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Updated: Nov 1, 2025
A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Further delineation of PIGB-related early infantile epileptic encephalopathy
Silvia Schiavoni1, Carlotta Spagnoli1, Susanna Rizzi1
1Department of Pediatrics, Child Neurology Unit, Azienda USL- IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Insights
Pathogenic variants in the PIGB gene cause early infantile epileptic encephalopathy 80 (EIEE-80), a rare glycosylphosphatidylinositol deficiency. This study details a novel PIGB variant in a child with developmental delay and neuropathy, expanding knowledge of this ultra-rare disorder.
Area of Science:
- Genetics
- Neurology
- Biochemistry
Background:
- Pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class B (PIGB) gene were identified in 2019 as the cause of early infantile epileptic encephalopathy 80 (EIEE-80).
- EIEE-80 is an inherited disorder characterized by glycosylphosphatidylinositol (GPI) deficiency, presenting with a complex neurological phenotype including developmental delay, early-onset epilepsy, and peripheral neuropathy.
Observation:
- A 5-year-old girl from a consanguineous family presented with severe global developmental delay, absent speech, peripheral polyneuropathy, hypotonia, foot deformities, early-onset scoliosis, elevated serum alkaline phosphatase, and a single febrile status epilepticus episode.
- Brain MRI revealed hypomyelination.
- Whole-exome sequencing identified a likely pathogenic biallelic PIGB variant (NM_004855.4: c.463G>C, p.(Asp155His)).
Findings:
- The patient exhibited many characteristic clinical, neuroimaging, and laboratory findings associated with PIGB-related GPI deficiency.
- Notably, seizures were not a primary clinical manifestation in this patient, differentiating her presentation from previously described cases.
Implications:
- This case expands the clinical spectrum of PIGB-related disorders, highlighting that seizures may not be a dominant feature.
- Understanding the phenotypic variability of PIGB variants is crucial for accurate diagnosis and management of this ultra-rare genetic disorder.
- Further research into GPI deficiencies can elucidate complex biological pathways and inform therapeutic strategies.
Abstract:
Pathogenic variants in phosphatidylinositol glycan anchor biosynthesis class B (PIGB) gene have been first described as the cause of early infantile epileptic encephalopathy 80 (EIEE-80) in 2019. This disorder, an inherited glycosylphosphatidylinositol deficiency, is associated with a complex neurologic phenotype, including developmental delay, early-onset epilepsy and peripheral neuropathy. We report on a 5 year-old girl born from consanguineous parents, manifesting severe global developmental delay with absent speech, mixed peripheral polyneuropathy, hypotonia, bilateral equino-varo-supinated-cavus foot, early-onset scoliosis, elevated serum alkaline phosphatase and a single episode of febrile status epilepticus. Hypomyelination was documented on brain MRI. Whole-exome sequencing (WES) disclosed the likely pathogenic biallelic PIGB NM_004855.4: c.463G > C, p.(Asp155His) missense variant. In our patient, while other characteristic clinical, neuroimaging and laboratory findings (as described in the first research paper) were present, seizures were not a major clinical issue, thus contributing to our knowledge on this ultra-rare disorder.
