Topic: Rare Neurodevelopmental Disorders: From Genetics to Evidence-Based Clinical Management

Neurodevelopmental disorders (NDDs) are early-onset clinical conditions characterized by cognitive and/or behavioral symptoms that result in social, academic, and work-related impairment, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). NDDs include intellectual disability, autism spectrum disorder, and rare genetic disorders, all of which typically manifest during childhood.

The etiopathogenesis of NDDs is multifactorial, involving a strong genetic component influenced by various environmental factors, most of which remain poorly understood. Rare NDDs encompass a spectrum of neurodevelopmental conditions affecting fewer than 1 in 2,000 individuals in Europe.

Early diagnosis and timely intervention are critical for managing rare NDDs, particularly given the limited knowledge regarding their developmental, cognitive, and behavioral trajectories. Defining the cognitive and behavioral profiles of individuals with rare genetic syndromes represents a crucial research and clinical priority. In many cases, medical management of organic or somatic defects may divert attention from the evaluation of developmental profiles. Yet, these profiles are key predictors of long-term outcomes in adulthood (including learning abilities and levels of independence) and are among the main concerns of parents of children with chronic conditions. This highlights the need for focused research in this area.

This Special Issue on “Rare Neurodevelopmental Disorders: From Genetics to Evidence-Based Clinical Management” aims to collect high-quality contributions addressing this complex field, with particular focus on:

● The natural history and characterization of developmental profiles and longitudinal trajectories of rare NDDs, including cognitive and behavioral phenotypes;

● Diagnostic challenges in the early detection of NDDs: from genetic analysis to clinical evaluation;

● The management of rare NDDs: implications for clinicians and families;

● Perspectives on interventions for rare NDDs;

● Animal models of rare NDDs.