Article

Dandy-Walker Malformation Associated With Heterozygous ZIC1 and ZIC4 Deletion: Report of a New Patient

Department of Pediatrics, Nishi-Niigata Chuo National Hospital, Japan.
American Journal of Medical Genetics Part A (Impact Factor: 2.3). 01/2011; 155A(1):130-3. DOI: 10.1002/ajmg.a.33652
Source: PubMed

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.

0 Bookmarks
 · 
158 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the last 60 years, the spotlight of research has periodically returned to the cerebellum as new techniques and insights have emerged. Because of its simple homogeneous structure, limited diversity of cell types and characteristic behavioral pathologies, the cerebellum is a natural home for studies of cell specification, patterning, and neuronal migration. However, recent evidence has extended the traditional range of perceived cerebellar function to include modulation of cognitive processes and implicated cerebellar hypoplasia and Purkinje neuron hypo-cellularity with autistic spectrum disorder. In the light of this emerging frontier, we review the key stages and genetic mechanisms behind cerebellum development. In particular, we discuss the role of the midbrain hindbrain isthmic organizer in the development of the cerebellar vermis and the specification and differentiation of Purkinje cells and granule neurons. These developmental processes are then considered in relation to recent insights into selected human developmental cerebellar defects: Joubert syndrome, Dandy-Walker malformation, and pontocerebellar hypoplasia. Finally, we review current research that opens up the possibility of using the mouse as a genetic model to study the role of the cerebellum in cognitive function.
    Frontiers in Neuroanatomy 01/2013; 7:29. DOI:10.3389/fnana.2013.00029 · 4.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dandy-Walker malformation (DWM) is the most common human cerebellar malformation, characterized by hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and an enlarged posterior fossa with upward displacement of the lateral sinuses, tentorium, and torcular. Although its pathogenesis is not completely understood, there are several genetic loci related to DWM as well as syndromic malformations and congenital infections. Dandy-Walker malformation is associated with other central nervous system abnormalities, including dysgenesis of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube defects. Hydrocephalus plays an important role in the development of symptoms and neurological outcome in patients with DWM, and the aim of surgical treatment is usually the control of hydrocephalus and the posterior fossa cyst. Imaging modalities, especially magnetic resonance imaging, are crucial for the diagnosis of DWM and distinguishing this disorder from other cystic posterior fossa lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection with cerebrospinal fluid signal intensity and a median line communication with the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna presents as an extraaxial fluid collection posteroinferior to an intact cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar hemispheres and the fourth ventricle. Patients with DWM show an enlarged posterior fossa filled with a cystic structure that communicates freely with the fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is of utmost importance for understanding the cerebellar malformations, including DWM, and other related entities.
    Topics in magnetic resonance imaging: TMRI 12/2011; 22(6):303-12. DOI:10.1097/RMR.0b013e3182a2ca77
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of a neonate with proximal spinal muscular atrophy (SMA) type 1 (also known as Werdnig-Hoffmann disease or severe infantile acute SMA) associated with a Blake's pouch cyst; a malformation that is currently classified within the spectrum of Dandy-Walker complex. The association of the two conditions has not been previously reported in the English literature. A comprehensive review of the pertinent literature is presented.
    Surgical Neurology International 01/2014; 5(Suppl 4):S282-8. DOI:10.4103/2152-7806.139390 · 1.18 Impact Factor