Clinical and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders

Monogenic Diabetes Mellitus refers to heterogeneous forms of diabetes mellitus (DM) caused by a single gene pathogenic variant. Neurodevelopmental disorders (NDDs) are clinically and molecularly heterogeneous conditions characterized by an impairment of the nervous system development and/or function, with a wide clinical spectrum of variability. Over the last decade, Next Generation Sequencing (NGS) approaches have played a crucial role in the discovery of many monogenic causes underlying both NDDs and diabetes. In this systematic review, we aim to overview novel and emerging monogenic diseases presenting with pediatric diabetes and concomitant NDDs. The literature search was run in PubMed and Embase with a set of appropriate keywords. We examined 26 articles. Pathogenic variants have been classified according to the age of diabetes onset. In-depth analysis has been conducted for the selected papers, focusing on clinical description and molecular implications for a definite disease-causing gene. Interesting papers have revealed in recent years the occurrence of potential shared disease mechanisms underlying glucose and insulin metabolism and brain development and function. The broad clinical and molecular spectrum of DM-associated NDDs highlights the importance of a comprehensive and multidisciplinary management of these emerging clinical conditions and the increasingly crucial role of appropriate therapeutic approaches.