Dandy-Walker malformation and Wisconsin syndrome

Novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions

Alessandro Ferraris, Laura Bernardini, Vesna Sabolic Avramovska, Ginevra Zanni, Sara Loddo, Elena Sukarova-Angelovska, Valentina Parisi, Anna Capalbo, Stefano Tumini, Lorena Travaglini, Francesca Mancini, Filip Duma, Sabina Barresi, Antonio Novelli, Eugenio Mercuri, Luigi Tarani, Enrico Bertini, Bruno Dallapiccola, Enza Maria Valente

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Methods and results. Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Conclusions: Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.

Original languageEnglish
Article number75
JournalOrphanet Journal of Rare Diseases
Volume8
Issue number1
DOIs
Publication statusPublished - 2013

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Dandy-Walker Syndrome
Genetic Association Studies
Single Nucleotide Polymorphism
Genes
Phenotype
Penetrance
Magnetic Resonance Imaging

Keywords

  • 3q deletion
  • Dandy-Walker malformation
  • Wisconsin syndrome
  • ZIC1-ZIC4 genes

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Dandy-Walker malformation and Wisconsin syndrome : Novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions. / Ferraris, Alessandro; Bernardini, Laura; Sabolic Avramovska, Vesna; Zanni, Ginevra; Loddo, Sara; Sukarova-Angelovska, Elena; Parisi, Valentina; Capalbo, Anna; Tumini, Stefano; Travaglini, Lorena; Mancini, Francesca; Duma, Filip; Barresi, Sabina; Novelli, Antonio; Mercuri, Eugenio; Tarani, Luigi; Bertini, Enrico; Dallapiccola, Bruno; Valente, Enza Maria.

In: Orphanet Journal of Rare Diseases, Vol. 8, No. 1, 75, 2013.

Research output: Contribution to journalArticle

Ferraris, A, Bernardini, L, Sabolic Avramovska, V, Zanni, G, Loddo, S, Sukarova-Angelovska, E, Parisi, V, Capalbo, A, Tumini, S, Travaglini, L, Mancini, F, Duma, F, Barresi, S, Novelli, A, Mercuri, E, Tarani, L, Bertini, E, Dallapiccola, B & Valente, EM 2013, 'Dandy-Walker malformation and Wisconsin syndrome: Novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions', Orphanet Journal of Rare Diseases, vol. 8, no. 1, 75. https://doi.org/10.1186/1750-1172-8-75
Ferraris, Alessandro ; Bernardini, Laura ; Sabolic Avramovska, Vesna ; Zanni, Ginevra ; Loddo, Sara ; Sukarova-Angelovska, Elena ; Parisi, Valentina ; Capalbo, Anna ; Tumini, Stefano ; Travaglini, Lorena ; Mancini, Francesca ; Duma, Filip ; Barresi, Sabina ; Novelli, Antonio ; Mercuri, Eugenio ; Tarani, Luigi ; Bertini, Enrico ; Dallapiccola, Bruno ; Valente, Enza Maria. / Dandy-Walker malformation and Wisconsin syndrome : Novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions. In: Orphanet Journal of Rare Diseases. 2013 ; Vol. 8, No. 1.
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abstract = "Background: The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Methods and results. Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Conclusions: Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.",
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AU - Ferraris, Alessandro

AU - Bernardini, Laura

AU - Sabolic Avramovska, Vesna

AU - Zanni, Ginevra

AU - Loddo, Sara

AU - Sukarova-Angelovska, Elena

AU - Parisi, Valentina

AU - Capalbo, Anna

AU - Tumini, Stefano

AU - Travaglini, Lorena

AU - Mancini, Francesca

AU - Duma, Filip

AU - Barresi, Sabina

AU - Novelli, Antonio

AU - Mercuri, Eugenio

AU - Tarani, Luigi

AU - Bertini, Enrico

AU - Dallapiccola, Bruno

AU - Valente, Enza Maria

PY - 2013

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N2 - Background: The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Methods and results. Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Conclusions: Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.

AB - Background: The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Methods and results. Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Conclusions: Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.

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