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 language | English |
|---|---|
| Article number | 75 |
| Journal | Orphanet Journal of Rare Diseases |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Dandy-Walker malformation and Wisconsin syndrome
T2 - Novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions
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
Y1 - 2013
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.
KW - 3q deletion
KW - Dandy-Walker malformation
KW - Wisconsin syndrome
KW - ZIC1-ZIC4 genes
UR - http://www.scopus.com/inward/record.url?scp=84878462305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878462305&partnerID=8YFLogxK
U2 - 10.1186/1750-1172-8-75
DO - 10.1186/1750-1172-8-75
M3 - Article
C2 - 23679990
AN - SCOPUS:84878462305
VL - 8
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
IS - 1
M1 - 75
ER -