Delineation variable genotype/phenotype correlations of 6q27 terminal deletion derived from dic(6;18)(q27;p10)

Background: Terminal deletion of 6q27 produces a rare syndrome associated with unexplained mental retardation, hypotonia, epilepsy, and multiple malformations. Structural brain malformations are consistently observed, including agenesis of the corpus callosum, hydrocephalus, periventricular nodular heterotopia, polymicrogyria, and cerebellar malformations. Here we report a fetal risk assessment of a 27-year-old woman with mental retardation, hypotonia and dysmorphic features at 17 weeks of pregnancy. Results: Cytogenetic analyses revealed an addition at chromosome 6qter in the mother. Haploinsufficiency of 6q27 to 6qter (1.3 Mb) and trisomy of the entire short arm of chromosome 18 (15.2 Mb) were found using a single nucleotide polymorphism based array. Results were confirmed by molecular cytogenetics and multiplex ligation-dependent probe amplification. The karyotype of the mother was 46,XX dic(6; 18)(6pter -> 6q27::18p10 -> 18pter).arr [hg19]6q27 (169,591,548-170,898,549) x 1,18p11.3p10(12,842-15,375,878) x 3.ish dic(6;18)(q27;p10)(RP11-614P3-,RP11-1035E2+,D18Z1+). Deletion of 6q27 was associated with the structural brain malformations, whereas trisomy of 18p had minor clinical effects. The unbalanced rearrangement of chromosome 6 and chromosome 18 was de novo and was not inherited by the developing fetus. Conclusions: A rare rearrangement between 6q27 and 18p was identified, which led to a de novo 1.3 Mb deletion of 6q27 and a 15.2 Mb duplication of 18p in an adult with mental retardation, hypotonia, epilepsy, and multiple malformations.