A complex chromosome rearrangement involving four chromosomes, nine breakpoints and a cryptic 0.6-Mb deletion in a boy with cerebellar hypoplasia and defects in skull ossification.

Constitutional complex chromosomal rearrangements (CCRs) are considered rare cytogenetic events. Most apparently balanced CCRs are de novo and are usually found in patients with abnormal phenotypes. High-resolution techniques are unveiling genomic imbalances in a great percentage of these cases. In this paper, we report a patient with growth and developmental delay, dysmorphic features, nervous system anomalies (pachygyria, hypoplasia of the corpus callosum and cerebellum), a marked reduction in the ossification of the cranial vault, skull base sclerosis, and cardiopathy who presents a CCR with 9 breakpoints involving 4 chromosomes (3, 6, 8 and 14) and a 0.6-Mb deletion in 14q24.1. Although the only genomic imbalance revealed by the array technique was a deletion, the clinical phenotype of the patient most likely cannot be attributed exclusively to haploinsufficiency. Other events must also be considered, including the disruption of critical genes and position effects. A combination of several different investigative approaches (G-banding, FISH with different probes and SNP array techniques) was required to describe this CCR in full, suggesting that CCRs may be more frequent than initially thought. Additionally, we propose that a chain chromosome breakage mechanism may have occurred as a single rearrangement event resulting in this CCR. This study demonstrates the importance of applying different cytogenetic and molecular techniques to detect subtle rearrangements and to delineate the rearrangements at a more accurate level, providing a better understanding of the mechanisms involved in CCR formation and a better correlation with phenotype.

Optic disc topography in pseudopapilledema: a comparison to pseudotumor cerebri.

OBJECTIVES: To determine if confocal scanning laser (CSL) tomography can quantify optic disc topography in patients with pseudopapilledema (PP) and to contrast the regional topography of the optic disc in PP and pseudotumor cerebri (PTC). MATERIALS AND METHODS: Three-dimensional optic disc images from 10 PP patients PP and 17 PTC patients were obtained using the Heidelberg Retinal Tomograph (HRT). Two conventional HRT parameters, volume above the reference plane and volume above the surface, were used to quantify global disc elevation. In addition, local topography was determined at 100 microm intervals along eight meridians at 100 to 1700 microm from the disc center. The global and local measures of disc topography in the two groups were compared statistically. RESULTS: Significant between group differences were detected for both global measures. Regional analysis revealed vertical symmetry and horizontal asymmetry in PP and PTC as well as significant between group differences in peripapillary height. CONCLUSIONS: CSL tomography can quantify disc elevation in both PP and PTC and may be useful for differentiating disc morphology in PP and PTC. The volume of the disc above the retinal surface is greater in PTC than in PP. However, most of the difference in elevation between the two groups occurs over the disc rim and peripapillary retina.