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

## TL;DR

A rare case of chromosomal abnormalities in a child led to severe birth defects and early death, likely due to complex genetic changes on chromosome 2.

## Contribution

This paper reports a rare and severe case of constitutional chromothripsis on chromosome 2 with a novel combination of genomic rearrangements.

## Key findings

- The patient had duplications and deletions on chromosome 2, leading to severe congenital abnormalities.
- Literature review showed overlapping features but no prior case with such a severe outcome.
- Breakpoints analysis found no candidate gene involvement, suggesting structural and dosage effects caused the severity.

## Abstract

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.