His) SNV Uncertain significance 1030979 GRCh37: 9:26905574-26905574
GRCh38: 9:26905576-26905576
11 PLAA NM_001031689.3(PLAA):c.1370G>C (p.Gly457Ala) SNV Uncertain significance 1033217 GRCh37: 9:26919355-26919355
GRCh38: 9:26919357-26919357
12 PLAA NM_001031689.3(PLAA):c.-16C>T SNV Uncertain significance 1033218 GRCh37: 9:26947059-26947059
GRCh38: 9:26947061-26947061
13 PLAA NM_001031689.3(PLAA):c.911C>G (p.Thr304Arg) SNV Uncertain significance 1033219 GRCh37: 9:26923304-26923304
GRCh38: 9:26923306-26923306
14 PLAA NM_001031689.3(PLAA):c.2264A>G (p.Asp755Gly) SNV Uncertain significance 973095 GRCh37: 9:26905633-26905633
GRCh38: 9:26905635-26905635

UniProtKB/Swiss-Prot genetic disease variations for Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies:

72
# Symbol AA change Variation ID SNP ID
1 PLAA p.Gly23Val VAR_079276 rs747956857
2 PLAA p.Leu752Phe VAR_079277 rs111416745

Expression for Neurodevelopmental Disorder with Progressive Microcephaly,...

Search GEO for disease gene expression data for Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies.

Pathways for Neurodevelopmental Disorder with Progressive Microcephaly,...

GO Terms for Neurodevelopmental Disorder with Progressive Microcephaly,...

Cellular components related to Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 8.96 TRAPPC4 PLAA
2 synapse GO:0045202 8.62 TRAPPC4 PLAA

Sources for Neurodevelopmental Disorder with Progressive Microcephaly,...

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
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44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
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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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