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Complex cortical dysplasia with other brain malformations 7(PMGYSA; CDCBM7)

MedGen UID:
765150
Concept ID:
C3552236
Disease or Syndrome
Synonym: Polymicrogyria, asymmetric
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): TUBB2B (6p25.2)
 
Monarch Initiative: MONDO:0012399
OMIM®: 610031
Orphanet: ORPHA300573

Definition

Complex cortical dysplasia with other brain malformations-7 is an autosomal dominant, clinically heterogeneous disorder showing a wide spectrum of abnormalities of cortical brain development. The most severely affected patients are fetuses with microlissencephaly, absence of the cortical plate, agenesis of the corpus callosum, and severely hypoplastic brainstem and cerebellum. Other patients have lissencephaly, polymicrogyria, cortical dysplasia, or neuronal heterotopia. Those with less severe malformations can survive, but usually have some degree of neurologic impairment, such as mental retardation, seizures, and movement abnormalities (summary by Chang et al., 2006; Fallet-Bianco et al., 2014). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039). [from OMIM]

Additional description

From MedlinePlus Genetics
Bilateral forms of polymicrogyria tend to cause more severe neurological problems. Signs and symptoms of these conditions can include recurrent seizures (epilepsy), delayed development, crossed eyes, problems with speech and swallowing, and muscle weakness or paralysis. The most severe form of the disorder, bilateral generalized polymicrogyria, affects the entire brain. This condition causes severe intellectual disability, problems with movement, and seizures that are difficult or impossible to control with medication.

Polymicrogyria most often occurs as an isolated feature, although it can occur with other brain abnormalities. It is also a feature of several genetic syndromes characterized by intellectual disability and multiple birth defects. These include 22q11.2 deletion syndrome, Adams-Oliver syndrome, Aicardi syndrome, Galloway-Mowat syndrome, Joubert syndrome, and Zellweger spectrum disorder.

Researchers have identified multiple forms of polymicrogyria. The mildest form is known as unilateral focal polymicrogyria. This form of the condition affects a relatively small area on one side of the brain. It may cause minor neurological problems, such as mild seizures that can be easily controlled with medication. Some people with unilateral focal polymicrogyria do not have any problems associated with the condition.

Polymicrogyria can affect part of the brain or the whole brain. When the condition affects one side of the brain, researchers describe it as unilateral. When it affects both sides of the brain, it is described as bilateral. The signs and symptoms associated with polymicrogyria depend on how much of the brain, and which particular brain regions, are affected.

Polymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. The name of this condition literally means too many (poly-) small (micro-) folds (-gyria) in the surface of the brain.  https://medlineplus.gov/genetics/condition/polymicrogyria

Clinical features

From HPO
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
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.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
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.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Macrogyria
MedGen UID:
120579
Concept ID:
C0266483
Congenital Abnormality
Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
Tetraparesis
MedGen UID:
78731
Concept ID:
C0270790
Finding
Weakness of all four limbs.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Partial agenesis of the corpus callosum
MedGen UID:
98127
Concept ID:
C0431368
Congenital Abnormality
A partial failure of the development of the corpus callosum.
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.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Frontoparietal cortical dysplasia
MedGen UID:
870512
Concept ID:
C4024959
Congenital Abnormality
The presence of developmental dysplasia of the cortex of frontal lobe and the cortex of parietal lobe.
Unilateral polymicrogyria
MedGen UID:
870513
Concept ID:
C4024960
Disease or Syndrome
Excessive number of small gyri (convolutions) on the surface of one side of the brain.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Congenital fibrosis of extraocular muscles
MedGen UID:
724506
Concept ID:
C1302995
Disease or Syndrome
Congenital fibrosis of the extraocular muscles (CFEOM) is a disorder of the nervous system that affects use of the muscles that surround the eyes (extraocular muscles). These muscles control eye movement and the direction of the eyes (for example, looking straight ahead). CFEOM impairs control of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, most people with CFEOM have droopy eyelids (ptosis), which further limits their vision.\n\nResearchers have identified several forms of CFEOM, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome (sometimes called CFEOM4). The specific problems with eye movement vary among the types, and some types are associated with additional signs and symptoms. People with CFEOM1 and CFEOM2 have only the eye problems described above. In CFEOM1, the eyes typically point downward, whereas in CFEOM2, the eyes usually turn outward.\n\nCFEOM3 can include additional neurological problems, such as intellectual disability; difficulty with social skills; a smaller-than-normal head size (microcephaly); muscle weakness in the face; nonfunctioning vocal cords; and a set of symptoms called Kallmann syndrome, which features delayed or absent puberty and an impaired sense of smell. Some affected individuals develop pain, weakness, or a decreased ability to feel sensations in the limbs (peripheral neuropathy), which can begin in childhood or adulthood.\n\nBrain abnormalities can also occur in people with CFEOM3. Some have abnormal development of the white matter, which is brain tissue containing nerve cell fibers (axons) that transmit nerve impulses. A particular form of CFEOM3, known as CFEOM3 with polymicrogyria, is characterized by abnormal development of the brain, in which the folds and ridges on the surface of the brain are smaller and more numerous than usual.\n\nTukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement.
Limited extraocular movements
MedGen UID:
388060
Concept ID:
C1858427
Finding
Limited mobility of the eye within its socket.
Abnormality of the eye
MedGen UID:
1370071
Concept ID:
C4316870
Anatomical Abnormality
Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVComplex cortical dysplasia with other brain malformations 7

Professional guidelines

PubMed

Bąbol-Pokora K, Bielska M, Bobeff K, Jatczak-Pawlik I, Borkowska J, Kotulska K, Jóźwiak S, Młynarski W, Trelińska J
Eur J Med Genet 2021 Oct;64(10):104309. Epub 2021 Aug 14 doi: 10.1016/j.ejmg.2021.104309. PMID: 34403804
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
Guerreiro MM, Andermann F, Andermann E, Palmini A, Hwang P, Hoffman HJ, Otsubo H, Bastos A, Dubeau F, Snipes GJ, Olivier A, Rasmussen T
Neurology 1998 Nov;51(5):1263-9. doi: 10.1212/wnl.51.5.1263. PMID: 9818843

Recent clinical studies

Etiology

Aronica E, Specchio N, Luinenburg MJ, Curatolo P
Brain 2023 Jul 3;146(7):2694-2710. doi: 10.1093/brain/awad048. PMID: 36806388Free PMC Article
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
Zöllner JP, Grau J, Rosenow F, Sauter M, Knuf M, Kurlemann G, Mayer T, Hertzberg C, Bertsche A, Immisch I, Klein KM, Knake S, Marquard K, Meyer S, Noda AH, von Podewils F, Schäfer H, Thiels C, Willems LM, Zukunft B, Schubert-Bast S, Strzelczyk A
Orphanet J Rare Dis 2021 Jun 2;16(1):250. doi: 10.1186/s13023-021-01838-w. PMID: 34078440Free 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
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

Diagnosis

Licchetta L, Bruschi G, Stipa C, Belotti LMB, Ferri L, Mostacci B, Vignatelli L, Minardi R, Di Vito L, Muccioli L, Boni A, Tinuper P, Bisulli F
Epilepsy Behav 2024 Apr;153:109688. Epub 2024 Feb 29 doi: 10.1016/j.yebeh.2024.109688. PMID: 38428171
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
Hulshof HM, Brenner J, Overwater IE, Wit MC, Braun KPJ, Jansen FE
Eur J Paediatr Neurol 2020 Mar;25:113-119. Epub 2020 Jan 7 doi: 10.1016/j.ejpn.2020.01.004. PMID: 31982306
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
Cossu M, Fuschillo D, Casaceli G, Pelliccia V, Castana L, Mai R, Francione S, Sartori I, Gozzo F, Nobili L, Tassi L, Cardinale F, Lo Russo G
J Neurosurg 2015 Dec;123(6):1358-67. Epub 2015 Jun 19 doi: 10.3171/2014.12.JNS141968. PMID: 26090841

Therapy

Licchetta L, Bruschi G, Stipa C, Belotti LMB, Ferri L, Mostacci B, Vignatelli L, Minardi R, Di Vito L, Muccioli L, Boni A, Tinuper P, Bisulli F
Epilepsy Behav 2024 Apr;153:109688. Epub 2024 Feb 29 doi: 10.1016/j.yebeh.2024.109688. PMID: 38428171
Aronica E, Specchio N, Luinenburg MJ, Curatolo P
Brain 2023 Jul 3;146(7):2694-2710. doi: 10.1093/brain/awad048. PMID: 36806388Free PMC Article
Zöllner JP, Grau J, Rosenow F, Sauter M, Knuf M, Kurlemann G, Mayer T, Hertzberg C, Bertsche A, Immisch I, Klein KM, Knake S, Marquard K, Meyer S, Noda AH, von Podewils F, Schäfer H, Thiels C, Willems LM, Zukunft B, Schubert-Bast S, Strzelczyk A
Orphanet J Rare Dis 2021 Jun 2;16(1):250. doi: 10.1186/s13023-021-01838-w. PMID: 34078440Free 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
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

Prognosis

Licchetta L, Bruschi G, Stipa C, Belotti LMB, Ferri L, Mostacci B, Vignatelli L, Minardi R, Di Vito L, Muccioli L, Boni A, Tinuper P, Bisulli F
Epilepsy Behav 2024 Apr;153:109688. Epub 2024 Feb 29 doi: 10.1016/j.yebeh.2024.109688. PMID: 38428171
Aronica E, Specchio N, Luinenburg MJ, Curatolo P
Brain 2023 Jul 3;146(7):2694-2710. doi: 10.1093/brain/awad048. PMID: 36806388Free 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
Hulshof HM, Brenner J, Overwater IE, Wit MC, Braun KPJ, Jansen FE
Eur J Paediatr Neurol 2020 Mar;25:113-119. Epub 2020 Jan 7 doi: 10.1016/j.ejpn.2020.01.004. PMID: 31982306
Fohlen M, Ferrand-Sorbets S, Delalande O, Dorfmüller G
Childs Nerv Syst 2018 Aug;34(8):1511-1519. Epub 2018 May 15 doi: 10.1007/s00381-018-3826-6. PMID: 29766265

Clinical prediction guides

Licchetta L, Bruschi G, Stipa C, Belotti LMB, Ferri L, Mostacci B, Vignatelli L, Minardi R, Di Vito L, Muccioli L, Boni A, Tinuper P, Bisulli F
Epilepsy Behav 2024 Apr;153:109688. Epub 2024 Feb 29 doi: 10.1016/j.yebeh.2024.109688. PMID: 38428171
Rosengren T, Nanhoe S, de Almeida LGD, Schönewolf-Greulich B, Larsen LJ, Hey CAB, Dunø M, Ek J, Risom L, Nellist M, Møller LB
Sci Rep 2020 Jun 18;10(1):9909. doi: 10.1038/s41598-020-66588-4. PMID: 32555378Free PMC Article
Manara R, Brotto D, Bugin S, Pelizza MF, Sartori S, Nosadini M, Azzolini S, Iaconetta G, Parazzini C, Murgia A, Peron A, Canevini P, Labriola F, Vignoli A, Toldo I
Neuroradiology 2018 Aug;60(8):813-820. Epub 2018 Jun 17 doi: 10.1007/s00234-018-2045-x. PMID: 29909560
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
Cossu M, Fuschillo D, Casaceli G, Pelliccia V, Castana L, Mai R, Francione S, Sartori I, Gozzo F, Nobili L, Tassi L, Cardinale F, Lo Russo G
J Neurosurg 2015 Dec;123(6):1358-67. Epub 2015 Jun 19 doi: 10.3171/2014.12.JNS141968. PMID: 26090841

Recent systematic reviews

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

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