Dravet-like syndrome with PCDH19 mutations in Taiwan - A multicenter study

Area of Science:

• Genetics
• Neurology
• Epilepsy Syndromes

Background:

• Protocadherin-19 (PCDH19) epilepsy is a rare, X-linked epilepsy syndrome primarily affecting females, characterized by early-onset seizures and developmental delay.
• Mutations in the PCDH19 gene are implicated, and some SCN1A-negative patients with Dravet-like epilepsy may harbor PCDH19 mutations.

Purpose of the Study:

• To characterize the clinical phenotype of patients with PCDH19 epilepsy in Taiwan.
• To analyze the relationship between PCDH19 mutations, antiseizure medications, brain imaging findings, and mutation types.

Main Methods:

• Retrospective review of medical records from July 2017 to December 2021.
• Analysis of clinical data and genetic reports from fifteen female patients diagnosed with PCDH19 epilepsy.

Main Results:

• Fifteen female patients (age 3-23) experienced seizure onset between 4 months and 2 years 7 months, with clustered generalized tonic-clonic or focal seizures.
• Intellectual disability varied, with 3 patients showing no impairment. Two patients had abnormal brain imaging. Patients received an average of 4 antiseizure medications (range 3-6).
• Missense and truncating variants comprised 40% and 46.7% of mutations, respectively. Most mutations were in the EC1-EC4 domains.

Conclusions:

• PCDH19 epilepsy exhibits distinct phenotypes and an X-linked expression pattern in females, often including psychiatric and behavioral issues.
• A wide range of antiseizure medications are used, with no specific class proving superior. No strong genotype-phenotype correlations were identified in this cohort.