Absence of 9q22-9qter in trisomy 9 does not prevent a Dandy-Walker phenotype

Abstract

We report on a female fetus with partial trisomy 9 due to a reciprocal translocation in the mother. Routine ultrasound examination at 23 weeks showed hypoplasia of the cerebellar vermis, dilated foramen Magendii, and dilatation of the cisterna magna. Due to the poor prognosis, the parents opted for termination of pregnancy. A postmortem examination confirmed caudal hypoplasia and dysplasia of the cerebellar vermis, resulting in a massively dilated foramen Magendii through which the enlarged cisterna magna communicated with the fourth ventricle. There was also micropolygyria indicating migration disorder. Cytogenetic studies showed a 47,XX,+der(9)t(7;9) (q35;q22.2)mat karyotype. Investigation of the parents revealed a translocation (7;9) (q35;q22.2) in the mother and a normal male karyotype in the father. We systematically searched the chromosome 9 gene map for genes that were trisomic in our fetus and genes that were located on the regions that had the normal two copies of genes. Genes that could potentially be involved in the formation of the Dandy-Walker phenotype are transcription factors or genes responsible for the regulation of normal in particular cerebral development but also adhesion molecules. We conclude that one cause for Dandy-Walker malformation could be a gene dosage effect of genes located on 9pter-9q22. In addition, it seems that absence of trisomy 9 in q22-pter does not prevent abnormal cerebellar development.

Dandy–Walker syndrome and chromosomal abnormalities

“…There have been at least 20 case reports on DWS cases complicated by trisomy 9 (Golden & Schoene 1993). These reports include cases complicated by DWS such as trisomy 9 mosaic syndrome (Bureau et al 1993;Tarani et al 1994;Murru et al 2002), partial trisomy 9 (Zacharias et al 1983;Hannam et al 1999;von Kaisenberg et al 2000;Chen et al 2002aChen et al , 2005Metzke-Heidemann et al 2004), tetrasomy 9p (Melaragno et al 1992;Cazorla et al 2003;Hengstschlager et al 2004), and complete trisomy 9 (McDuffie 1994). The number of these reports shows that DWS can be commonly encountered in chromosome 9.…”

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3)

“…[67] The bilateral ventriculomegaly and an enlarged cistern magna reported in fetus with partial trisomy 9 (pter → q22) and partial trisomy 21(q22.3- qter). [8] vonKaisenberg et al [9] reported a Dandy-Walker malformation and hypoplasia of the cerebellar vermis in a fetus with partial trisomy 9 and 7. Recently partial trisomy 9p (p 11.2 → pter) reported in a fetus with Dandy-Walker malformation and it was suggested that the 9 pter → 11.2 region critical for the development of Dandy-Walkermalformation and ventriculomegaly.…”

Diagnostico Y Manejo Perinatal De Trisomia 9

“…El cuadro clínico se caracteriza por fascie típica que incluye microcefalia, enoftalmo, hipertelorismo, puente ancho nasal, fisura palpebral entre otros; retardo mental; alteraciones cerebrales principalmente de la línea media; restricción del crecimiento; hipoplasia ungueal; hipotonía; y otras manifestaciones que comprometen esqueleto, corazón, riñón y genitales (12,14,15), la gran mayoría descrita en nuestro caso anteriormente.…”

“…También se ha descrito otras anormalidades como gliosis moderada, anormalidades del hipocampo, atrofia del cuerpo calloso, ventriculomegalia, hipoplasia del vermis cerebeloso, siringomielia y mielomeningocele (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”