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Table of Contents
CASE REPORT
Year : 2013  |  Volume : 16  |  Issue : 3  |  Page : 422-424
 

Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome


Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, California, Keck School of Medicine of University of Southern California, USA

Date of Submission18-May-2012
Date of Decision22-Jun-2012
Date of Acceptance07-Jul-2012
Date of Web Publication26-Aug-2013

Correspondence Address:
Jay Desai
MD Children's Hospital Los Angeles, California, Keck School of Medicine of University of Southern California, 4650 Sunset Boulevard # 82, Los Angeles, California, 90027
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-2327.116924

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   Abstract 

Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi have been described with SOX2 gene mutations. A neocortical malformation is presented here in association with SOX2 deletion that over time underwent spontaneous evolution and decrease in size.


Keywords: Cortical malformation, SOX2, anophthalmia


How to cite this article:
Desai J, Rosser T. Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome. Ann Indian Acad Neurol 2013;16:422-4

How to cite this URL:
Desai J, Rosser T. Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome. Ann Indian Acad Neurol [serial online] 2013 [cited 2019 Oct 16];16:422-4. Available from: http://www.annalsofian.org/text.asp?2013/16/3/422/116924



   Case Summary Top


The patient was born at 36 weeks gestational age to a 39-year-old multigravida after a pregnancy that was complicated by gestational diabetes. There was no significant family history. The patient was noted to have bilateral anophthalmia, choanal atresia, and bilateral cryptorchidism at birth. Magnetic resonance imaging of brain was performed and detected a large mass in the right frontal and parietal lobes with a cleft extending into the center of the lesion with the adjacent sulcal pattern that was suggestive of polymicrogyria. Magnetic resonance spectroscopy showed high choline suggesting hypercellularity. Repeat magnetic resonance imaging of brain at 1 month of age did not show any change [Figure 1], [Figure 2], [Figure 3] but a third magnetic resonance imaging of brain at 7 months of age showed a decrease in the size of the mass. A magnetic resonance imaging study at 2 years and 1 month of age showed further decrease in the size of the mass [Figure 4], [Figure 5], [Figure 6]. A single nucleotide polymorphism array revealed a previously known pathogenic mutation, a deletion of approximately 1 megabase on chromosome 3q26.33 containing six reference sequence genes including SOX2 (chromosomal microarray nomenclature: Arr3q26.33q26.33 (182,127,678-183,154 ,618) × 1. The child is now 2 years old and has intractable focal epilepsy; left sided hemiparesis; and global developmental delay with inability to sit and no vocalizations other than babbling.
Figure 1: Sagittal View at 1 Month of Age

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Figure 2: Coronal View at 1 Month of Age

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Figure 3: Axial View at 1 Month of Age

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Figure 4: Sagittal View at 2 Years and 1 Month of Age

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Figure 5: Coronal View at 2 Years and 1 Month of Age

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Figure 6: Axial View at 2 Years and 1 Month of Age

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   Discussion Top


SOX2 is a member of the SOX family which consists of 20 genes in humans, each of which is defined by a sex determining region of the Y chromosome (SRY) related DNA binding domain that is highly conserved across eukaryotic species and known as the high mobility group (HMG) box. [1],[2] SOX2 is expressed during various phases of embryonic development and plays a critical role in embryogenesis. It is a key regulator of neural progenitor identity and is required for stem cell maintenance in the central nervous system. [3],[4] SOX2 gene mutations are inherited in an autosomal dominant manner but often arise de novo and are associated with anophthalmia, microphthalmia or less commonly anterior segment dysgenesis, optic nerve hypoplasia, cataract, coloboma, and retinal dysplasia. [5],[6],[7],[8],[9],[10] Other associations include dysfunction of hypothalamo-pituitary axis, male genital abnormalities including micropenis and cryptorchidism, esophageal atresia, tracheoesophageal fistula, and choanal atresia. [7],[8],[11],[12],[13] Neurologic manifestations reported in association include learning disability, delayed motor development, seizures, sensorineural hearing loss and brain malformations including agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi. [6],[7],[9],[10],[14] A single case of schizencephaly has been described with a SOX 2 missense variant that was inherited from a phenotypically normal father and not predicted to lead to loss of function. [7] No neocortical malformations have been reported as an association. This case not only expands the spectrum of the phenotype of SOX2 gene mutations but also describes an evolution in an unusual cortical malformation with a spontaneous decrease in size, for which we do not have a good explanation from our review of literature.


   Acknowledgments Top


The authors would like to thank Drs. Matt Lallas, Maria T. Toczek, Quyen Luc, and Wendy G. Mitchell for critical review of the draft and feedback; and Dr. Richard G. Boles who was the consulting Geneticist.

 
   References Top

1.Collignon J, Sockanathan S, Hacker A, Cohen-Tannoudji M, Norris D, Rastan S, et al. A comparison of the properties of SOX-3 with Sry and two related genes, SOX-1 and SOX-2. Development 1996;122:509-20.  Back to cited text no. 1
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2.Schepers GE, Teasdale RD, Koopman P. Twenty pairs of sox: Extent, homology, and nomenclature of the mouse and human sox transcription factor gene families. Dev Cell 2002;3:167-70.  Back to cited text no. 2
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3.Pevny L, Placzek M. SOX genes and neural progenitor identity. Curr Opin Neurobiol 2005;15:7-13.  Back to cited text no. 3
    
4.Wegner M, Stolt CC. From stem cells to neurons and glia: A Soxist's view of neural development. Trends Neurosci 2005;28:583-8.  Back to cited text no. 4
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5.Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, et al. Mutations in SOX2 cause anophthalmia. Nat Genet 2003;33:461-3.  Back to cited text no. 5
    
6.Ragge NK, Lorenz B, Schneider A, Bushby K, de Sanctis L, de Sanctis U, et al. SOX2 anophthalmia syndrome. Am J Med Genet A 2005;135:1-7.  Back to cited text no. 6
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7.Kelberman D, Rizzoti K, Avilion A, Bitner-Glindzicz M, Cianfarani S, Collins J, et al. Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans. J Clin Invest 2006;116:2442-55.  Back to cited text no. 7
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8.Zenteno JC, Gascon-Guzman G, Tovilla-Canales JL. Bilateral anophthalmia and brain malformations caused by a 20-bp deletion in the SOX2 gene. Clin Genet 2005;68:564-6.  Back to cited text no. 8
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9.Bakrania P, Robinson DO, Bunyan DJ, Salt A, Martin A, Crolla JA, et al. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. Br J Ophthalmol 2007;91:1471-6.  Back to cited text no. 9
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10.Kelberman D, De Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, et al. SOX2 plays a critical role in the pituitary, forebrain, and eye during human embryonic development. J Clin Endocrinol Metab 2008;93:1865-73.  Back to cited text no. 10
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11.Tziaferi V, Kelberman D, Dattani MT. The role of SOX2 in hypogonadotropic hypogonadism. Sex Dev 2008;2:194-9.  Back to cited text no. 11
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12.Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, et al. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet 2006;15:1413-22.  Back to cited text no. 12
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13.Guichet A, Triau S, Lepinard C, Esculapavit C, Biquard F, Descamps P, et al. Prenatal diagnosis of primary anophthalmia with a 3q27 interstitial deletion involving SOX2. Prenat Diagn 2004;24:828-32.  Back to cited text no. 13
    
14.Sisodiya SM, Ragge NK, Cavalleri GL, Hever A, Lorenz B, Schneider A, et al. Role of SOX2 mutations in human hippocampal malformations and epilepsy. Epilepsia 2006;47:534-42.  Back to cited text no. 14
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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