title: Unbalanced der(5)t(5;20) translocation associated with megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalus.
abstract: 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 MPPH-like phenotype with a submicroscopic chromosome 5q35 deletion as a result of an unbalanced der(5)t(5;20)(q35.2;q13.3) translocation, including the NSD1 Sotos syndrome locus. We describe the phenotype and the deletion breakpoints of the two MPPH-like 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 SNP-arrays and Q-PCR 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 DRD1 gene. The five unrelated MPPH patients neither showed submicroscopic chromosomal aberrations nor DRD1 mutations. We reviewed the brain MRI of 10 Sotos patients and did not detect polymicrogyria in any of them. In our two cousins, the MPPH-like 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 high-resolution array analysis should be part of the diagnostic workup.
authors.affiliation: Department of Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Annemieke J M H
authors.initials: AJ
authors.lastname: Verkerk
authors.forename: Rachel
authors.initials: R
authors.lastname: Schot
authors.forename: Laura
authors.initials: L
authors.lastname: van Waterschoot
authors.forename: Hannie
authors.initials: H
authors.lastname: Douben
authors.forename: Pino J
authors.initials: PJ
authors.lastname: Poddighe
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Lequin
authors.forename: Linda S
authors.initials: LS
authors.lastname: de Vries
authors.forename: Paulien
authors.initials: P
authors.lastname: Terhal
authors.forename: Johanne M D
authors.initials: JM
authors.lastname: Hahnemann
authors.forename: Irenaeus F M
authors.initials: IF
authors.lastname: de Coo
authors.forename: Marie-Claire Y
authors.initials: MC
authors.lastname: de Wit
authors.forename: Leontien S
authors.initials: LS
authors.lastname: Wafelman
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Van der Spek
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.forename: Grazia M S
authors.initials: GM
authors.lastname: Mancini
mesh_terms: D001921:Brain / Q000002:abnormalities; D002675:Child, Preschool; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000175:diagnosis / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D018810:Magnetic Resonance Angiography; D008297:Male; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D017689:Polydactyly / Q000175:diagnosis / Q000235:genetics*; D017384:Sequence Deletion; D013577:Syndrome; D014178:Translocation, Genetic