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Cortical dysplasia, complex, with other brain malformations 12(CDCBM12)

MedGen UID:
1841043
Concept ID:
C5830407
Disease or Syndrome
Synonym: CDCBM12
 
Gene (location): CAMSAP1 (9q34.3)
 
Monarch Initiative: MONDO:0957217
OMIM®: 620316

Definition

Complex cortical dysplasia with other brain malformations-12 (CDCBM12) is an autosomal recessive disorder of developmental neuronal migration characterized by severe to profound neurodevelopmental delay with absent speech, central hypotonia, peripheral spasticity, cortical visual impairment, and dysmorphic craniofacial features. Affected individuals usually have feeding difficulties and show minimal developmental progress of motor or cognitive skills. Most have microcephaly and develop early-onset refractory seizures. Brain imaging shows cortical abnormalities, such as lissencephaly and pachygyria, as well as other brain malformations, including thin or absent corpus callosum, dysplastic basal ganglia, and mild cerebellar hypoplasia. Due to the function of CAMSAP1 in microtubule stability and maintenance, this disorder can be classified as a 'tubulinopathy' (Khalaf-Nazzal et al., 2022). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
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.
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.
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.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
EEG with burst suppression
MedGen UID:
369943
Concept ID:
C1969156
Finding
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
Dysgenesis of the basal ganglia
MedGen UID:
1370512
Concept ID:
C4476592
Congenital Abnormality
Structural abnormality of the basal ganglia related to defective development.
Pachygyria
MedGen UID:
504794
Concept ID:
CN001193
Finding
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.
Femoral hernia
MedGen UID:
9231
Concept ID:
C0019288
Finding
A hernia which occurs just below the inguinal ligament, where abdominal contents pass through a naturally occurring weakness called the femoral canal.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Enlarged posterior fossa
MedGen UID:
340998
Concept ID:
C1855889
Finding
Abnormal increased size of the posterior cranial fossa.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Exaggerated cupid bow
MedGen UID:
376842
Concept ID:
C1850629
Finding
More pronounced paramedian peaks and median notch of the Cupid's bow.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Professional guidelines

PubMed

Shen YW, Wang YY, Zhang MN, Xu Y, Lu Q, He W, Chen HM, Liu LY, Pang LY, Wang QH, Dun S, Li YF, Gao J, Han F, Zou LP
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Samuels JA
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Recent clinical studies

Etiology

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
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Tian X, Glass JE, Kwiatkowski DJ, Towbin AJ, Li Y, Sund KL, Krueger DA, Franz DN, McCormack FX, Gupta N
Ann Am Thorac Soc 2021 May;18(5):815-819. doi: 10.1513/AnnalsATS.202008-911OC. PMID: 33171065
Overwater IE, Rietman AB, Mous SE, Bindels-de Heus K, Rizopoulos D, Ten Hoopen LW, van der Vaart T, Jansen FE, Elgersma Y, Moll HA, de Wit MY; ENCORE Expertise Centre for Neurodevelopmental Disorders
Neurology 2019 Jul 9;93(2):e200-e209. Epub 2019 Jun 19 doi: 10.1212/WNL.0000000000007749. PMID: 31217257
Sahin M, Henske EP, Manning BD, Ess KC, Bissler JJ, Klann E, Kwiatkowski DJ, Roberds SL, Silva AJ, Hillaire-Clarke CS, Young LR, Zervas M, Mamounas LA; Tuberous Sclerosis Complex Working Group to Update the Research Plan
Pediatr Neurol 2016 Jul;60:1-12. Epub 2016 Apr 2 doi: 10.1016/j.pediatrneurol.2016.03.015. PMID: 27267556Free PMC Article
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Diagnosis

d'Orio P, Pelliccia V, Biondi D, Scarpa P, Gozzo F, Revay M, Cardinale F, Tassi L, Cossu M
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Fahmy MD, Gupta A, Padilla RJ, Segura A, Brookes CD
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JAMA Neurol 2013 Dec;70(12):1491-8. doi: 10.1001/jamaneurol.2013.4598. PMID: 24126608Free PMC Article

Therapy

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PLoS One 2022;17(5):e0268597. Epub 2022 May 19 doi: 10.1371/journal.pone.0268597. PMID: 35587487Free PMC Article
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Orphanet J Rare Dis 2021 Jun 2;16(1):250. doi: 10.1186/s13023-021-01838-w. PMID: 34078440Free PMC Article
Overwater IE, Rietman AB, Mous SE, Bindels-de Heus K, Rizopoulos D, Ten Hoopen LW, van der Vaart T, Jansen FE, Elgersma Y, Moll HA, de Wit MY; ENCORE Expertise Centre for Neurodevelopmental Disorders
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Prognosis

d'Orio P, Pelliccia V, Biondi D, Scarpa P, Gozzo F, Revay M, Cardinale F, Tassi L, Cossu M
Seizure 2022 Apr;97:8-14. Epub 2022 Feb 27 doi: 10.1016/j.seizure.2022.02.013. PMID: 35247673
Willems LM, Schubert-Bast S, Grau J, Hertzberg C, Kurlemann G, Wiemer-Kruel A, Bast T, Bertsche A, Bettendorf U, Fiedler B, Hahn A, Hartmann H, Hornemann F, Immisch I, Jacobs J, Kieslich M, Klein KM, Klotz KA, Kluger G, Knuf M, Mayer T, Marquard K, Meyer S, Muhle H, Müller-Schlüter K, Noda AH, Ruf S, Sauter M, Schlump JU, Syrbe S, Thiels C, Trollmann R, Wilken B, Zöllner JP, Rosenow F, Strzelczyk A
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Hsieh DT, Jennesson MM, Thiele EA
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Clinical prediction guides

Levine A, Davis P, Zhang B, Peters J, Filip-Dhima R, Warfield SK, Prohl A, Capal J, Krueger D, Bebin EM, Northrup H, Wu JY, Sahin M; TACERN Study Group
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Seizure 2022 Apr;97:8-14. Epub 2022 Feb 27 doi: 10.1016/j.seizure.2022.02.013. PMID: 35247673
Willems LM, Schubert-Bast S, Grau J, Hertzberg C, Kurlemann G, Wiemer-Kruel A, Bast T, Bertsche A, Bettendorf U, Fiedler B, Hahn A, Hartmann H, Hornemann F, Immisch I, Jacobs J, Kieslich M, Klein KM, Klotz KA, Kluger G, Knuf M, Mayer T, Marquard K, Meyer S, Muhle H, Müller-Schlüter K, Noda AH, Ruf S, Sauter M, Schlump JU, Syrbe S, Thiels C, Trollmann R, Wilken B, Zöllner JP, Rosenow F, Strzelczyk A
Eur J Paediatr Neurol 2021 Nov;35:111-122. Epub 2021 Oct 7 doi: 10.1016/j.ejpn.2021.10.003. PMID: 34673401
Mailleux L, Klingels K, Fiori S, Simon-Martinez C, Demaerel P, Locus M, Fosseprez E, Boyd RN, Guzzetta A, Ortibus E, Feys H
Eur J Paediatr Neurol 2017 Sep;21(5):763-772. Epub 2017 May 29 doi: 10.1016/j.ejpn.2017.05.006. PMID: 28606752
Jissendi-Tchofo P, Kara S, Barkovich AJ
Neurology 2009 Feb 3;72(5):410-8. Epub 2008 Nov 19 doi: 10.1212/01.wnl.0000333256.74903.94. PMID: 19020296Free PMC Article

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