Unbalanced der5t5;20 translocation associated with megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalusHow to cite this article: Verkerk AJMH, Schot R, van Waterschoot L, Douben H, Poddighe PJ, Lequin MH, de Vries LS, Terhal P, Hahnemann JMD, de Coo IFM, de Wit MCY, Wafelman LS, Garavelli L, Dobyns WB, Van der Spek PJ, de Klein A, Mancini GMS. 2010. Unbalanced der5t5;20 translocation associated with megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalus. Am J Med Genet Part A 152A:1488–1497.

The combination of megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalus MPPH is a rare syndrome of unknown cause. We observed two first cousins affected by an MPPHlike phenotype with a submicroscopic chromosome 5q35 deletion as a result of an unbalanced der5t5;20q35.2;q13.3 translocation, including the NSD1Sotos syndrome locus. We describe the phenotype and the deletion breakpoints of the two MPPHlike patients and compare these with five unrelated MPPH and Sotos patients harboring a 5q35 microdeletion. Mapping of the breakpoints in the two cousins was performed by MLPA, FISH, high density SNParrays and QPCR for the 5q35 deletion and 20q13 duplication. The 5q35 deletion area of the two cousins almost completely overlaps with earlier described patients with an atypical Sotos microdeletion, except for the DRD1gene. The five unrelated MPPH patients neither showed submicroscopic chromosomal aberrations nor DRD1mutations. We reviewed the brain MRI of 10 Sotos patients and did not detect polymicrogyria in any of them. In our two cousins, the MPPHlike phenotype is probably caused by the contribution of genes on both chromosome 5q35 and 20q13. Some patients with MPPH may harbor a submicroscopic chromosomal aberration and therefore highresolution array analysis should be part of the diagnostic workup. © 2010 WileyLiss, Inc.