A new case of cryptic unbalanced t(1:12)(q44;p13.3) translocation with polymicrogyria

Neurological disorders and seizures have been reported for most of the patients with del(1q) syndrome, but polymicrogyria (PMG) has been described only in two patients affected by a familial unbalanced translocation with 1q44qter monosomy and 12p13.3pter trisomy. PMG is a malformation in which the brain surface is irregular and the normal pattern is replaced by multiple small gyri separated by shallow sulci, and it is possibly due to a defect in neuronal migration.Here we describe a new case of an unbalanced t(1;12) translocation with PMG in a five-year-old child presenting with facial dysmorphisms, mental retardation, microcephaly, corpus callosum and cerebellar hypoplasia, abnormal feet, hypospadia and seizures. No chromosomal anomalies were detected by standard cytogenetic analysis. Array CGH analysis, by Agilent 44K chip, unraveled a terminal 12Mb deletion of the q arm of chromosome 1 and a 3Mb duplication of the distal segment of chromosome 12p. Features of the proband were consistent with both the terminal del(1q) and the dup(12p) syndromes, except for PMG that has never been described in either rearrangement.As PMG seems to occur in t(1;12) translocations, we speculate that this defect might be caused by concomitant haploinsufficiency of 1q44 genes and trisomy of 12p distal genes. Candidate genes mapping in these chromosomal regions and related pathways involved in neuronal migration will be discussed