A rare de novo unbalanced complex rearrangement involving chromosomes 12, 18 and 20 in a child with dysmorphic features

Abstract

Complex chromosomal rearrangements (CCRs) are rare structural abnormalities that involve three or more breakpoints located on two or more chromosomes and are often associated with developmental delay, mental retardation and congenital anomalies. Here, we report the case of a rare de novo CCR in a girl who was 9 months old when first reported to us. At 15 months old, her clinical features included marked hypotonia, severe psychomotor delay, progressive postnatal microcephaly, strabismus, depressed nasal root, hands and feet malformations, heart defects, recurrent respiratory infections and bilateral hearing deficit still in study. Conventional cytogenetic analysis revealed an unbalanced complex rearrangement, involving chromosomes 12, 18 and 20, and an apparent loss of material of chromosome 18 resulting from an interstitial deletion. Further molecular cytogenetic studies were performed: whole chromosome painting probes for the involved chromosomes and chromosomal comparative genomic hybridization. These studies revealed that apparently no other chromosomes were involved and confirmed a del(18)(q21.1q22) of approximately 17 Mb on the derivative chromosome 18. The latter chromosome also had material from der(12) to der(20) in its constitution. As most CCRs involving chromosome 18q show rearrangements in the q21, some authors argue that this region might be a breakpoint “hotspot”. On the other hand, cases of single deletions on 18q are predominantly terminal. Interstitial deletions are much rarer, and to our knowledge, this is the first report of a CCR with a del(18)(q21.1q22). The phenotype of patients with deletions within this region, reported so far, seems very similar to the one of our patient, and this may contribute to a better understanding of the genotype–phenotype correlation in this type of structural abnormalities.