Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients

Sarah Weckhuysen, Vanja Ivanovic, Rik Hendrickx, Rudy Van Coster, Helle Hjalgrim, Rikke S. Møller, Sabine Grønborg, An Sofie Schoonjans, Berten Ceulemans, Sinead B. Heavin, Christin Eltze, Rita Horvath, Gianluca Casara, Tiziana Pisano, Lucio Giordano, Kevin Rostasy, Edda Haberlandt, Beate Albrecht, Andrea Bevot, Ira BenkelSteffan Syrbe, Beth Sheidley, Renzo Guerrini, Annapurna Poduri, Johannes R. Lemke, Simone Mandelstam, Ingrid Scheffer, Marco Angriman, Pasquale Striano, Carla Marini, Arvid Suls, Peter De Jonghe

Research output: Contribution to journalArticle

Abstract

Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.

Original languageEnglish
Pages (from-to)1697-1703
Number of pages7
JournalNeurology
Volume81
Issue number19
DOIs
Publication statusPublished - Nov 5 2013

Fingerprint

Brain Diseases
Neuroimaging
Seizures
Mutation
Missense Mutation
Epilepsy
Genes
Carbamazepine
Apnea
Mutation Rate
Bradycardia
Sudden Death
Age of Onset
Intellectual Disability
Electroencephalography
Onset
Phenotype

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Weckhuysen, S., Ivanovic, V., Hendrickx, R., Van Coster, R., Hjalgrim, H., Møller, R. S., ... De Jonghe, P. (2013). Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients. Neurology, 81(19), 1697-1703. https://doi.org/10.1212/01.wnl.0000435296.72400.a1

Extending the KCNQ2 encephalopathy spectrum : Clinical and neuroimaging findings in 17 patients. / Weckhuysen, Sarah; Ivanovic, Vanja; Hendrickx, Rik; Van Coster, Rudy; Hjalgrim, Helle; Møller, Rikke S.; Grønborg, Sabine; Schoonjans, An Sofie; Ceulemans, Berten; Heavin, Sinead B.; Eltze, Christin; Horvath, Rita; Casara, Gianluca; Pisano, Tiziana; Giordano, Lucio; Rostasy, Kevin; Haberlandt, Edda; Albrecht, Beate; Bevot, Andrea; Benkel, Ira; Syrbe, Steffan; Sheidley, Beth; Guerrini, Renzo; Poduri, Annapurna; Lemke, Johannes R.; Mandelstam, Simone; Scheffer, Ingrid; Angriman, Marco; Striano, Pasquale; Marini, Carla; Suls, Arvid; De Jonghe, Peter.

In: Neurology, Vol. 81, No. 19, 05.11.2013, p. 1697-1703.

Research output: Contribution to journalArticle

Weckhuysen, S, Ivanovic, V, Hendrickx, R, Van Coster, R, Hjalgrim, H, Møller, RS, Grønborg, S, Schoonjans, AS, Ceulemans, B, Heavin, SB, Eltze, C, Horvath, R, Casara, G, Pisano, T, Giordano, L, Rostasy, K, Haberlandt, E, Albrecht, B, Bevot, A, Benkel, I, Syrbe, S, Sheidley, B, Guerrini, R, Poduri, A, Lemke, JR, Mandelstam, S, Scheffer, I, Angriman, M, Striano, P, Marini, C, Suls, A & De Jonghe, P 2013, 'Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients', Neurology, vol. 81, no. 19, pp. 1697-1703. https://doi.org/10.1212/01.wnl.0000435296.72400.a1
Weckhuysen S, Ivanovic V, Hendrickx R, Van Coster R, Hjalgrim H, Møller RS et al. Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients. Neurology. 2013 Nov 5;81(19):1697-1703. https://doi.org/10.1212/01.wnl.0000435296.72400.a1
Weckhuysen, Sarah ; Ivanovic, Vanja ; Hendrickx, Rik ; Van Coster, Rudy ; Hjalgrim, Helle ; Møller, Rikke S. ; Grønborg, Sabine ; Schoonjans, An Sofie ; Ceulemans, Berten ; Heavin, Sinead B. ; Eltze, Christin ; Horvath, Rita ; Casara, Gianluca ; Pisano, Tiziana ; Giordano, Lucio ; Rostasy, Kevin ; Haberlandt, Edda ; Albrecht, Beate ; Bevot, Andrea ; Benkel, Ira ; Syrbe, Steffan ; Sheidley, Beth ; Guerrini, Renzo ; Poduri, Annapurna ; Lemke, Johannes R. ; Mandelstam, Simone ; Scheffer, Ingrid ; Angriman, Marco ; Striano, Pasquale ; Marini, Carla ; Suls, Arvid ; De Jonghe, Peter. / Extending the KCNQ2 encephalopathy spectrum : Clinical and neuroimaging findings in 17 patients. In: Neurology. 2013 ; Vol. 81, No. 19. pp. 1697-1703.
@article{878ad7e5cc684e2fad195c44931d3e9a,
title = "Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients",
abstract = "Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13{\%}). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. Conclusion: KCNQ2 mutations cause approximately 13{\%} of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.",
author = "Sarah Weckhuysen and Vanja Ivanovic and Rik Hendrickx and {Van Coster}, Rudy and Helle Hjalgrim and M{\o}ller, {Rikke S.} and Sabine Gr{\o}nborg and Schoonjans, {An Sofie} and Berten Ceulemans and Heavin, {Sinead B.} and Christin Eltze and Rita Horvath and Gianluca Casara and Tiziana Pisano and Lucio Giordano and Kevin Rostasy and Edda Haberlandt and Beate Albrecht and Andrea Bevot and Ira Benkel and Steffan Syrbe and Beth Sheidley and Renzo Guerrini and Annapurna Poduri and Lemke, {Johannes R.} and Simone Mandelstam and Ingrid Scheffer and Marco Angriman and Pasquale Striano and Carla Marini and Arvid Suls and {De Jonghe}, Peter",
year = "2013",
month = "11",
day = "5",
doi = "10.1212/01.wnl.0000435296.72400.a1",
language = "English",
volume = "81",
pages = "1697--1703",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "19",

}

TY - JOUR

T1 - Extending the KCNQ2 encephalopathy spectrum

T2 - Clinical and neuroimaging findings in 17 patients

AU - Weckhuysen, Sarah

AU - Ivanovic, Vanja

AU - Hendrickx, Rik

AU - Van Coster, Rudy

AU - Hjalgrim, Helle

AU - Møller, Rikke S.

AU - Grønborg, Sabine

AU - Schoonjans, An Sofie

AU - Ceulemans, Berten

AU - Heavin, Sinead B.

AU - Eltze, Christin

AU - Horvath, Rita

AU - Casara, Gianluca

AU - Pisano, Tiziana

AU - Giordano, Lucio

AU - Rostasy, Kevin

AU - Haberlandt, Edda

AU - Albrecht, Beate

AU - Bevot, Andrea

AU - Benkel, Ira

AU - Syrbe, Steffan

AU - Sheidley, Beth

AU - Guerrini, Renzo

AU - Poduri, Annapurna

AU - Lemke, Johannes R.

AU - Mandelstam, Simone

AU - Scheffer, Ingrid

AU - Angriman, Marco

AU - Striano, Pasquale

AU - Marini, Carla

AU - Suls, Arvid

AU - De Jonghe, Peter

PY - 2013/11/5

Y1 - 2013/11/5

N2 - Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.

AB - Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.

UR - http://www.scopus.com/inward/record.url?scp=84888219819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888219819&partnerID=8YFLogxK

U2 - 10.1212/01.wnl.0000435296.72400.a1

DO - 10.1212/01.wnl.0000435296.72400.a1

M3 - Article

C2 - 24107868

AN - SCOPUS:84888219819

VL - 81

SP - 1697

EP - 1703

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 19

ER -