Dandy-Walker Malformation Complex
ABSTRACT This autopsy-based study was designed to evaluate sonographic and neuropathologic findings of fetuses diagnosed prenatally with Dandy-Walker malformation complex.
The retrospective study encompassed a series of 44 autopsy cases from 2 tertiary referral centers with a prenatal ultrasound diagnosis of Dandy-Walker malformation complex between 1995 and 2003. Ultrasound and pathology data from the cases and from age-matched controls were reviewed in a blinded manner. An unequivocal diagnosis of Dandy-Walker malformation complex from ultrasonography or pathology archival images required significant hypoplasia or aplasia of the cerebellar vermis.
Neuropathologic examination failed to confirm the prenatal diagnosis of Dandy-Walker malformation complex in 59% (26/44, 95% confidence interval [CI] 44-72) of the cases. After standardized reevaluation of high quality archival sonograms and pathology images, concordance remained poor at 55% (6/11 cases, 95% CI 28-79). Sonographic features that favored concordance included marked enlargement of the cisterna magna (> or = 10 mm), complete aplasia of the vermis, and a trapezoid-shaped gap between the cerebellar hemispheres. This latter finding contrasted with a keyhole-shaped gap in fetuses with no cerebellar neuropathology.
Correlation between a prenatal ultrasound diagnosis of Dandy-Walker malformation complex and autopsy neuropathology findings is poor. Unequivocal prenatal sonographic diagnosis of Dandy-Walker malformation complex should be reserved for cases with the classic findings of Dandy-Walker malformation, including enlargement of the cisterna magna, aplasia of the vermis, and a trapezoid-shaped, rather than keyhole-shaped, interhemispheric gap.
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- "Early diagnosis is more difficult when extracranial findings are not present, because CVH cannot be reliably diagnosed until 18–20 weeks gestation [Bromley et al., 1994], and the MTS has not been reported prior to 27 weeks gestation [Fluss et al., 2006]. In the absence of a family history, prenatal diagnosis is possible but challenging given the spectrum of outcomes for isolated prenatal CVH [Phillips et al., 2006]. An imaging protocol for prenatal diagnosis has been proposed, although its sensitivity and specificity for JSRD have not been systematically evaluated [Doherty et al., 2005]. "
ABSTRACT: Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least eight genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium.American Journal of Medical Genetics Part C Seminars in Medical Genetics 11/2009; 151C(4):326-40. DOI:10.1002/ajmg.c.30229 · 3.91 Impact Factor
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- "This approach may aid in the detection of novel genomic loci for this condition, which in turn may improve its diagnosis. In view of the reported inconsistencies between results based on prenatal ultrasound examination and post mortem analysis [Phillips et al., 2006] there is a clear need for improved diagnosis. The strongly differing prognosis of patients with different genetic abnormalities (compare our patient with the one reported by O ˜ unap et al.  "
ABSTRACT: A 10-year-old boy with vermis hypoplasia, dilatation of the fourth ventricle, enlarged cisterna magna and aplasia of the corpus callosum, consistent with the Dandy-Walker complex (DWC), and slight facial dysmorphisms, severe motor and mental retardation is presented. By combining data obtained by karyotyping, array-CGH, FISH, and multiplex ligation-mediated probe amplification (MLPA) we identified a 5 Mb deletion of the 1q44 --> qter region resulting from a paternal t(1;20)(q44;q13.33). This smallest 1q44 deletion reported so far, enabled us to significantly narrow down the number of candidate genes for the DWC in this region. Since the ZNF124 transcription factor is strongly expressed in the fetal brain it may represent a candidate gene for the DWC at 1q44.American Journal of Medical Genetics Part A 05/2007; 143A(10):1038-44. DOI:10.1002/ajmg.a.31690 · 2.16 Impact Factor
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ABSTRACT: Both clinical and postmortem diagnoses of posterior fossa anomalies remain difficult to make and to corroborate. This is particularly true for Dandy-Walker malformation and variant. Difficulties arise for a variety of reasons, including technical and methodological ones, but also because the conditions may overlap anatomically with others, most notably mega cisterna magna, Blake's pouch cyst, and posterior fossa (arachnoid) cysts. Family counseling is difficult and complicated not only by diagnostic uncertainties but by the highly variable prognosis. In this study, a systematic pathologic approach to study of the posterior fossa is put forth. The benefits of postmortem imaging and in situ and ex situ examination of posterior fossa contents are demonstrated. Normative data for cerebellar width (transverse cerebellar diameter) and height and vermian width and height are derived for the fetal period. These data will help workers recognize changes in these structures, particularly hypoplasia. Basic morphologic definitions of posterior fossa anomalies are advanced, in the hopes that better agreement can be reached between clinical and pathologic diagnoses and that better patient and family care will result.Birth Defects Research Part A Clinical and Molecular Teratology 09/2006; 76(9):674-84. DOI:10.1002/bdra.20296 · 2.09 Impact Factor