Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients

L. Garavelli, I. Ivanovski, S. G. Caraffi, D. Santodirocco, M. Pollazzon, D. M. Cordelli, E. Abdalla, P. Accorsi, M. P. Adam, C. Baldo, A. Bayat, E. Belligni, F. Bonvicini, J. Breckpot, B. Callewaert, G. Cocchi, G. Cuturilo, K. Devriendt, M. B. Dinulos, O. DjuricR. Epifanio, F. Faravelli, D. Formisano, L. Giordano, M. Grasso, S. Gronborg, A. Iodice, L. Iughetti, D. Lacombe, M. Maggi, B. Malbora, I. Mammi, S. Moutton, R. Moller, P. Muschke, M. Napoli, C. Pantaleoni, R. Pascarella, A. Pellicciari, M. L. Poch-Olive, F. Raviglione, F. Rivieri, C. Russo, S. Savasta, G. Scarano, A. Selicorni, M. Silengo, G. Sorge, L. Tarani, N. Zanotta

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.
Original languageEnglish
Pages (from-to)691-700
Number of pages10
JournalGenetics in Medicine
Volume19
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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Neuroimaging
Brain
Magnetic Resonance Imaging
Agenesis of Corpus Callosum
Viverridae
Haploinsufficiency
Cerebral Ventricles
Hirschsprung Disease
Inborn Genetic Diseases
Congenital Heart Defects
Corpus Callosum
Genetic Association Studies
Basal Ganglia
Intellectual Disability
Publications
Epilepsy
Phenotype
Mowat-Wilson syndrome
Genes
Proteins

Keywords

  • Brain/diagnostic imaging/pathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Epilepsy/pathology
  • Facies
  • Female
  • Genotype
  • Haploinsufficiency
  • Hirschsprung Disease/diagnostic imaging/genetics/pathology
  • Humans
  • Infant
  • Intellectual Disability/diagnostic imaging/genetics/pathology
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Microcephaly/diagnostic imaging/genetics/pathology
  • Neuroimaging
  • Phenotype
  • Zinc Finger E-box Binding Homeobox 2/genetics

Cite this

Garavelli, L., Ivanovski, I., Caraffi, S. G., Santodirocco, D., Pollazzon, M., Cordelli, D. M., ... Zanotta, N. (2017). Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients. Genetics in Medicine, 19(6), 691-700. https://doi.org/10.1038/gim.2016.176 [doi]

Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients. / Garavelli, L.; Ivanovski, I.; Caraffi, S. G.; Santodirocco, D.; Pollazzon, M.; Cordelli, D. M.; Abdalla, E.; Accorsi, P.; Adam, M. P.; Baldo, C.; Bayat, A.; Belligni, E.; Bonvicini, F.; Breckpot, J.; Callewaert, B.; Cocchi, G.; Cuturilo, G.; Devriendt, K.; Dinulos, M. B.; Djuric, O.; Epifanio, R.; Faravelli, F.; Formisano, D.; Giordano, L.; Grasso, M.; Gronborg, S.; Iodice, A.; Iughetti, L.; Lacombe, D.; Maggi, M.; Malbora, B.; Mammi, I.; Moutton, S.; Moller, R.; Muschke, P.; Napoli, M.; Pantaleoni, C.; Pascarella, R.; Pellicciari, A.; Poch-Olive, M. L.; Raviglione, F.; Rivieri, F.; Russo, C.; Savasta, S.; Scarano, G.; Selicorni, A.; Silengo, M.; Sorge, G.; Tarani, L.; Zanotta, N.

In: Genetics in Medicine, Vol. 19, No. 6, 01.06.2017, p. 691-700.

Research output: Contribution to journalArticle

Garavelli, L, Ivanovski, I, Caraffi, SG, Santodirocco, D, Pollazzon, M, Cordelli, DM, Abdalla, E, Accorsi, P, Adam, MP, Baldo, C, Bayat, A, Belligni, E, Bonvicini, F, Breckpot, J, Callewaert, B, Cocchi, G, Cuturilo, G, Devriendt, K, Dinulos, MB, Djuric, O, Epifanio, R, Faravelli, F, Formisano, D, Giordano, L, Grasso, M, Gronborg, S, Iodice, A, Iughetti, L, Lacombe, D, Maggi, M, Malbora, B, Mammi, I, Moutton, S, Moller, R, Muschke, P, Napoli, M, Pantaleoni, C, Pascarella, R, Pellicciari, A, Poch-Olive, ML, Raviglione, F, Rivieri, F, Russo, C, Savasta, S, Scarano, G, Selicorni, A, Silengo, M, Sorge, G, Tarani, L & Zanotta, N 2017, 'Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients', Genetics in Medicine, vol. 19, no. 6, pp. 691-700. https://doi.org/10.1038/gim.2016.176 [doi]
Garavelli L, Ivanovski I, Caraffi SG, Santodirocco D, Pollazzon M, Cordelli DM et al. Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients. Genetics in Medicine. 2017 Jun 1;19(6):691-700. https://doi.org/10.1038/gim.2016.176 [doi]
Garavelli, L. ; Ivanovski, I. ; Caraffi, S. G. ; Santodirocco, D. ; Pollazzon, M. ; Cordelli, D. M. ; Abdalla, E. ; Accorsi, P. ; Adam, M. P. ; Baldo, C. ; Bayat, A. ; Belligni, E. ; Bonvicini, F. ; Breckpot, J. ; Callewaert, B. ; Cocchi, G. ; Cuturilo, G. ; Devriendt, K. ; Dinulos, M. B. ; Djuric, O. ; Epifanio, R. ; Faravelli, F. ; Formisano, D. ; Giordano, L. ; Grasso, M. ; Gronborg, S. ; Iodice, A. ; Iughetti, L. ; Lacombe, D. ; Maggi, M. ; Malbora, B. ; Mammi, I. ; Moutton, S. ; Moller, R. ; Muschke, P. ; Napoli, M. ; Pantaleoni, C. ; Pascarella, R. ; Pellicciari, A. ; Poch-Olive, M. L. ; Raviglione, F. ; Rivieri, F. ; Russo, C. ; Savasta, S. ; Scarano, G. ; Selicorni, A. ; Silengo, M. ; Sorge, G. ; Tarani, L. ; Zanotta, N. / Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients. In: Genetics in Medicine. 2017 ; Vol. 19, No. 6. pp. 691-700.
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title = "Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients",
abstract = "PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6{\%} of cases), hippocampal abnormalities (77.8{\%}), enlargement of cerebral ventricles (68.5{\%}), and white matter abnormalities (reduction of thickness 40.7{\%}, localized signal alterations 22.2{\%}). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.",
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author = "L. Garavelli and I. Ivanovski and Caraffi, {S. G.} and D. Santodirocco and M. Pollazzon and Cordelli, {D. M.} and E. Abdalla and P. Accorsi and Adam, {M. P.} and C. Baldo and A. Bayat and E. Belligni and F. Bonvicini and J. Breckpot and B. Callewaert and G. Cocchi and G. Cuturilo and K. Devriendt and Dinulos, {M. B.} and O. Djuric and R. Epifanio and F. Faravelli and D. Formisano and L. Giordano and M. Grasso and S. Gronborg and A. Iodice and L. Iughetti and D. Lacombe and M. Maggi and B. Malbora and I. Mammi and S. Moutton and R. Moller and P. Muschke and M. Napoli and C. Pantaleoni and R. Pascarella and A. Pellicciari and Poch-Olive, {M. L.} and F. Raviglione and F. Rivieri and C. Russo and S. Savasta and G. Scarano and A. Selicorni and M. Silengo and G. Sorge and L. Tarani and N. Zanotta",
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TY - JOUR

T1 - Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients

AU - Garavelli, L.

AU - Ivanovski, I.

AU - Caraffi, S. G.

AU - Santodirocco, D.

AU - Pollazzon, M.

AU - Cordelli, D. M.

AU - Abdalla, E.

AU - Accorsi, P.

AU - Adam, M. P.

AU - Baldo, C.

AU - Bayat, A.

AU - Belligni, E.

AU - Bonvicini, F.

AU - Breckpot, J.

AU - Callewaert, B.

AU - Cocchi, G.

AU - Cuturilo, G.

AU - Devriendt, K.

AU - Dinulos, M. B.

AU - Djuric, O.

AU - Epifanio, R.

AU - Faravelli, F.

AU - Formisano, D.

AU - Giordano, L.

AU - Grasso, M.

AU - Gronborg, S.

AU - Iodice, A.

AU - Iughetti, L.

AU - Lacombe, D.

AU - Maggi, M.

AU - Malbora, B.

AU - Mammi, I.

AU - Moutton, S.

AU - Moller, R.

AU - Muschke, P.

AU - Napoli, M.

AU - Pantaleoni, C.

AU - Pascarella, R.

AU - Pellicciari, A.

AU - Poch-Olive, M. L.

AU - Raviglione, F.

AU - Rivieri, F.

AU - Russo, C.

AU - Savasta, S.

AU - Scarano, G.

AU - Selicorni, A.

AU - Silengo, M.

AU - Sorge, G.

AU - Tarani, L.

AU - Zanotta, N.

N1 - LR: 20180213; GR: GEP14131/Telethon/Italy; GR: K08 NS078054/NS/NINDS NIH HHS/United States; GR: R01 NS050375/NS/NINDS NIH HHS/United States; JID: 9815831; 0 (ZEB2 protein, human); 0 (Zinc Finger E-box Binding Homeobox 2); Mowat-Wilson syndrome; EMS70054; 2016/05/27 00:00 [received]; 2016/09/22 00:00 [accepted]; 2016/11/11 06:00 [pubmed]; 2018/02/14 06:00 [medline]; 2016/11/11 06:00 [entrez]; ppublish

PY - 2017/6/1

Y1 - 2017/6/1

N2 - PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.

AB - PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.

KW - Brain/diagnostic imaging/pathology

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Epilepsy/pathology

KW - Facies

KW - Female

KW - Genotype

KW - Haploinsufficiency

KW - Hirschsprung Disease/diagnostic imaging/genetics/pathology

KW - Humans

KW - Infant

KW - Intellectual Disability/diagnostic imaging/genetics/pathology

KW - Longitudinal Studies

KW - Magnetic Resonance Imaging

KW - Male

KW - Microcephaly/diagnostic imaging/genetics/pathology

KW - Neuroimaging

KW - Phenotype

KW - Zinc Finger E-box Binding Homeobox 2/genetics

U2 - 10.1038/gim.2016.176 [doi]

DO - 10.1038/gim.2016.176 [doi]

M3 - Article

VL - 19

SP - 691

EP - 700

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 6

ER -