Complex genomic rearrangements of the Y chromosome in a premature infant.

BACKGROUND

Chromoanagenesis is an umbrella term used to describe catastrophic "all at once" cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline. The clinical features associated with constitutional chromoanagenesis are typically due to copy number changes and/or disruption of genes or regulatory regions.

CASE PRESENTATION: We present an 8-year-old male patient with complex rearrangements of the Y chromosome including a ring Y chromosome, a derivative Y;21 chromosome, and a complex rearranged Y chromosome. These chromosomes were characterized by G-banded chromosome analysis, SNP microarray, interphase FISH, and metaphase FISH. The mechanism(s) by which these rearrangements occurred is unclear; however, it is evocative of chromoanagenesis.

CONCLUSION

This case is a novel example of suspected germline chromoanagenesis leading to large copy number changes that are well-tolerated, possibly because only the sex chromosomes are affected.