Visual Evoked Potential Abnormalities in Phelan-McDermid Syndrome

Abstract

Objective: The current study used visual evoked potentials (VEPs) to examine excitatory and inhibitory postsynaptic activity in children with Phelan-McDermid syndrome (PMS) and the association with genetic factors. PMS is caused by haploinsufficiency of SHANK3 on chromosome 22 and represents a common single-gene cause of autism spectrum disorder (ASD) and intellectual disability.

Method: Transient VEPs were obtained from 175 children, including 31 with PMS, 79 with idiopathic ASD, 45 typically developing controls, and 20 unaffected siblings of children with PMS. Stimuli included standard and short-duration contrast-reversing checkerboard conditions, and the reliability between these 2 conditions was assessed. Test-retest reliability and correlations with deletion size were explored in the group with PMS.

Results: Children with PMS and, to a lesser extent, those with idiopathic ASD displayed significantly smaller amplitudes and decreased beta and gamma band activity relative to TD controls and PMS siblings. Across groups, high intraclass correlation coefficients were obtained between standard and short-duration conditions. In children with PMS, test-retest reliability was strong. Deletion size was significantly correlated with P₆₀-N₇₅ amplitude for both conditions.

Conclusion: Children with PMS displayed distinct transient VEP waveform abnormalities in both time and frequency domains that might reflect underlying glutamatergic deficits that were associated with deletion size. A similar response pattern was observed in a subset of children with idiopathic ASD. VEPs offer a noninvasive measure of excitatory and inhibitory neurotransmission that holds promise for stratification and surrogate endpoints in ongoing clinical trials in PMS and ASD.

Keywords: Phelan-McDermid syndrome; autism spectrum disorder; transient VEP; visual evoked potential.

Figure 1.

Representative Transient Visual Evoked Potentials (VEP) Waveforms Note: (A) Representative transient VEP waveforms from a participant with PMS (blue), iASD (red), and a TD control (grey). (B) Mean amplitudes for the P₆₀-N₇₅ and N₇₅-P₁₀₀ tVEP components for the standard condition (top) and short condition (bottom). iASD (red) and PMS (blue) groups show reduced amplitudes compared to TD (grey) and PMS sibs (blue/grey striped). Errors bars represent 95% CI. iASD = idiopathic autism spectrum disorder; PMS = Phelan-McDermid syndrome; TD = typically developing; tVEP = transient visual evoked potential. *p< 0.05, **p< 0.01, ***p< 0.001.

Figure 2.

Frequency Band Activity by Group Note:PMS (blue) and iASD (red) groups show reduced MSC values across multiple frequency bands relative to TD (grey) and PMS sibs (blue/grey striped) groups in both the standard condition (left) and short condition (right). Errors bars represent 95% CI. iASD = idiopathic autism spectrum disorder; MSC = magnitude-squared coherence; PMS = Phelan-McDermid syndrome; TD = typically developing. *p< 0.05, **p< 0.01, ***p< 0.001.