A Novel Phenotypic Presentation of Absence Seizures in a 15-Month-Old with PIGK-Related GPI Biosynthesis Disorder: A...

PIGK-related glycosylphosphatidylinositol (GPI) biosynthesis disorder is an extremely rare neurodevelopmental condition, with only 12 cases described to date. It is caused by biallelic mutations in the PIGK gene, which encodes a catalytic subunit of the GPI transamidase complex. This enzyme facilitates the attachment of GPI anchors to proteins crucial for cellular signaling and development. Eight of the 12 described cases were reported to have seizures, but the electroclinical characteristics are not well defined.

We report a 15-month-old female who presented with global developmental delay, hypotonia, oral dysphagia, nystagmus, and cerebellar atrophy on MRI. Abnormal movements occurred at 10 months of age with intermittent, brief right arm tremors initially presumed to be benign myoclonus of infancy. However, subsequent 24-h video EEG revealed classic 3-Hz generalized spike-and-wave discharges with clinical correlates of behavioral arrest previously unrecognized, confirming a diagnosis of absence seizures - a feature not previously reported in the literature for PIGK-related disorders. Whole exome sequencing confirmed biallelic PIGK pathogenic variants. To our knowledge, this is the first reported case of typical absence seizures with 3-Hz generalized spike-and-wave discharges in a very young patient with confirmed PIGK mutation. Our report expands the known electroclinical phenotype of GPI-anchor deficiencies, suggesting the need to screen for subtle generalized epilepsy syndromes like absence, among affected infants.

This case highlights a novel EEG phenotype in PIGK-related GPI biosynthesis disorder underscoring the relevance of early EEG evaluation in infants with this extremely uncommon neurogenetic disorder.