Constitutional Chromothripsis on Chromosome 2: A Rare Case with Severe Presentation

Chromothripsis is characterized by shattering and subsequent reassembly of chromosomes by DNA repair processes, which can give rise to a variety of congenital abnormalities and cancer. Constitutional chromothripsis is a rare occurrence, reported in children presenting with a wide range of birth defects. We present a case of a female child born with multiple major congenital abnormalities including severe microcephaly, ocular dysgenesis, heart defect, and imperforate anus. Chromosomal microarray and mate pair sequencing identified a complex chromosomal rearrangement involving the terminal end of the long arm of chromosome 2, with two duplications (located at 2p25.3-p25.1 and 2q35-q37.2 regions) and two deletions (located at 2q37.2-q37.3 and 2q37.3 regions) along with structural changes including inverted segments. A review of the literature for complex rearrangements on chromosome 2 revealed overlapping features; however, our patient had a significantly more severe phenotype which resulted in early death at the age of 2 years. Breakpoints analysis did not reveal the involvement of any candidate genes. We concluded that the complexity of the genomic rearrangement and the combined dosage/structural effect of these copy number variants are likely explanations for the severe presentation in our patient.