NMIHBA
MCID: NRD026
MIFTS: 28

Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies (NMIHBA)

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

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

MalaCards integrated aliases for Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies:

Name: Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies 57 72 6
Nmihba 57 72
Prune1-Related Neurological Syndrome 58

Characteristics:

OMIM®:

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

Miscellaneous:
progressive disorder
onset at birth


HPO:

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


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


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

OMIM® : 57 NMIHBA is a severe, autosomal recessive, neurodevelopmental, and neurodegenerative disorder characterized by global developmental delay apparent from infancy and profound intellectual disability. Affected individuals have microcephaly with accompanying dysmorphic features, truncal hypotonia, peripheral spasticity, and lack of independent ambulation or speech acquisition. Brain imaging shows variable abnormalities, including cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and delayed myelination (summary by Zollo et al., 2017). (617481) (Updated 20-May-2021)

MalaCards based summary : Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies, also known as nmihba, is related to microcephaly and alacrima, achalasia, and mental retardation syndrome. An important gene associated with Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies is PRUNE1 (Prune Exopolyphosphatase 1). Affiliated tissues include brain and skeletal muscle, and related phenotypes are cataract and narrow palate

UniProtKB/Swiss-Prot : 72 Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies: An autosomal recessive neurodevelopmental and degenerative disorder characterized by primary microcephaly, profound global developmental delay, and severe intellectual disability. Additional clinical features include dysmorphic features, truncal hypotonia, peripheral spasticity, and lack of independent ambulation or speech acquisition. Brain imaging shows cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and delayed myelination.

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

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

# Related Disease Score Top Affiliating Genes
1 microcephaly 29.1 PRUNE1 DYNC1I2
2 alacrima, achalasia, and mental retardation syndrome 9.9
3 cerebellar hypoplasia 9.9
4 hypotonia 9.9

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

Human phenotypes related to Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies:

31 (show all 23)
# Description HPO Frequency HPO Source Accession
1 cataract 31 very rare (1%) HP:0000518
2 narrow palate 31 very rare (1%) HP:0000189
3 optic atrophy 31 very rare (1%) HP:0000648
4 seizure 31 very rare (1%) HP:0001250
5 clonus 31 HP:0002169
6 scoliosis 31 HP:0002650
7 macrotia 31 HP:0000400
8 microcephaly 31 HP:0000252
9 skeletal muscle atrophy 31 HP:0003202
10 talipes equinovarus 31 HP:0001762
11 cerebral cortical atrophy 31 HP:0002120
12 protruding ear 31 HP:0000411
13 proptosis 31 HP:0000520
14 decreased fetal movement 31 HP:0001558
15 profound global developmental delay 31 HP:0012736
16 plagiocephaly 31 HP:0001357
17 sloping forehead 31 HP:0000340
18 hypoplasia of the corpus callosum 31 HP:0002079
19 cerebellar atrophy 31 HP:0001272
20 spastic tetraparesis 31 HP:0001285
21 generalized hypotonia 31 HP:0001290
22 progressive flexion contractures 31 HP:0005876
23 delayed myelination 31 HP:0012448

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
hyperreflexia
clonus
cerebellar atrophy
delayed myelination
seizures (in some patients)
more
Skeletal Feet:
talipes equinovarus

Skeletal Skull:
plagiocephaly

Muscle Soft Tissue:
hypotonia
muscle atrophy

Head And Neck Eyes:
optic atrophy (in some patients)
prominent eyes
cataracts (in some patients)

Prenatal Manifestations Movement:
decreased fetal movements

Skeletal Spine:
scoliosis

Head And Neck Head:
plagiocephaly
microcephaly (up to -6.0)

Head And Neck Face:
sloping forehead

Head And Neck Ears:
large ears
prominent ears

Skeletal:
joint contractures, progressive

Head And Neck Mouth:
narrow palate (in some patients)

Clinical features from OMIM®:

617481 (Updated 20-May-2021)

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

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies

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

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

MalaCards organs/tissues related to Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies:

40
Brain, Skeletal Muscle

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

Articles related to Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies:

# Title Authors PMID Year
1
PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. 57 6
28334956 2017
2
Homozygous mutation in PRUNE1 in an Oji-Cree male with a complex neurological phenotype. 6 57
28211990 2017
3
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. 57 6
26539891 2015
4
Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features. 6
31079899 2019
5
NMIHBA results from hypomorphic PRUNE1 variants that lack short-chain exopolyphosphatase activity. 61
33105479 2021
6
PRUNE1-related disorder: Expanding the clinical spectrum. 61
29797509 2018
7
PRUNE Syndrome Is a New Neurodevelopmental Disorder: Report and Review. 61
29372174 2018

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

ClinVar genetic disease variations for Neurodevelopmental Disorder with Microcephaly, Hypotonia, and Variable Brain Anomalies:

6 (show all 19)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PRUNE1 NM_021222.3(PRUNE1):c.316G>A (p.Asp106Asn) SNV Pathogenic 402131 rs773618224 GRCh37: 1:150991126-150991126
GRCh38: 1:151018650-151018650
2 PRUNE1 NM_021222.3(PRUNE1):c.521-2A>G SNV Pathogenic 265536 rs886039608 GRCh37: 1:150997989-150997989
GRCh38: 1:151025513-151025513
3 PRUNE1 NM_021222.3(PRUNE1):c.520G>T (p.Gly174Ter) SNV Pathogenic 402132 rs200618384 GRCh37: 1:150997271-150997271
GRCh38: 1:151024795-151024795
4 PRUNE1 NM_021222.3(PRUNE1):c.160C>A (p.Pro54Thr) SNV Pathogenic 427231 rs1085308033 GRCh37: 1:150990970-150990970
GRCh38: 1:151018494-151018494
5 PRUNE1 NM_021222.3(PRUNE1):c.383G>A (p.Arg128Gln) SNV Pathogenic 384335 rs767769359 GRCh37: 1:150997134-150997134
GRCh38: 1:151024658-151024658
6 PRUNE1 NM_021222.3(PRUNE1):c.889C>T (p.Arg297Trp) SNV Pathogenic 427232 rs752599948 GRCh37: 1:151001376-151001376
GRCh38: 1:151028900-151028900
7 PRUNE1 NM_021222.3(PRUNE1):c.132+2T>C SNV Pathogenic 932732 GRCh37: 1:150990382-150990382
GRCh38: 1:151017906-151017906
8 DYNC1I2 NM_001378.3(DYNC1I2):c.740A>G (p.Tyr247Cys) SNV Pathogenic 635400 rs752940799 GRCh37: 2:172582561-172582561
GRCh38: 2:171726051-171726051
9 DYNC1I2 NM_001378.3(DYNC1I2):c.868C>T (p.Gln290Ter) SNV Pathogenic 635401 rs1574596084 GRCh37: 2:172582801-172582801
GRCh38: 2:171726291-171726291
10 overlap with 2 genes GRCh37/hg19 1q21.3(chr1:150990288-151016203) copy number loss Pathogenic 813322 GRCh37: 1:150990288-151016203
GRCh38:
11 PRUNE1 NM_021222.3(PRUNE1):c.491del (p.Leu164fs) Deletion Pathogenic 1032876 GRCh37: 1:150997241-150997241
GRCh38: 1:151024765-151024765
12 PRUNE1 NM_021222.3(PRUNE1):c.88G>A (p.Asp30Asn) SNV Likely pathogenic 384334 rs1057521927 GRCh37: 1:150990336-150990336
GRCh38: 1:151017860-151017860
13 PRUNE1 NM_021222.3(PRUNE1):c.901A>G (p.Ile301Val) SNV Uncertain significance 592125 rs1558088029 GRCh37: 1:151001388-151001388
GRCh38: 1:151028912-151028912
14 PRUNE1 NM_021222.3(PRUNE1):c.506C>T (p.Ala169Val) SNV Uncertain significance 1032877 GRCh37: 1:150997257-150997257
GRCh38: 1:151024781-151024781
15 PRUNE1 NM_021222.3(PRUNE1):c.115G>C (p.Ala39Pro) SNV Uncertain significance 813906 rs756008936 GRCh37: 1:150990363-150990363
GRCh38: 1:151017887-151017887
16 PRUNE1 NM_021222.3(PRUNE1):c.933G>A (p.Thr311=) SNV Uncertain significance 978029 GRCh37: 1:151001420-151001420
GRCh38: 1:151028944-151028944
17 PRUNE1 NM_021222.3(PRUNE1):c.436G>T (p.Gly146Trp) SNV Uncertain significance 1029811 GRCh37: 1:150997187-150997187
GRCh38: 1:151024711-151024711
18 PRUNE1 NM_021222.3(PRUNE1):c.56A>G (p.His19Arg) SNV Uncertain significance 1029812 GRCh37: 1:150990304-150990304
GRCh38: 1:151017828-151017828
19 PRUNE1 NM_021222.3(PRUNE1):c.315C>T (p.Val105=) SNV Uncertain significance 1030370 GRCh37: 1:150991125-150991125
GRCh38: 1:151018649-151018649

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

72
# Symbol AA change Variation ID SNP ID
1 PRUNE1 p.Asp30Asn VAR_078986 rs105752192
2 PRUNE1 p.Asp106Asn VAR_078988 rs773618224
3 PRUNE1 p.Arg128Gln VAR_078989 rs767769359
4 PRUNE1 p.Arg297Trp VAR_078991 rs752599948

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

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

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

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

Sources for Neurodevelopmental Disorder with Microcephaly, Hypotonia, 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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