Three novel patients with epileptic encephalopathy due to biallelic mutations in the PLCB1 gene

Area of Science:

• Genetics
• Neuroscience
• Pediatrics

Background:

• Biallelic mutations in the PLCB1 gene are associated with infantile epileptic encephalopathy.
• Phospholipase C beta 1 (PLCB1) is crucial for brain development.
• Only four cases were previously reported, limiting understanding of the disorder.

Purpose of the Study:

• To report three new patients with PLCB1-related encephalopathy.
• To further delineate the clinical, genetic, and electroencephalographic features of this rare condition.
• To expand the known spectrum of PLCB1 mutations and their phenotypic consequences.

Main Methods:

• Clinical case reporting of three patients with PLCB1 mutations.
• Genetic analysis including intragenic deletion and nonsense variant identification.
• Phenotypic characterization including neurological examination, developmental assessment, EEG, and neuroimaging.

Main Results:

• Three new patients identified: one sporadic with homozygous deletion, two cousins with homozygous p.(Arg222*) nonsense variant in PLCB1.
• All patients presented with severe to profound intellectual disability and infantile epileptic spasms (3-5 months).
• Other features included developmental arrest/regression, diverse seizure types, drug-resistant epilepsy, truncal hypotonia, and microcephaly (inconstant).

Conclusions:

• PLCB1-related encephalopathy is an extremely rare disorder with a narrow phenotypic spectrum.
• Key features include infantile spasms and severe to profound intellectual disability.
• The condition, while severe, may not present as a distinct recognizable clinical entity.