NEDHIB
MCID: NRD080
MIFTS: 23

Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities (NEDHIB)

Categories: Eye diseases, Genetic diseases, Neuronal diseases

Aliases & Classifications for Neurodevelopmental Disorder with Hypotonia and Variable...

MalaCards integrated aliases for Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities:

Name: Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities 57 73 6 17
Nedhib 57 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
de novo mutation
highly variable severity


HPO:

31
neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities:
Inheritance autosomal dominant germline de novo mutation


Classifications:



Summaries for Neurodevelopmental Disorder with Hypotonia and Variable...

OMIM® : 57 Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB) is characterized by early-onset hypotonia, delayed walking, poor speech, and impaired intellectual development. Additional features may include feeding difficulties, dysmorphic features, and visual defects. Brain imaging tends to show delayed myelination, thin corpus callosum, and/or enlarged ventricles. The severity of the disorder is highly variable; initial evidence suggests that the severity may depend on the type of mutation (summary by Haijes et al., 2019). (618603) (Updated 05-Mar-2021)

MalaCards based summary : Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities, is also known as nedhib. An important gene associated with Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities is POLR2A (RNA Polymerase II Subunit A). Affiliated tissues include brain, skeletal muscle and globus pallidus, and related phenotypes are agenesis of corpus callosum and failure to thrive

UniProtKB/Swiss-Prot : 73 Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities: An autosomal dominant neurodevelopmental disorder characterized by profound infantile-onset hypotonia, developmental delay with poor speech, delayed walking, and impaired intellectual development. Additional variable features include feeding difficulties, dysmorphic features, and visual defects.

Related Diseases for Neurodevelopmental Disorder with Hypotonia and Variable...

Symptoms & Phenotypes for Neurodevelopmental Disorder with Hypotonia and Variable...

Human phenotypes related to Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities:

31 (show all 33)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 31 very rare (1%) HP:0001274
2 failure to thrive 31 very rare (1%) HP:0001508
3 sleep disturbance 31 very rare (1%) HP:0002360
4 high palate 31 very rare (1%) HP:0000218
5 inguinal hernia 31 very rare (1%) HP:0000023
6 hypertelorism 31 very rare (1%) HP:0000316
7 recurrent respiratory infections 31 very rare (1%) HP:0002205
8 microcephaly 31 very rare (1%) HP:0000252
9 visual impairment 31 very rare (1%) HP:0000505
10 gastroesophageal reflux 31 very rare (1%) HP:0002020
11 brachycephaly 31 very rare (1%) HP:0000248
12 skeletal muscle atrophy 31 very rare (1%) HP:0003202
13 strabismus 31 very rare (1%) HP:0000486
14 developmental stagnation 31 very rare (1%) HP:0007281
15 cleft palate 31 very rare (1%) HP:0000175
16 pectus excavatum 31 very rare (1%) HP:0000767
17 ventriculomegaly 31 very rare (1%) HP:0002119
18 high forehead 31 very rare (1%) HP:0000348
19 decreased fetal movement 31 very rare (1%) HP:0001558
20 plagiocephaly 31 very rare (1%) HP:0001357
21 misalignment of teeth 31 very rare (1%) HP:0000692
22 hypoplasia of the corpus callosum 31 very rare (1%) HP:0002079
23 feeding difficulties 31 very rare (1%) HP:0011968
24 autistic behavior 31 very rare (1%) HP:0000729
25 generalized hypotonia 31 very rare (1%) HP:0001290
26 enlarged cisterna magna 31 very rare (1%) HP:0002280
27 exercise intolerance 31 very rare (1%) HP:0003546
28 delayed cns myelination 31 very rare (1%) HP:0002188
29 abnormal globus pallidus morphology 31 very rare (1%) HP:0002453
30 frog-leg posture 31 very rare (1%) HP:0031139
31 seizure 31 very rare (1%) HP:0001250
32 delayed ability to sit 31 HP:0025336
33 delayed ability to walk 31 HP:0031936

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Growth Other:
failure to thrive

Neurologic Central Nervous System:
global developmental delay
inability to walk
sleep disturbances
enlarged ventricles
speech delay
more
Head And Neck Eyes:
hypertelorism
strabismus
impaired visual development

Head And Neck Head:
microcephaly

Chest External Features:
pectus excavatum

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
tapering fingers

Head And Neck Teeth:
misaligned teeth

Abdomen Gastrointestinal:
dysphagia
gastroesophageal reflux
feeding difficulties
tube feeding

Muscle Soft Tissue:
inguinal hernia
hypotonia
muscle atrophy
decreased endurance

Respiratory:
recurrent respiratory infections

Skeletal Skull:
brachycephaly
plagiocephaly

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior
short attention span
abnormal behavior
autistic features
poor social interaction

Skeletal:
hyperextensible joints

Prenatal Manifestations Movement:
decreased fetal movements

Head And Neck Face:
dysmorphic features, variable (in some patients)

Clinical features from OMIM®:

618603 (Updated 05-Mar-2021)

Drugs & Therapeutics for Neurodevelopmental Disorder with Hypotonia and Variable...

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities

Genetic Tests for Neurodevelopmental Disorder with Hypotonia and Variable...

Anatomical Context for Neurodevelopmental Disorder with Hypotonia and Variable...

MalaCards organs/tissues related to Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities:

40
Brain, Skeletal Muscle, Globus Pallidus

Publications for Neurodevelopmental Disorder with Hypotonia and Variable...

Articles related to Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities:

# Title Authors PMID Year
1
De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome with Profound Infantile-Onset Hypotonia. 6 57
31353023 2019

Variations for Neurodevelopmental Disorder with Hypotonia and Variable...

ClinVar genetic disease variations for Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities:

6 (show all 17)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 POLR2A NM_000937.5(POLR2A):c.1370T>C (p.Ile457Thr) SNV Pathogenic 691497 rs1597796823 17:7402392-7402392 17:7499073-7499073
2 POLR2A NM_000937.5(POLR2A):c.2098C>T (p.Gln700Ter) SNV Pathogenic 691498 rs1597798340 17:7404655-7404655 17:7501336-7501336
3 POLR2A NM_000937.5(POLR2A):c.2203C>T (p.Gln735Ter) SNV Pathogenic 691499 rs1597798503 17:7404902-7404902 17:7501583-7501583
4 POLR2A NM_000937.5(POLR2A):c.2207C>T (p.Thr736Met) SNV Pathogenic 691500 rs1597798507 17:7404906-7404906 17:7501587-7501587
5 POLR2A NM_000937.5(POLR2A):c.3371T>C (p.Leu1124Pro) SNV Pathogenic 691501 rs1597803125 17:7411700-7411700 17:7508381-7508381
6 POLR2A NM_000937.5(POLR2A):c.3752A>G (p.Asn1251Ser) SNV Pathogenic 873138 17:7412890-7412890 17:7509571-7509571
7 POLR2A NM_000937.5(POLR2A):c.4252G>A (p.Gly1418Arg) SNV Pathogenic 873139 17:7415280-7415280 17:7511961-7511961
8 POLR2A NM_000937.5(POLR2A):c.5438_5439CA[1] (p.Gln1814fs) Microsatellite Likely pathogenic 873140 17:7417021-7417022 17:7513702-7513703
9 POLR2A NM_000937.5(POLR2A):c.83C>G (p.Pro28Arg) SNV Likely pathogenic 873141 17:7388166-7388166 17:7484847-7484847
10 POLR2A NM_000937.5(POLR2A):c.323G>A (p.Arg108His) SNV Likely pathogenic 873142 17:7399625-7399625 17:7496306-7496306
11 POLR2A NM_000937.5(POLR2A):c.418C>T (p.Arg140Trp) SNV Likely pathogenic 873143 17:7399813-7399813 17:7496494-7496494
12 POLR2A NM_000937.5(POLR2A):c.3275C>T (p.Ala1092Val) SNV Likely pathogenic 873144 17:7411604-7411604 17:7508285-7508285
13 POLR2A NM_000937.5(POLR2A):c.5428C>T (p.Arg1810Ter) SNV Likely pathogenic 982794 17:7417011-7417011 17:7513692-7513692
14 POLR2A NM_000937.5(POLR2A):c.2508C>A (p.Phe836Leu) SNV Likely pathogenic 983018 17:7405377-7405377 17:7502058-7502058
15 POLR2A NM_000937.5(POLR2A):c.1314_1319del (p.His439_Leu440del) Deletion Likely pathogenic 873135 17:7401504-7401509 17:7498185-7498190
16 POLR2A NM_000937.5(POLR2A):c.3281C>T (p.Ser1094Phe) SNV Likely pathogenic 873136 17:7411610-7411610 17:7508291-7508291
17 POLR2A NM_000937.5(POLR2A):c.3407C>T (p.Thr1136Ile) SNV Likely pathogenic 873137 17:7411736-7411736 17:7508417-7508417

UniProtKB/Swiss-Prot genetic disease variations for Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities:

73
# Symbol AA change Variation ID SNP ID
1 POLR2A p.Thr736Met VAR_082994
2 POLR2A p.Leu1124Pro VAR_082999

Expression for Neurodevelopmental Disorder with Hypotonia and Variable...

Search GEO for disease gene expression data for Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities.

Pathways for Neurodevelopmental Disorder with Hypotonia and Variable...

GO Terms for Neurodevelopmental Disorder with Hypotonia and Variable...

Sources for Neurodevelopmental Disorder with Hypotonia and Variable...

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....