title: Dandy-Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion: Report of a new patient.
abstract: We report on a female patient with Dandy-Walker malformation possibly caused by heterozygous loss of ZIC1 and ZIC4. The patient presented with mental retardation, epilepsy, and multiple congenital malformations including spina bifida, mild dysmorphic facial features including, thick eyebrows, broad nose, full lips, macroglossia, and hypoplasia of the cerebellar vermis with enlargement of the fourth ventricle on brain magnetic resonance imaging, which is consistent with Dandy-Walker malformation. A chromosome analysis showed interstitial deletion of chromosome 3q23-q25.1. Fluorescence in situ hybridization (FISH) and microarray-based genomic analysis revealed the heterozygous deletion of ZIC1 and ZIC4 loci on 3q24. Her facial features were not consistent with those observed in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) involving FOXL2 abnormality. Other deleted genes at 3q23-25.1 might contribute to the dysmorphic facial appearance. A milder phenotype as the Dandy-Walker malformation in our patient supports the idea that modifying loci/genes can influence the development of cerebellar malformation.
authors.affiliation: Department of Pediatrics, Nishi-Niigata Chuo National Hospital, Japan. jtohyama@masa.go.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Tohyama
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: Sari
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsui
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akasaka
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohashi
authors.forename: Yu
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003616:Dandy-Walker Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C492123:ZIC1 protein, human; C492799:ZIC4 protein, human