Cytogenomics and optical genome mapping approaches characterize a derivative interstitial monosomy 18p due to a maternal complex intrachromosomal rearrangement.

Abstract

Background: Monosomy 18p (MIM: 146390) is a well-known chromosomal disorder associated with intellectual disability, short stature, and non-specific craniofacial features resulting from partial or total deletion of the short arm of chromosome 18. The differential diagnosis is broad due to nonspecific and variable phenotypes. The majority of 18p monosomy cases result from de novo deletions, while the remainder are either caused by de novo translocation with loss of 18p, malsegregation of a parental translocation or inversion, or the presence of a ring chromosome or isochromosome 18q. Establishing the etiopathogenetic mechanism is essential to properly assess the risk of recurrence. Chromosomal Microarray Analysis (CMA) has enabled better genotype-phenotype correlations. Nonetheless, CMA is not appropriate for characterizing complex or balanced structural variants, which may underlie complex rearrangement, and the resolution of karyotype analysis is limited.

Case presentation: Here, we report the first case of a derivative 18p interstitial monosomy caused by a maternal complex intrachromosomal rearrangement, fully characterized by Optical Genome Mapping (OGM).

Conclusions: This rearrangement could not be fully characterized by either CMA or karyotype analyses, both of which yielded only partial and inconclusive results. The integration of OGM into routine diagnostics could enhance the understanding of complex chromosomal rearrangements, leading to improved prognostic and reproductive risk assessment.