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Copy number variation plays an important role in clinical epilepsy
Heather Olson1, Yiping Shen, Jennifer Avallone
1Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology and Neurogenetics Program, Department of Neurology, Boston Children's Hospital, and Harvard Medical School, Boston, MA.
Chromosomal microarray (CMA) testing detects copy number abnormalities that play a significant role in unexplained epilepsy. Implementing CMA in epilepsy evaluations can improve diagnosis rates.
Area of Science:
- Genetics
- Neurology
- Medical Diagnostics
Background:
- Epilepsy is a complex neurological disorder with various underlying causes.
- Copy number abnormalities (CNAs) are a known genetic factor contributing to neurological conditions.
Purpose of the Study:
- To evaluate the diagnostic utility of chromosomal microarray (CMA) testing for identifying CNAs in patients with epilepsy.
- To assess the role of CNAs in unexplained epilepsy cases.
Main Methods:
- Retrospective review of patients with epilepsy and CMA testing at a tertiary care center.
- Phenotypic characterization of patients with epilepsy-associated CNAs identified via CMA.
Main Results:
- Of 805 epilepsy patients, 323 (40%) had detectable CNVs, with 9% confirmed de novo.
- CNVs explained the epilepsy phenotype in at least 5% of cases, including epilepsy syndromes and variants in epilepsy genes.
- Recurrent CNVs, such as those involving Xp22.31, were frequently observed.
Conclusions:
- CNAs are important contributors to the epilepsy phenotype in a significant proportion of patients.
- The diagnostic yield of CMA for epilepsy is comparable to its yield in autism spectrum disorders and prenatal diagnosis.
- CMA testing is recommended for the evaluation of unexplained epilepsy.
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