U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Complex cortical dysplasia with other brain malformations 1(CDCBM1)

MedGen UID:
814727
Concept ID:
C3808397
Disease or Syndrome
Synonyms: CDCBM1; CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 1
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): TUBB3 (16q24.3)
 
Monarch Initiative: MONDO:0013541
OMIM®: 614039
Orphanet: ORPHA300570

Definition

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). Genetic Heterogeneity of Complex Cortical Dysplasia with Other Brain Malformations See also CDCBM2 (615282), caused by mutation in the KIF5C gene (604593) on chromosome 2q23; CDCBM3 (615411), caused by mutation in the KIF2A gene (602591) on chromosome 5q12; CDCBM4 (615412), caused by mutation in the TUBG1 gene (191135) on chromosome 17q21; CDCBM5 (615763), caused by mutation in the TUBB2A gene (615101) on chromosome 6p25; CDCBM6 (615771), caused by mutation in the TUBB gene (191130) on chromosome 6p21; CDCBM7 (610031), caused by mutation in the TUBB2B gene (612850) on chromosome 6p25; CDCBM9 (618174), caused by mutation in the CTNNA2 gene (114025) on chromosome 2p12; CDCBM10 (618677), caused by mutation in the APC2 gene (612034) on chromosome 19p13; CDCBM11 (620156), caused by mutation in the KIF26A gene (613231) on chromosome 14q32; CDCBM12 (620316), caused by mutation in the CAMSAP1 gene (613774) on chromosome 9q34; CDCBM13 (614563), caused by mutation in the DYNC1H1 gene (600112) on chromosome 14q32; CDCBM14A (606854) and CDCBM14B (615752), caused by mutation in the ADGRG1 gene (604110) on chromosome 16q21; and CDCBM15 (618737), caused by mutation in the TUBGCP2 gene (617817) on chromosome 10q26. The designation CDCBM8 was previously used to represent a phenotype caused by mutation in the TUBA8 gene (see 605742.0001) on chromosome 22q11; the patients with this phenotype were subsequently found to have a homozygous mutation in the SNAP29 gene (604202.0002), also on chromosome 22q11, that may have been responsible for the disorder. The same mutation in SNAP29 causes a similar disorder, CEDNIK syndrome (609528). See also lissencephaly (e.g., LIS1, 607432), which shows overlapping features and may result from mutation in tubulin genes. [from OMIM]

Clinical features

From HPO
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Lissencephaly
MedGen UID:
78604
Concept ID:
C0266463
Finding
A spectrum of malformations of cortical development caused by insufficient neuronal migration that subsumes the terms agyria, pachygyria and subcortical band heterotopia. See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Cortical dysplasia
MedGen UID:
98129
Concept ID:
C0431380
Congenital Abnormality
The presence of developmental dysplasia of the cerebral cortex.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Frontal polymicrogyria
MedGen UID:
335671
Concept ID:
C1847356
Finding
A type of polymicrogyria with a gradient of severity (anterior more severe than posterior) extending from frontal poles posteriorly to precentral gyrus and inferiorly to frontal operculum.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Fusion of the caudate and putamen
MedGen UID:
1814343
Concept ID:
C5676774
Anatomical Abnormality
Abnormal joined appearance of the caudate and putamen with an absence of the anterior limb of the internal capsule.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVComplex cortical dysplasia with other brain malformations 1

Professional guidelines

PubMed

Togi S, Ura H, Hatanaka H, Niida Y
Int J Mol Sci 2022 Sep 22;23(19) doi: 10.3390/ijms231911175. PMID: 36232477Free PMC Article
van der Poest Clement E, Jansen FE, Braun KPJ, Peters JM
Paediatr Drugs 2020 Feb;22(1):73-84. doi: 10.1007/s40272-019-00376-0. PMID: 31912454
Samuels JA
Clin J Am Soc Nephrol 2017 Jul 7;12(7):1196-1202. Epub 2017 Mar 16 doi: 10.2215/CJN.08150816. PMID: 28302901Free PMC Article

Recent clinical studies

Etiology

Capitanio JF, Mortini P
Adv Exp Med Biol 2023;1405:645-672. doi: 10.1007/978-3-031-23705-8_25. PMID: 37452957
Calì E, Lin SJ, Rocca C, Sahin Y, Al Shamsi A, El Chehadeh S, Chaabouni M, Mankad K, Galanaki E, Efthymiou S, Sudhakar S, Athanasiou-Fragkouli A, Çelik T, Narlı N, Bianca S, Murphy D, De Carvalho Moreira FM; SYNaPS Study Group, Andrea Accogli, Petree C, Huang K, Monastiri K, Edizadeh M, Nardello R, Ognibene M, De Marco P, Ruggieri M, Zara F, Striano P, Şahin Y, Al-Gazali L, Abi Warde MT, Gerard B, Zifarelli G, Beetz C, Fortuna S, Soler M, Valente EM, Varshney G, Maroofian R, Salpietro V, Houlden H
Genet Med 2022 Oct;24(10):2194-2203. Epub 2022 Aug 24 doi: 10.1016/j.gim.2022.07.013. PMID: 36001086Free PMC Article
Islam MP
Semin Pediatr Neurol 2021 Apr;37:100875. Epub 2021 Feb 11 doi: 10.1016/j.spen.2021.100875. PMID: 33892851
Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O'Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCARE6 Study Group
JAMA Neurol 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607. PMID: 33346789Free PMC Article
Douglas KAA, Douglas VP, Cestari DM
Curr Opin Ophthalmol 2019 Nov;30(6):434-442. doi: 10.1097/ICU.0000000000000609. PMID: 31464700

Diagnosis

Islam MP
Semin Pediatr Neurol 2021 Apr;37:100875. Epub 2021 Feb 11 doi: 10.1016/j.spen.2021.100875. PMID: 33892851
Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O'Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCARE6 Study Group
JAMA Neurol 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607. PMID: 33346789Free PMC Article
Uysal SP, Şahin M
Turk J Med Sci 2020 Nov 3;50(SI-2):1665-1676. doi: 10.3906/sag-2002-133. PMID: 32222129Free PMC Article
Douglas KAA, Douglas VP, Cestari DM
Curr Opin Ophthalmol 2019 Nov;30(6):434-442. doi: 10.1097/ICU.0000000000000609. PMID: 31464700
Islam MP, Roach ES
Handb Clin Neurol 2015;132:97-109. doi: 10.1016/B978-0-444-62702-5.00006-8. PMID: 26564073

Therapy

Leitner DF, Kanshin E, Askenazi M, Siu Y, Friedman D, Devore S, Jones D, Ueberheide B, Wisniewski T, Devinsky O
PLoS One 2022;17(5):e0268597. Epub 2022 May 19 doi: 10.1371/journal.pone.0268597. PMID: 35587487Free PMC Article
Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O'Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCARE6 Study Group
JAMA Neurol 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607. PMID: 33346789Free PMC Article
Ebrahimi-Fakhari D, Franz DN
Expert Opin Pharmacother 2020 Aug;21(11):1329-1336. Epub 2020 Apr 27 doi: 10.1080/14656566.2020.1751124. PMID: 32338549
Samuels JA
Clin J Am Soc Nephrol 2017 Jul 7;12(7):1196-1202. Epub 2017 Mar 16 doi: 10.2215/CJN.08150816. PMID: 28302901Free PMC Article
Kohrman MH
Pediatr Neurol 2012 May;46(5):267-75. doi: 10.1016/j.pediatrneurol.2012.02.015. PMID: 22520346

Prognosis

Numoto S, Kurahashi H, Sato A, Kubota M, Shiihara T, Okanishi T, Tanaka R, Kuki I, Fukuyama T, Kashiwagi M, Ikeno M, Kubota K, Akasaka M, Mimaki M, Okumura A
Orphanet J Rare Dis 2021 Jan 6;16(1):5. doi: 10.1186/s13023-020-01646-8. PMID: 33407677Free PMC Article
Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O'Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCARE6 Study Group
JAMA Neurol 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607. PMID: 33346789Free PMC Article
Walker CL, Little ME, Roby JA, Armistead B, Gale M Jr, Rajagopal L, Nelson BR, Ehinger N, Mason B, Nayeri U, Curry CL, Adams Waldorf KM
Am J Obstet Gynecol 2019 Jan;220(1):45-56. Epub 2018 Aug 29 doi: 10.1016/j.ajog.2018.08.035. PMID: 30171843Free PMC Article
Crino PB
Acta Neuropathol 2013 Mar;125(3):317-32. Epub 2013 Feb 6 doi: 10.1007/s00401-013-1085-x. PMID: 23386324
Kohrman MH
Pediatr Neurol 2012 May;46(5):267-75. doi: 10.1016/j.pediatrneurol.2012.02.015. PMID: 22520346

Clinical prediction guides

Musante L, Faletra F, Meier K, Tomoum H, Najarzadeh Torbati P, Blair E, North S, Gärtner J, Diegmann S, Beiraghi Toosi M, Ashrafzadeh F, Ghayoor Karimiani E, Murphy D, Murru FM, Zanus C, Magnolato A, La Bianca M, Feresin A, Girotto G, Gasparini P, Costa P, Carrozzi M
Am J Med Genet A 2022 Sep;188(9):2652-2665. Epub 2022 Jun 7 doi: 10.1002/ajmg.a.62852. PMID: 35670379Free PMC Article
Walker CL, Little ME, Roby JA, Armistead B, Gale M Jr, Rajagopal L, Nelson BR, Ehinger N, Mason B, Nayeri U, Curry CL, Adams Waldorf KM
Am J Obstet Gynecol 2019 Jan;220(1):45-56. Epub 2018 Aug 29 doi: 10.1016/j.ajog.2018.08.035. PMID: 30171843Free PMC Article
Steiner JE, McCoy GN, Hess CP, Dobyns WB, Metry DW, Drolet BA, Maheshwari M, Siegel DH
Am J Med Genet A 2018 Jan;176(1):48-55. Epub 2017 Nov 24 doi: 10.1002/ajmg.a.38523. PMID: 29171184Free PMC Article
Pecoraro A, Arehart E, Gallentine W, Radtke R, Smith E, Pizoli C, Kansagra S, Abdelnour E, McLendon R, Mikati MA
Epilepsy Behav 2017 Aug;73:137-141. Epub 2017 Jul 18 doi: 10.1016/j.yebeh.2017.05.011. PMID: 28633092
Habib SL
Adv Exp Med Biol 2010;685:84-94. doi: 10.1007/978-1-4419-6448-9_8. PMID: 20687497

Recent systematic reviews

Romero VI, Arias-Almeida B, Aguiar SA
BMC Genomics 2022 Dec 22;23(1):849. doi: 10.1186/s12864-022-09071-w. PMID: 36550402Free PMC Article
Sasongko TH, Ismail NF, Zabidi-Hussin Z
Cochrane Database Syst Rev 2016 Jul 13;7(7):CD011272. doi: 10.1002/14651858.CD011272.pub2. PMID: 27409709Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...