Longitudinal Behavior Phenotype Hallmarks in RNU4-2 Syndrome: Implications for Clinical Management.

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• Pathogenic variants in the RNU4-2 gene are a significant cause of neurodevelopmental disorders (NDDs).
• The longitudinal behavioral and neuropsychiatric phenotype of ReNU syndrome remains poorly understood.
• RNU4-2 variants account for approximately 0.4% of monogenic NDD cases.

Purpose of the Study:

• To provide a comprehensive longitudinal description of the developmental trajectories in individuals with RNU4-2 variants.
• To identify distinctive behavioral and neuropsychiatric hallmarks of ReNU syndrome.
• To explore neuroimaging findings and inform therapeutic strategies.

Main Methods:

• Case report of two patients with RNU4-2 variants, detailing developmental trajectories from infancy to adolescence.
• Comprehensive neuropsychiatric and adaptive functioning assessments.
• Neuroimaging analysis including white matter, corpus callosum, and ventricular structures.

Main Results:

• Both patients exhibited global developmental delay, impaired adaptive functioning, and language deficits.
• Persistent attention deficits and Autistic Spectrum Disorder were identified as key features.
• Neuroimaging revealed white matter reduction, corpus callosum thinning, and ventricular dysmorphisms.

Conclusions:

• RNU4-2-related disorder presents with distinct behavioral and neuropsychiatric features, including attention deficits and ASD.
• Early, individualized interventions focusing on communication and behavioral strategies are crucial.
• This study offers the first longitudinal characterization, aiding in optimizing patient management and outcomes.