Pathogenic variants in PIGG (phosphatidylinositol glycan anchor biosynthesis, class G) disrupt glycosylphosphatidylinositol (GPI) anchoring of cell-surface proteins. Recently, biallelic PIGG variants have been linked to motor neuropathy with conduction block and temporal dispersion, suggesting a role for defective GPI anchoring in peripheral nerve function. We describe a 27-year-old woman carrying a homozygous nonsense variant in PIGG, c.1515G>A (p.Trp505*), presenting with continuous lower limb myokymia, gait ataxia, tremor and distal weakness since early adolescence. Electrophysiological evaluation revealed widespread myokymic discharges on electromyography, consistent with peripheral nerve hyperexcitability, and a pure motor polyneuropathy with temporal dispersion. This case report expands the clinical spectrum of PIGG-related disorders by identifying peripheral nerve hyperexcitability as a defining feature. The potential mechanistic link between defective GPI anchoring and neuronal hyperexcitability mediated through impaired function of GPI-anchored proteins such as contactin-1 and contactin-2 offers a compelling hypothesis connecting peripheral neuropathy, hyperexcitability, and cerebellar dysfunction.
Sampaio et al. (Thu,) studied this question.