CDCBM1
MCID: CRT070
MIFTS: 41

Cortical Dysplasia, Complex, with Other Brain Malformations 1 (CDCBM1)

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

Aliases & Classifications for Cortical Dysplasia, Complex, with Other Brain Malformations 1

MalaCards integrated aliases for Cortical Dysplasia, Complex, with Other Brain Malformations 1:

Name: Cortical Dysplasia, Complex, with Other Brain Malformations 1 56 52 73 29 6 71
Cortical Dysgenesis with Pontocerebellar Hypoplasia Due to Tubb3 Mutation 12 52 58
Cdcbm1 56 12 73
Complex Cortical Dysplasia with Other Brain Malformations 1 12 15
Malformations of Cortical Development, Group Ii 43

Characteristics:

Orphanet epidemiological data:

58
cortical dysgenesis with pontocerebellar hypoplasia due to tubb3 mutation
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth
highly variable severity


HPO:

31
cortical dysplasia, complex, with other brain malformations 1:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Cortical Dysplasia, Complex, with Other Brain Malformations 1

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 300570 Definition A rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disease characterized by the association of cortical dysplasia and pontocerebellar hypoplasia, manifesting with global developmental delay , mild to severe intellectual disability , axial hypotonia , strabismus , nystagmus and, occasionally, optic nerve hypoplasia. Brain imaging reveals variable malformations, including frontally predominant microgyria, gyral disorganization and simplification, dysmorphic and hypertrophic basal ganglia, cerebellar vermis dysplasia, brainstem/corpus callosum hypoplasia, and/or olfactory bulbs agenesis. Visit the Orphanet disease page for more resources.

MalaCards based summary : Cortical Dysplasia, Complex, with Other Brain Malformations 1, also known as cortical dysgenesis with pontocerebellar hypoplasia due to tubb3 mutation, is related to neuronal migration disorders and cortical dysplasia, complex, with other brain malformations 7, and has symptoms including muscle spasticity An important gene associated with Cortical Dysplasia, Complex, with Other Brain Malformations 1 is TUBB3 (Tubulin Beta 3 Class III), and among its related pathways/superpathways are Pathogenic Escherichia coli infection and Regulation of CFTR activity (norm and CF). Affiliated tissues include brain, olfactory bulb and eye, and related phenotypes are intellectual disability and feeding difficulties in infancy

Disease Ontology : 12 A complex cortical dysplasia with other brain malformations that has material basis in autosomal dominant inheritance of heterozygous mutation in the tubulin beta 3 class III (TUBB3) gene on chromosome 16q24.3.

OMIM : 56 Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved (summary by Poirier et al., 2010). Mutation in the TUBB3 gene can also cause congenital fibrosis of extraocular muscles-3A (CFEOM3A; 600638), a milder and somewhat different neurologic phenotype. (614039)

UniProtKB/Swiss-Prot : 73 Cortical dysplasia, complex, with other brain malformations 1: A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved.

Related Diseases for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Graphical network of the top 20 diseases related to Cortical Dysplasia, Complex, with Other Brain Malformations 1:



Diseases related to Cortical Dysplasia, Complex, with Other Brain Malformations 1

Symptoms & Phenotypes for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Human phenotypes related to Cortical Dysplasia, Complex, with Other Brain Malformations 1:

58 31 (show top 50) (show all 87)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 feeding difficulties in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0008872
3 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
4 postnatal growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0008897
5 severe global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0011344
6 polymicrogyria 58 31 frequent (33%) Frequent (79-30%) HP:0002126
7 cerebellar hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0001321
8 partial agenesis of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0001338
9 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
10 expressive language delay 58 31 frequent (33%) Frequent (79-30%) HP:0002474
11 inability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0002540
12 spastic ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002497
13 poor speech 58 31 frequent (33%) Frequent (79-30%) HP:0002465
14 esotropia 58 31 frequent (33%) Frequent (79-30%) HP:0000565
15 type ii lissencephaly 58 31 frequent (33%) Frequent (79-30%) HP:0007260
16 hypoplasia of the brainstem 58 31 frequent (33%) Frequent (79-30%) HP:0002365
17 infantile axial hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0009062
18 bilateral ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0001488
19 delayed fine motor development 58 31 frequent (33%) Frequent (79-30%) HP:0010862
20 delayed ability to sit 58 31 frequent (33%) Frequent (79-30%) HP:0025336
21 simplified gyral pattern 31 frequent (33%) HP:0009879
22 macrocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000256
23 stereotypy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000733
24 spastic tetraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002510
25 genu valgum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002857
26 metatarsus adductus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001840
27 cubitus valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0002967
28 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
29 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
30 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
31 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
32 delayed social development 58 31 occasional (7.5%) Occasional (29-5%) HP:0012434
33 joint laxity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001388
34 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
35 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
36 dysarthria 58 31 occasional (7.5%) Occasional (29-5%) HP:0001260
37 flat occiput 58 31 occasional (7.5%) Occasional (29-5%) HP:0005469
38 insomnia 58 31 occasional (7.5%) Occasional (29-5%) HP:0100785
39 small hand 58 31 occasional (7.5%) Occasional (29-5%) HP:0200055
40 plagiocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001357
41 short foot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001773
42 torticollis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000473
43 cerebellar vermis hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001320
44 spastic diplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001264
45 oculomotor apraxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000657
46 visual loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0000572
47 impaired mastication 58 31 occasional (7.5%) Occasional (29-5%) HP:0005216
48 short attention span 58 31 occasional (7.5%) Occasional (29-5%) HP:0000736
49 optic nerve hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000609
50 bilateral sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0008619

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
lissencephaly
agenesis of the corpus callosum
delayed psychomotor development
mental retardation, mild to severe
more
Head And Neck Head:
microcephaly (in some patients)

Head And Neck Eyes:
nystagmus
strabismus

Clinical features from OMIM:

614039

UMLS symptoms related to Cortical Dysplasia, Complex, with Other Brain Malformations 1:


muscle spasticity

Drugs & Therapeutics for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Human Epilepsy Genetics--Neuronal Migration Disorders Study Unknown status NCT00041600

Search NIH Clinical Center for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Cochrane evidence based reviews: malformations of cortical development, group ii

Genetic Tests for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Genetic tests related to Cortical Dysplasia, Complex, with Other Brain Malformations 1:

# Genetic test Affiliating Genes
1 Cortical Dysplasia, Complex, with Other Brain Malformations 1 29 TUBB3

Anatomical Context for Cortical Dysplasia, Complex, with Other Brain Malformations 1

MalaCards organs/tissues related to Cortical Dysplasia, Complex, with Other Brain Malformations 1:

40
Brain, Olfactory Bulb, Eye, Testes, Thalamus

Publications for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Articles related to Cortical Dysplasia, Complex, with Other Brain Malformations 1:

# Title Authors PMID Year
1
Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly. 56 6
25059107 2014
2
Mutations in the neuronal ß-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects. 56 6
20829227 2010
3
Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. 6
20074521 2010

Variations for Cortical Dysplasia, Complex, with Other Brain Malformations 1

ClinVar genetic disease variations for Cortical Dysplasia, Complex, with Other Brain Malformations 1:

6 (show all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TUBB3 NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys)SNV Pathogenic 6967 rs267607165 16:90002087-90002087 16:89935679-89935679
2 TUBB3 NM_006086.4(TUBB3):c.967A>G (p.Met323Val)SNV Pathogenic 30272 rs878853256 16:90001826-90001826 16:89935418-89935418
3 TUBB3 NM_006086.4(TUBB3):c.613G>A (p.Glu205Lys)SNV Pathogenic 30274 rs878853257 16:90001472-90001472 16:89935064-89935064
4 TUBB3 NM_006086.4(TUBB3):c.905C>T (p.Ala302Val)SNV Pathogenic 30275 rs878853258 16:90001764-90001764 16:89935356-89935356
5 TUBB3 NM_006086.4(TUBB3):c.1162A>G (p.Met388Val)SNV Pathogenic 236243 rs878853279 16:90002021-90002021 16:89935613-89935613
6 TUBB3 NM_006086.4(TUBB3):c.136C>T (p.Arg46Trp)SNV Likely pathogenic 438582 rs1555625363 16:89999057-89999057 16:89932649-89932649
7 TUBB3 NM_006086.4(TUBB3):c.982G>A (p.Glu328Lys)SNV Likely pathogenic 374309 rs1057518686 16:90001841-90001841 16:89935433-89935433
8 TUBB3 NM_006086.4(TUBB3):c.862G>A (p.Glu288Lys)SNV Likely pathogenic 384329 rs1057521924 16:90001721-90001721 16:89935313-89935313
9 TUBB3 NM_006086.4(TUBB3):c.533C>T (p.Thr178Met)SNV Conflicting interpretations of pathogenicity 265335 rs747480526 16:90001392-90001392 16:89934984-89934984
10 TUBB3 NM_006086.4(TUBB3):c.292G>A (p.Gly98Ser)SNV Conflicting interpretations of pathogenicity 160191 rs587784505 16:90001151-90001151 16:89934743-89934743
11 TUBB3 NM_006086.4(TUBB3):c.728C>T (p.Pro243Leu)SNV Uncertain significance 160195 rs587784506 16:90001587-90001587 16:89935179-89935179
12 TUBB3 NM_006086.4(TUBB3):c.740A>G (p.Asn247Ser)SNV Uncertain significance 160196 rs587784507 16:90001599-90001599 16:89935191-89935191
13 TUBB3 NM_006086.4(TUBB3):c.993G>A (p.Leu331=)SNV Uncertain significance 160197 rs61743716 16:90001852-90001852 16:89935444-89935444
14 TUBB3 NM_006086.4(TUBB3):c.1170G>A (p.Arg390=)SNV Uncertain significance 160188 rs587784503 16:90002029-90002029 16:89935621-89935621
15 TUBB3 NM_006086.4(TUBB3):c.167-6C>TSNV Uncertain significance 160190 rs144873806 16:89999870-89999870 16:89933462-89933462
16 TUBB3 NM_006086.4(TUBB3):c.1200C>T (p.Gly400=)SNV Uncertain significance 267734 rs144689076 16:90002059-90002059 16:89935651-89935651
17 TUBB2B NM_178012.5(TUBB2B):c.1105G>T (p.Gly369Cys)SNV Uncertain significance 638432 6:3225218-3225218 6:3224984-3224984

UniProtKB/Swiss-Prot genetic disease variations for Cortical Dysplasia, Complex, with Other Brain Malformations 1:

73
# Symbol AA change Variation ID SNP ID
1 TUBB3 p.Thr178Met VAR_066206 rs747480526
2 TUBB3 p.Glu205Lys VAR_066207 rs878853257
3 TUBB3 p.Ala302Val VAR_066208 rs878853258
4 TUBB3 p.Met323Val VAR_066209 rs878853256

Expression for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Search GEO for disease gene expression data for Cortical Dysplasia, Complex, with Other Brain Malformations 1.

Pathways for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Pathways related to Cortical Dysplasia, Complex, with Other Brain Malformations 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.74 TUBB3 TUBB2B
2
Show member pathways
11.65 TUBB3 TUBB2B
3 11.55 TUBB3 TUBB2B
4 11.51 TUBB3 TUBB2B
5
Show member pathways
11.48 TUBB3 TUBB2B
6
Show member pathways
11.34 TUBB3 TUBB2B
7
Show member pathways
11.19 TUBB3 TUBB2B
8 10.93 TUBB3 TUBB2B
9 10.57 TUBB3 TUBB2B

GO Terms for Cortical Dysplasia, Complex, with Other Brain Malformations 1

Biological processes related to Cortical Dysplasia, Complex, with Other Brain Malformations 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton organization GO:0007010 9.26 TUBB3 TUBB2B
2 mitotic cell cycle GO:0000278 9.16 TUBB3 TUBB2B
3 microtubule cytoskeleton organization GO:0000226 8.96 TUBB3 TUBB2B
4 microtubule-based process GO:0007017 8.62 TUBB3 TUBB2B

Molecular functions related to Cortical Dysplasia, Complex, with Other Brain Malformations 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural constituent of cytoskeleton GO:0005200 8.62 TUBB3 TUBB2B

Sources for Cortical Dysplasia, Complex, with Other Brain Malformations 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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30 HMDB
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32 ICD10
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43 MeSH
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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