Uniparental Disomy: A Scoping Review of Diagnostic Challenges, Clinical Spectrum, and Counselling Implications

Uniparental disomy (UPD) is a rare chromosomal anomaly causing significant clinical implications in many affected individuals. In the case of UPD, a pair of homologous chromosomes or segments of it is inherited from only one parent. This can disrupt genomic imprinting, create long stretches of homozygosity, leading to diverse genetic and epigenetic syndromes. This scoping review has aimed to summarize postnatally reported UPD cases, tabulate chromosomespecific clinical characteristics, molecular diagnostic methodologies being utilized, and to formulate a standardised diagnostic workflow.

A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to 28 March 2025. Postnatally reported UPD cases were included. Extracted data comprised involved chromosomes, parental origin of disomy, clinical presentation of the affected individuals, and diagnostic approaches utilized.

A total of 1507 UPD cases from 632 studies were analysed. UPDs were reported across all chromosomes, with the highest prevalence in chromosomes 11 (24.30%), 15 (18.64%), 7 (13.04%), and 14 (12.11%). The least affected were chromosomes 3, 9, 10, 12, 13, 17, 18, 19, 21, and X (<1% each). Mosaic UPD was identified in 15% of cases. Among the published cases, common clinical features included developmental delay, growth restriction, intellectual disability, and craniofacial dysmorphism. Most frequently employed diagnostic techniques included microsatellite/STR marker analysis, SNP microarray, methylation-specific MLPA, and whole-exome sequencing.

Among all the chromosomes involved in UPD, the highest clinical relevance is observed in chromosomes 7, 11, 14, and 15. Among the techniques utilized for the detection and confirmation of UPDs, microsatellite/STR analysis is considered the gold standard. For higher efficiency and accuracy, better clinical interpretations, and proper genetic counselling opportunities, an integrated diagnostic workflow strategically targeting both genetic and epigenetic aspects is required.

In this review, the clinical impact of different types of UPDs involving various chromosomes is highlighted. An integrated (epi/genetic) approach as a diagnostic framework is proposed.