CDCBM1
MCID: CRT070
MIFTS: 32

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 57 53 74 29 6 72
Cortical Dysgenesis with Pontocerebellar Hypoplasia Due to Tubb3 Mutation 12 53 59
Cdcbm1 57 12 74
Complex Cortical Dysplasia with Other Brain Malformations 1 12
Malformations of Cortical Development, Group Ii 44

Characteristics:

Orphanet epidemiological data:

59
cortical dysgenesis with pontocerebellar hypoplasia due to tubb3 mutation
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth
highly variable severity


HPO:

32
cortical dysplasia, complex, with other brain malformations 1:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0090137
MeSH 44 D054081
ICD10 33 Q04.3
ICD10 via Orphanet 34 Q04.3
Orphanet 59 ORPHA300570
UMLS 72 C3808397

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

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 300570DefinitionA 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 autosomal dominant inheritance of heterozygous mutation in the tubulin beta 3 class III (TUBB3) gene on chromosome 16q24.3.

OMIM : 57 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 : 74 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

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

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

59 32 (show top 50) (show all 86)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
2 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
3 feeding difficulties in infancy 59 32 frequent (33%) Frequent (79-30%) HP:0008872
4 severe global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0011344
5 postnatal growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0008897
6 inability to walk 59 32 frequent (33%) Frequent (79-30%) HP:0002540
7 cerebellar hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0001321
8 polymicrogyria 59 32 frequent (33%) Frequent (79-30%) HP:0002126
9 partial agenesis of the corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0001338
10 hypoplasia of the corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0002079
11 expressive language delay 59 32 frequent (33%) Frequent (79-30%) HP:0002474
12 esotropia 59 32 frequent (33%) Frequent (79-30%) HP:0000565
13 poor speech 59 32 frequent (33%) Frequent (79-30%) HP:0002465
14 spastic ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0002497
15 bilateral ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0001488
16 infantile axial hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0009062
17 delayed fine motor development 59 32 frequent (33%) Frequent (79-30%) HP:0010862
18 type ii lissencephaly 59 32 frequent (33%) Frequent (79-30%) HP:0007260
19 hypoplasia of the brainstem 59 32 frequent (33%) Frequent (79-30%) HP:0002365
20 delayed ability to sit 59 32 frequent (33%) Frequent (79-30%) HP:0025336
21 simplified gyral pattern 32 frequent (33%) HP:0009879
22 macrocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000256
23 low-set ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0000369
24 genu valgum 59 32 occasional (7.5%) Occasional (29-5%) HP:0002857
25 high palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000218
26 seizures 59 32 occasional (7.5%) Obligate (100%) HP:0001250
27 dysarthria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001260
28 stereotypy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000733
29 spastic tetraplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002510
30 micrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000347
31 epicanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000286
32 short foot 59 32 occasional (7.5%) Occasional (29-5%) HP:0001773
33 metatarsus adductus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001840
34 cubitus valgus 59 32 occasional (7.5%) Occasional (29-5%) HP:0002967
35 delayed social development 59 32 occasional (7.5%) Occasional (29-5%) HP:0012434
36 joint laxity 59 32 occasional (7.5%) Occasional (29-5%) HP:0001388
37 kyphoscoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002751
38 optic nerve hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000609
39 small hand 59 32 occasional (7.5%) Occasional (29-5%) HP:0200055
40 impaired social interactions 59 32 occasional (7.5%) Occasional (29-5%) HP:0000735
41 visual loss 59 32 occasional (7.5%) Occasional (29-5%) HP:0000572
42 downslanted palpebral fissures 59 32 occasional (7.5%) Occasional (29-5%) HP:0000494
43 flat occiput 59 32 occasional (7.5%) Occasional (29-5%) HP:0005469
44 insomnia 59 32 occasional (7.5%) Occasional (29-5%) HP:0100785
45 plagiocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001357
46 impaired mastication 59 32 occasional (7.5%) Occasional (29-5%) HP:0005216
47 torticollis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000473
48 oculomotor apraxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000657
49 spastic diplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001264
50 cerebellar vermis hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001320

Symptoms via clinical synopsis from OMIM:

57
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

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:

41
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. 8 71
25059107 2014
2
Mutations in the neuronal ß-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects. 8 71
20829227 2010
3
Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. 71
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 16)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TUBB3 NM_001197181.2(TUBB3): c.1012G> A (p.Glu338Lys) single nucleotide variant Pathogenic rs267607165 16:90002087-90002087 16:89935679-89935679
2 TUBB3 NM_001197181.2(TUBB3): c.751A> G (p.Met251Val) single nucleotide variant Pathogenic rs878853256 16:90001826-90001826 16:89935418-89935418
3 TUBB3 NM_001197181.2(TUBB3): c.397G> A (p.Glu133Lys) single nucleotide variant Pathogenic rs878853257 16:90001472-90001472 16:89935064-89935064
4 TUBB3 NM_001197181.2(TUBB3): c.689C> T (p.Ala230Val) single nucleotide variant Pathogenic rs878853258 16:90001764-90001764 16:89935356-89935356
5 TUBB3 NM_001197181.2(TUBB3): c.946A> G (p.Met316Val) single nucleotide variant Pathogenic rs878853279 16:90002021-90002021 16:89935613-89935613
6 TUBB3 NM_001197181.2(TUBB3): c.766G> A (p.Glu256Lys) single nucleotide variant Likely pathogenic rs1057518686 16:90001841-90001841 16:89935433-89935433
7 TUBB3 NM_001197181.2(TUBB3): c.-81C> T single nucleotide variant Likely pathogenic rs1555625363 16:89999057-89999057 16:89932649-89932649
8 TUBB3 NM_001197181.2(TUBB3): c.317C> T (p.Thr106Met) single nucleotide variant Conflicting interpretations of pathogenicity rs747480526 16:90001392-90001392 16:89934984-89934984
9 TUBB3 NM_001197181.2(TUBB3): c.76G> A (p.Gly26Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587784505 16:90001151-90001151 16:89934743-89934743
10 TUBB3 NM_001197181.2(TUBB3): c.512C> T (p.Pro171Leu) single nucleotide variant Uncertain significance rs587784506 16:90001587-90001587 16:89935179-89935179
11 TUBB3 NM_001197181.2(TUBB3): c.524A> G (p.Asn175Ser) single nucleotide variant Uncertain significance rs587784507 16:90001599-90001599 16:89935191-89935191
12 TUBB3 NM_001197181.2(TUBB3): c.777G> A (p.Leu259=) single nucleotide variant Uncertain significance rs61743716 16:90001852-90001852 16:89935444-89935444
13 TUBB3 NM_001197181.2(TUBB3): c.954G> A (p.Arg318=) single nucleotide variant Uncertain significance rs587784503 16:90002029-90002029 16:89935621-89935621
14 TUBB3 NM_001197181.2(TUBB3): c.-50-6C> T single nucleotide variant Uncertain significance rs144873806 16:89999870-89999870 16:89933462-89933462
15 TUBB3 NM_001197181.2(TUBB3): c.984C> T (p.Gly328=) single nucleotide variant Uncertain significance rs144689076 16:90002059-90002059 16:89935651-89935651
16 TUBB2B NM_178012.5(TUBB2B): c.1105G> T (p.Gly369Cys) single nucleotide variant Uncertain significance 6:3225218-3225218 6:3224984-3224984

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

74
# 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

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

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

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