Visual Evoked Potential Abnormalities in Phelan-McDermid Syndrome

Area of Science:

• Neuroscience
• Genetics
• Developmental Pediatrics

Background:

• Phelan-McDermid syndrome (PMS) is a genetic disorder caused by SHANK3 gene haploinsufficiency, leading to autism spectrum disorder (ASD) and intellectual disability.
• Understanding the neurobiological underpinnings of PMS is crucial for developing effective interventions.

Purpose of the Study:

• To investigate excitatory and inhibitory postsynaptic activity in children with PMS using visual evoked potentials (VEPs).
• To explore the association between VEP findings and genetic factors, specifically deletion size, in PMS.
• To assess the utility of VEPs as a noninvasive measure for clinical trials in PMS and ASD.

Main Methods:

• Transient VEPs were recorded from 175 children, including those with PMS, idiopathic ASD, typically developing controls, and unaffected siblings.
• Stimuli included standard and short-duration contrast-reversing checkerboard patterns.
• Test-retest reliability and correlations between VEP measures and deletion size were analyzed in the PMS group.

Main Results:

• Children with PMS and idiopathic ASD showed significantly smaller VEP amplitudes and reduced beta/gamma band activity compared to controls.
• High reliability was observed between standard and short-duration VEP conditions, and strong test-retest reliability was found in the PMS group.
• Deletion size in PMS was significantly correlated with P60-N75 VEP amplitude.

Conclusions:

• Distinct VEP waveform abnormalities in PMS suggest potential glutamatergic deficits linked to deletion size.
• Similar VEP patterns were observed in a subset of children with idiopathic ASD.
• VEPs provide a promising noninvasive tool for patient stratification and surrogate endpoints in PMS and ASD clinical trials.