A Novel PIGG Variant Associated With Distal Hereditary Motor Neuropathy

BACKGROUND AND AIMS: To report a case of PIGG-related distal hereditary motor neuropathy (dHMN) associated with a novel missense variant and describe its clinical and electrodiagnostic features. METHODS: Case report with chart review. RESULTS: A 25-year-old woman with childhood-onset progressive distal motor impairment was evaluated for distal weakness without sensory loss. She had two isolated febrile seizures before 2 years of life but no developmental delay, intellectual disability, or learning difficulties. There were no other affected family members. Electrodiagnostic testing showed an axonal, distal motor-predominant neuropathy with conduction block. Brain MRI was normal. Trio whole-exome sequencing (WES) identified compound heterozygous PIGG variants: c.1515G>A, p.Trp505Ter (paternal) and c.2180G>A, p.Gly727Glu (maternal). INTERPRETATION: Biallelic PIGG variants were first described in severe multisystem GPI-anchor deficiency disorders and have subsequently been associated with milder motor neuropathy phenotypes, often accompanied by additional neurologic manifestations. This case further supports the emerging neuropathy-predominant spectrum of PIGG-related disease and demonstrates that dHMN with conduction block may occur with preserved neurodevelopment and relatively few additional neurologic manifestations. These findings support consideration of PIGG in the genetic evaluation of early-onset distal motor neuropathies.