Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions

作者：Ferraris Alessandro; Bernardini Laura; Avramovska Vesna Sabolic; 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^*

来源：Orphanet Journal of Rare Diseases, 2013, 8(1): 75.

DOI：10.1186/1750-1172-8-75

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

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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2013-5-16