PRRT2 mutations: exploring the phenotypical boundaries

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene are associated with benign (familial) infantile convulsions (B(F)IC), infantile convulsions with choreoathetosis (ICCA), and paroxysmal dyskinesias (PDs).
• The role of PRRT2 mutations in other epilepsy syndromes remains unclear.
• A PRRT2 mutation was identified in a family with ICCA, including individuals with febrile seizures (FS) and West syndrome.

Purpose of the Study:

• To investigate the role of PRRT2 mutations in a diverse group of infantile epilepsy syndromes.
• To determine if PRRT2 mutations are causal in conditions beyond B(F)IC, ICCA, and PDs.

Main Methods:

• Screening of 460 patients with B(F)IC, ICCA, fever-related seizures, or infantile epileptic encephalopathies.
• Direct sequencing was used to test for point mutations in the PRRT2 gene.

Main Results:

• Heterozygous PRRT2 mutations were identified in 16 individuals (10 familial, 6 sporadic).
• All identified mutation carriers were diagnosed with B(F)IC, ICCA, or PD.
• No PRRT2 mutations were detected in other epilepsy syndromes.
• Some mutation carriers exhibited later-onset learning disabilities and impaired fine motor skills.

Conclusions:

• PRRT2 mutations are not implicated in the etiology of febrile seizures or infantile epileptic encephalopathies.
• B(F)IC, ICCA, and PD remain the primary phenotypes associated with PRRT2 mutations.
• Further clinical research is warranted to explore the developmental aspects, including learning disabilities and neuropsychiatric issues, in PRRT2 mutation carriers.