Phenotypic Characterization of Five Children With PACS1-NDD: Longitudinal Insights Into Development, Behavior, and...

Area of Science:

• Neuroscience
• Genetics
• Developmental Pediatrics

Background:

• PACS1 neurodevelopmental disorder (PACS1-NDD), or Schuurs-Hoeijmakers syndrome, is a rare genetic condition linked to de novo mutations in the PACS1 gene.
• Previous reports suggest autistic traits in PACS1-NDD, but systematic longitudinal data are absent, necessitating further investigation.

Purpose of the Study:

• To provide the first longitudinal, multimodal characterization of neurodevelopmental trajectories in children with PACS1-NDD.
• To compare developmental profiles of children with PACS1-NDD to autistic and typically developing children.

Main Methods:

• Longitudinal follow-up of five children with genetically confirmed PACS1-NDD over 2-3.5 years using standardized behavioral, cognitive, and eye-tracking assessments.
• Structural MRI scans were acquired, and data were compared to a large cohort of autistic and typically developing children.

Main Results:

• Children with PACS1-NDD exhibited global developmental delays with heterogeneous trajectories, overlapping communication profiles with autistic children, and more pronounced motor impairments.
• All participants displayed autistic traits, with elevated restricted/repetitive behaviors and milder social-communication difficulties; pragmatic language skills were relatively preserved.
• Eye-tracking indicated preserved social interest but reduced gaze typicality, while MRI revealed globally reduced gray and white matter volumes.

Conclusions:

• This study offers the first comprehensive longitudinal characterization of PACS1-NDD, revealing distinct developmental patterns.
• Findings inform clinical management and identify potential outcome measures for future therapeutic trials in PACS1-NDD.
• Larger studies are needed to validate and expand upon these initial findings for PACS1-NDD.