Imprinting disorders and multiple imprinting abnormalities (multilocus imprinting disturbances): new diagnoses, new perspectives.

Abstract

Imprinting disorders result from (epi)genetic abnormalities affecting genomic regions whose expression depends on parental origin. Among these, multilocus imprinting disturbances (MLID) constitute a specific entity characterised by simultaneous alterations in several imprinted regions, often leading to complex phenotypes. In recent years, the identification of maternal genetic factors, particularly within the maternal subcortical complex (SCMC), has led to a better understanding of the origin of certain cases of MLID. At the same time, rapid advances in molecular analysis-methylation arrays, targeted NGS panels, and long-read sequencing approaches-have profoundly renewed diagnostic capabilities. Together, these advances now offer a more integrated view of the mechanisms, phenotypes, and genetic determinants of imprinting-related diseases.