CDCBM1
MCID: CRT070
MIFTS: 31

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

Categories: 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 58 54 76 30 6 74
Cortical Dysgenesis with Pontocerebellar Hypoplasia Due to Tubb3 Mutation 12 54 60
Cdcbm1 58 12 76
Complex Cortical Dysplasia with Other Brain Malformations 1 12
Malformations of Cortical Development, Group Ii 45

Characteristics:

Orphanet epidemiological data:

60
cortical dysgenesis with pontocerebellar hypoplasia due to tubb3 mutation
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth
highly variable severity


HPO:

33
cortical dysplasia, complex, with other brain malformations 1:
Onset and clinical course variable expressivity congenital onset
Inheritance autosomal dominant inheritance


Classifications:



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

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 300570Disease definitionA 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). Affiliated tissues include brain, olfactory bulb and eye, and related phenotypes are nystagmus and intellectual disability

Disease Ontology : 12 A complex cortical dysplasia with other brain malformations that has material basis in heterozygous mutation in the TUBB3 gene on chromosome 16q24.3.

OMIM : 58 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 : 76 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

Diseases related to Cortical Dysplasia, Complex, with Other Brain Malformations 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 neuronal migration disorders 11.6
2 cortical dysplasia, complex, with other brain malformations 7 11.1
3 cortical dysplasia, complex, with other brain malformations 9 11.1

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

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

60 33 (show top 50) (show all 87)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
2 intellectual disability 60 33 frequent (33%) Frequent (79-30%) HP:0001249
3 feeding difficulties in infancy 60 33 frequent (33%) Frequent (79-30%) HP:0008872
4 severe global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0011344
5 postnatal growth retardation 60 33 frequent (33%) Frequent (79-30%) HP:0008897
6 inability to walk 60 33 frequent (33%) Frequent (79-30%) HP:0002540
7 cerebellar hypoplasia 60 33 frequent (33%) Frequent (79-30%) HP:0001321
8 partial agenesis of the corpus callosum 60 33 frequent (33%) Frequent (79-30%) HP:0001338
9 polymicrogyria 60 33 frequent (33%) Frequent (79-30%) HP:0002126
10 hypoplasia of the corpus callosum 60 33 frequent (33%) Frequent (79-30%) HP:0002079
11 expressive language delay 60 33 frequent (33%) Frequent (79-30%) HP:0002474
12 esotropia 60 33 frequent (33%) Frequent (79-30%) HP:0000565
13 spastic ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002497
14 bilateral ptosis 60 33 frequent (33%) Frequent (79-30%) HP:0001488
15 poor speech 60 33 frequent (33%) Frequent (79-30%) HP:0002465
16 delayed fine motor development 60 33 frequent (33%) Frequent (79-30%) HP:0010862
17 infantile axial hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0009062
18 type ii lissencephaly 60 33 frequent (33%) Frequent (79-30%) HP:0007260
19 hypoplasia of the brainstem 60 33 frequent (33%) Frequent (79-30%) HP:0002365
20 delayed ability to sit 60 33 frequent (33%) Frequent (79-30%) HP:0025336
21 simplified gyral pattern 33 frequent (33%) HP:0009879
22 macrocephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000256
23 low-set ears 60 33 occasional (7.5%) Occasional (29-5%) HP:0000369
24 genu valgum 60 33 occasional (7.5%) Occasional (29-5%) HP:0002857
25 high palate 60 33 occasional (7.5%) Occasional (29-5%) HP:0000218
26 seizures 60 33 occasional (7.5%) Obligate (100%) HP:0001250
27 dysarthria 60 33 occasional (7.5%) Occasional (29-5%) HP:0001260
28 stereotypy 60 33 occasional (7.5%) Occasional (29-5%) HP:0000733
29 spastic tetraplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002510
30 micrognathia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000347
31 epicanthus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000286
32 short foot 60 33 occasional (7.5%) Occasional (29-5%) HP:0001773
33 metatarsus adductus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001840
34 cubitus valgus 60 33 occasional (7.5%) Occasional (29-5%) HP:0002967
35 delayed social development 60 33 occasional (7.5%) Occasional (29-5%) HP:0012434
36 joint laxity 60 33 occasional (7.5%) Occasional (29-5%) HP:0001388
37 kyphoscoliosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002751
38 optic nerve hypoplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000609
39 small hand 60 33 occasional (7.5%) Occasional (29-5%) HP:0200055
40 impaired social interactions 60 33 occasional (7.5%) Occasional (29-5%) HP:0000735
41 visual loss 60 33 occasional (7.5%) Occasional (29-5%) HP:0000572
42 downslanted palpebral fissures 60 33 occasional (7.5%) Occasional (29-5%) HP:0000494
43 flat occiput 60 33 occasional (7.5%) Occasional (29-5%) HP:0005469
44 insomnia 60 33 occasional (7.5%) Occasional (29-5%) HP:0100785
45 plagiocephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0001357
46 torticollis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000473
47 oculomotor apraxia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000657
48 spastic diplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001264
49 cerebellar vermis hypoplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001320
50 thoracic scoliosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002943

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
strabismus

Head And Neck Head:
microcephaly (in some patients)

Neurologic Central Nervous System:
spasticity
lissencephaly
agenesis of the corpus callosum
delayed psychomotor development
mental retardation, mild to severe
more

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

Search Clinical Trials , 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 30 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:

42
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 Year
1
Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly. ( 25059107 )
2014
2
Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. ( 20074521 )
2010
3
Mutations in the neuronal ß-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects. ( 20829227 )
2010

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

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

76
# 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

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

6 (show all 30)
# Gene Variation Type Significance SNP ID Assembly Location
1 TUBB3 NM_006086.3(TUBB3): c.1228G> A (p.Glu410Lys) single nucleotide variant Pathogenic rs267607165 GRCh37 Chromosome 16, 90002087: 90002087
2 TUBB3 NM_006086.3(TUBB3): c.1228G> A (p.Glu410Lys) single nucleotide variant Pathogenic rs267607165 GRCh38 Chromosome 16, 89935679: 89935679
3 TUBB3 NM_001197181.1(TUBB3): c.751A> G (p.Met251Val) single nucleotide variant Pathogenic rs878853256 GRCh38 Chromosome 16, 89935418: 89935418
4 TUBB3 NM_001197181.1(TUBB3): c.751A> G (p.Met251Val) single nucleotide variant Pathogenic rs878853256 GRCh37 Chromosome 16, 90001826: 90001826
5 TUBB3 NM_006086.3(TUBB3): c.613G> A (p.Glu205Lys) single nucleotide variant Pathogenic rs878853257 GRCh37 Chromosome 16, 90001472: 90001472
6 TUBB3 NM_006086.3(TUBB3): c.613G> A (p.Glu205Lys) single nucleotide variant Pathogenic rs878853257 GRCh38 Chromosome 16, 89935064: 89935064
7 TUBB3 NM_001197181.1(TUBB3): c.689C> T (p.Ala230Val) single nucleotide variant Pathogenic rs878853258 GRCh37 Chromosome 16, 90001764: 90001764
8 TUBB3 NM_001197181.1(TUBB3): c.689C> T (p.Ala230Val) single nucleotide variant Pathogenic rs878853258 GRCh38 Chromosome 16, 89935356: 89935356
9 TUBB3 NM_006086.3(TUBB3): c.167-6C> T single nucleotide variant Uncertain significance rs144873806 GRCh37 Chromosome 16, 89999870: 89999870
10 TUBB3 NM_006086.3(TUBB3): c.167-6C> T single nucleotide variant Uncertain significance rs144873806 GRCh38 Chromosome 16, 89933462: 89933462
11 TUBB3 NM_006086.3(TUBB3): c.292G> A (p.Gly98Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587784505 GRCh37 Chromosome 16, 90001151: 90001151
12 TUBB3 NM_006086.3(TUBB3): c.292G> A (p.Gly98Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587784505 GRCh38 Chromosome 16, 89934743: 89934743
13 TUBB3 NM_006086.3(TUBB3): c.728C> T (p.Pro243Leu) single nucleotide variant Uncertain significance rs587784506 GRCh37 Chromosome 16, 90001587: 90001587
14 TUBB3 NM_006086.3(TUBB3): c.728C> T (p.Pro243Leu) single nucleotide variant Uncertain significance rs587784506 GRCh38 Chromosome 16, 89935179: 89935179
15 TUBB3 NM_006086.3(TUBB3): c.740A> G (p.Asn247Ser) single nucleotide variant Uncertain significance rs587784507 GRCh37 Chromosome 16, 90001599: 90001599
16 TUBB3 NM_006086.3(TUBB3): c.740A> G (p.Asn247Ser) single nucleotide variant Uncertain significance rs587784507 GRCh38 Chromosome 16, 89935191: 89935191
17 TUBB3 NM_006086.3(TUBB3): c.993G> A (p.Leu331=) single nucleotide variant Uncertain significance rs61743716 GRCh37 Chromosome 16, 90001852: 90001852
18 TUBB3 NM_006086.3(TUBB3): c.993G> A (p.Leu331=) single nucleotide variant Uncertain significance rs61743716 GRCh38 Chromosome 16, 89935444: 89935444
19 TUBB3 NM_006086.3(TUBB3): c.1170G> A (p.Arg390=) single nucleotide variant Uncertain significance rs587784503 GRCh37 Chromosome 16, 90002029: 90002029
20 TUBB3 NM_006086.3(TUBB3): c.1170G> A (p.Arg390=) single nucleotide variant Uncertain significance rs587784503 GRCh38 Chromosome 16, 89935621: 89935621
21 TUBB3 NM_001197181.1(TUBB3): c.946A> G (p.Met316Val) single nucleotide variant Pathogenic rs878853279 GRCh37 Chromosome 16, 90002021: 90002021
22 TUBB3 NM_001197181.1(TUBB3): c.946A> G (p.Met316Val) single nucleotide variant Pathogenic rs878853279 GRCh38 Chromosome 16, 89935613: 89935613
23 TUBB3 NM_006086.3(TUBB3): c.533C> T (p.Thr178Met) single nucleotide variant Conflicting interpretations of pathogenicity rs747480526 GRCh37 Chromosome 16, 90001392: 90001392
24 TUBB3 NM_006086.3(TUBB3): c.533C> T (p.Thr178Met) single nucleotide variant Conflicting interpretations of pathogenicity rs747480526 GRCh38 Chromosome 16, 89934984: 89934984
25 TUBB3 NM_006086.3(TUBB3): c.1200C> T (p.Gly400=) single nucleotide variant Uncertain significance rs144689076 GRCh38 Chromosome 16, 89935651: 89935651
26 TUBB3 NM_006086.3(TUBB3): c.1200C> T (p.Gly400=) single nucleotide variant Uncertain significance rs144689076 GRCh37 Chromosome 16, 90002059: 90002059
27 TUBB3 NM_006086.3(TUBB3): c.982G> A (p.Glu328Lys) single nucleotide variant Likely pathogenic rs1057518686 GRCh38 Chromosome 16, 89935433: 89935433
28 TUBB3 NM_006086.3(TUBB3): c.982G> A (p.Glu328Lys) single nucleotide variant Likely pathogenic rs1057518686 GRCh37 Chromosome 16, 90001841: 90001841
29 TUBB3 NM_006086.3(TUBB3): c.136C> T (p.Arg46Trp) single nucleotide variant Likely pathogenic rs1555625363 GRCh37 Chromosome 16, 89999057: 89999057
30 TUBB3 NM_006086.3(TUBB3): c.136C> T (p.Arg46Trp) single nucleotide variant Likely pathogenic rs1555625363 GRCh38 Chromosome 16, 89932649: 89932649

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

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

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....