Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan;60(1):155-164.
doi: 10.1111/epi.14618. Epub 2018 Dec 7.

Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability

Francesca M Snoeijen-Schouwenaars  1 , Jans S van Ool  1 , Judith S Verhoeven  2 , Petra van Mierlo  2 , Hilde M H Braakman  2 , Eric E Smeets  3 , Joost Nicolai  2   4 , Jeroen Schoots  5 , Mariel W A Teunissen  6 , Rob P W Rouhl  4   6   7 , In Y Tan  1 , Helger G Yntema  5 , Han G Brunner  3   5 , Rolph Pfundt  5 , Alexander P Stegmann  3 , Erik-Jan Kamsteeg  5 , Helenius J Schelhaas  2 , Marjolein H Willemsen  3   5
Affiliations

Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability

Francesca M Snoeijen-Schouwenaars et al. Epilepsia. 2019 Jan.

Abstract

Objective: Epilepsy is highly prevalent among patients with intellectual disability (ID), and seizure control is often difficult. Identification of the underlying etiology in this patient group is important for daily clinical care. We assessed the diagnostic yield of whole exome sequencing (WES). In addition, we evaluated which clinical characteristics influence the likelihood of identifying a genetic cause and we assessed the potential impact of the genetic diagnosis on (antiepileptic) treatment strategy.

Methods: One hundred patients with both unexplained epilepsy and (borderline) ID (intelligence quotient ≤ 85) were included. All patients were evaluated by a clinical geneticist, a (pediatric) neurologist, and/or a specialist ID physician. WES analysis was performed in two steps. In step 1, analysis was restricted to the latest versions of ID and/or epilepsy gene panels. In step 2, exome analysis was extended to all genes (so-called full exome analysis). The results were classified according to the American College of Medical Genetics and Genomics guidelines.

Results: In 58 patients, the diagnostic WES analysis reported one or more variant(s). In 25 of the 100 patients, these were classified as (likely) pathogenic, in 24 patients as variants of uncertain significance, and in the remaining patients the variant was most likely not related to the phenotype. In 10 of 25 patients (40%) with a (likely) pathogenic variant, the genetic diagnosis might have an impact on the treatment strategy in the future.

Significance: This study illustrates the clinical diagnostic relevance of WES for patients with both epilepsy and ID. It also demonstrates that implementing WES diagnostics might have impact on the (antiepileptic) treatment strategy in this population. Confirmation of variants of uncertain significance in (candidate) genes may further increase the yield.

Keywords: genetic diagnosis; learning disability; next generation sequencing; seizures.

PubMed Disclaimer

Comment in