Comprehensive Clinical Characteristics, Longitudinal Adaptive Functioning, and Electroencephalogram Activity in...

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• Mitogen-activated protein kinase 8-interacting protein 3 (MAPK8IP3) gene variants are linked to neurodevelopmental disorders.
• Understanding the clinical spectrum of MAPK8IP3-related NDD is crucial for diagnosis and management.

Purpose of the Study:

• To characterize the clinical features and genetic underpinnings of MAPK8IP3-related neurodevelopmental disorder.
• To investigate the correlation between variant types and symptom severity.

Main Methods:

• Retrospective analysis of 32 individuals with pathogenic/likely pathogenic MAPK8IP3 variants.
• Clinical assessment including motor function, cognitive scores (DAS-II), and neuroimaging (corpus callosum).
• Electroencephalogram (EEG) analysis to assess brain activity patterns.

Main Results:

• 32 individuals with heterozygous MAPK8IP3 variants (62.5% missense, 34.4% loss-of-function).
• Common symptoms: cognitive impairment, hypotonia, motor difficulties, strabismus, microcephaly, attention deficits. Corpus callosum thinning in 62.1%.
• Slower gait speed and wider base of support observed. Missense variants correlated with more severe clinical presentations than LOF variants.

Conclusions:

• MAPK8IP3-related NDD presents with a distinct set of neurodevelopmental and motor challenges.
• Genetic variants in MAPK8IP3, particularly missense types, significantly impact disease severity.
• Findings inform patient management strategies and lay groundwork for future therapeutic interventions.