title: Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions.
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.
  
  
  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.
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Vesna
authors.initials: V
authors.lastname: Sabolic Avramovska
authors.forename: Ginevra
authors.initials: G
authors.lastname: Zanni
authors.forename: Sara
authors.initials: S
authors.lastname: Loddo
authors.forename: Elena
authors.initials: E
authors.lastname: Sukarova-Angelovska
authors.forename: Valentina
authors.initials: V
authors.lastname: Parisi
authors.forename: Anna
authors.initials: A
authors.lastname: Capalbo
authors.forename: Stefano
authors.initials: S
authors.lastname: Tumini
authors.forename: Lorena
authors.initials: L
authors.lastname: Travaglini
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Filip
authors.initials: F
authors.lastname: Duma
authors.forename: Sabina
authors.initials: S
authors.lastname: Barresi
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.forename: Luigi
authors.initials: L
authors.lastname: Tarani
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003616:Dandy-Walker Syndrome / Q000235:genetics* / Q000473:pathology*; D005145:Face / Q000002:abnormalities; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014922:Wisconsin; D055815:Young Adult; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D014157:Transcription Factors