Epilepsy in Rett syndrome - Lessons from the Rett networked database

Andreea Nissenkorn, Rachel S. Levy-Drummer, Ori Bondi, Alessandra Renieri, Laurent Villard, Francesca Mari, Maria A. Mencarelli, Caterina Lo Rizzo, Ilaria Meloni, Mercedes Pineda, Judith Armstrong, Angus Clarke, Nadia Bahi-Buisson, Bosnjak Vlatka Mejaski, Milena Djuric, Dana Craiu, Alexsandra Djukic, Giorgio Pini, Anne Marie Bisgaard, B. Melegh & 6 others Aglaia Vignoli, Silvia Russo, Cristina Anghelescu, Edvige Veneselli, Joussef Hayek, Bruria Ben-Zeev

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Summary Objective Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 ± (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p <0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR] 2.46, confidence interval [CI] 95% 1.3-4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy (OR 2.07, CI 95% 1.2-3.59) as well as for severe epilepsy (OR 3.4, CI 95% 1.6-7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy (OR 3.09 and 2.69, CI 95% 1.48-6.4 and 1.19-6.05, respectively), but not for epilepsy occurrence. Significance Various mutations in the MECP2 gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site-specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome.

Original languageEnglish
Pages (from-to)569-576
Number of pages8
JournalEpilepsia
Volume56
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Rett Syndrome
Epilepsy
Databases
Mutation
Odds Ratio
Age of Onset
Confidence Intervals
Seizures
Hand
Phenotype
Kaplan-Meier Estimate
Genetic Association Studies

Keywords

  • Database
  • MECP2
  • Preserved speech variant
  • Seizure

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Nissenkorn, A., Levy-Drummer, R. S., Bondi, O., Renieri, A., Villard, L., Mari, F., ... Ben-Zeev, B. (2015). Epilepsy in Rett syndrome - Lessons from the Rett networked database. Epilepsia, 56(4), 569-576. https://doi.org/10.1111/epi.12941

Epilepsy in Rett syndrome - Lessons from the Rett networked database. / Nissenkorn, Andreea; Levy-Drummer, Rachel S.; Bondi, Ori; Renieri, Alessandra; Villard, Laurent; Mari, Francesca; Mencarelli, Maria A.; Lo Rizzo, Caterina; Meloni, Ilaria; Pineda, Mercedes; Armstrong, Judith; Clarke, Angus; Bahi-Buisson, Nadia; Mejaski, Bosnjak Vlatka; Djuric, Milena; Craiu, Dana; Djukic, Alexsandra; Pini, Giorgio; Bisgaard, Anne Marie; Melegh, B.; Vignoli, Aglaia; Russo, Silvia; Anghelescu, Cristina; Veneselli, Edvige; Hayek, Joussef; Ben-Zeev, Bruria.

In: Epilepsia, Vol. 56, No. 4, 01.04.2015, p. 569-576.

Research output: Contribution to journalArticle

Nissenkorn, A, Levy-Drummer, RS, Bondi, O, Renieri, A, Villard, L, Mari, F, Mencarelli, MA, Lo Rizzo, C, Meloni, I, Pineda, M, Armstrong, J, Clarke, A, Bahi-Buisson, N, Mejaski, BV, Djuric, M, Craiu, D, Djukic, A, Pini, G, Bisgaard, AM, Melegh, B, Vignoli, A, Russo, S, Anghelescu, C, Veneselli, E, Hayek, J & Ben-Zeev, B 2015, 'Epilepsy in Rett syndrome - Lessons from the Rett networked database', Epilepsia, vol. 56, no. 4, pp. 569-576. https://doi.org/10.1111/epi.12941
Nissenkorn A, Levy-Drummer RS, Bondi O, Renieri A, Villard L, Mari F et al. Epilepsy in Rett syndrome - Lessons from the Rett networked database. Epilepsia. 2015 Apr 1;56(4):569-576. https://doi.org/10.1111/epi.12941
Nissenkorn, Andreea ; Levy-Drummer, Rachel S. ; Bondi, Ori ; Renieri, Alessandra ; Villard, Laurent ; Mari, Francesca ; Mencarelli, Maria A. ; Lo Rizzo, Caterina ; Meloni, Ilaria ; Pineda, Mercedes ; Armstrong, Judith ; Clarke, Angus ; Bahi-Buisson, Nadia ; Mejaski, Bosnjak Vlatka ; Djuric, Milena ; Craiu, Dana ; Djukic, Alexsandra ; Pini, Giorgio ; Bisgaard, Anne Marie ; Melegh, B. ; Vignoli, Aglaia ; Russo, Silvia ; Anghelescu, Cristina ; Veneselli, Edvige ; Hayek, Joussef ; Ben-Zeev, Bruria. / Epilepsy in Rett syndrome - Lessons from the Rett networked database. In: Epilepsia. 2015 ; Vol. 56, No. 4. pp. 569-576.
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title = "Epilepsy in Rett syndrome - Lessons from the Rett networked database",
abstract = "Summary Objective Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results Epilepsy was present in 68.1{\%} of the patients, with uncontrolled seizures in 32.6{\%} of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 ± (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p <0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR] 2.46, confidence interval [CI] 95{\%} 1.3-4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy (OR 2.07, CI 95{\%} 1.2-3.59) as well as for severe epilepsy (OR 3.4, CI 95{\%} 1.6-7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy (OR 3.09 and 2.69, CI 95{\%} 1.48-6.4 and 1.19-6.05, respectively), but not for epilepsy occurrence. Significance Various mutations in the MECP2 gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site-specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome.",
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T1 - Epilepsy in Rett syndrome - Lessons from the Rett networked database

AU - Nissenkorn, Andreea

AU - Levy-Drummer, Rachel S.

AU - Bondi, Ori

AU - Renieri, Alessandra

AU - Villard, Laurent

AU - Mari, Francesca

AU - Mencarelli, Maria A.

AU - Lo Rizzo, Caterina

AU - Meloni, Ilaria

AU - Pineda, Mercedes

AU - Armstrong, Judith

AU - Clarke, Angus

AU - Bahi-Buisson, Nadia

AU - Mejaski, Bosnjak Vlatka

AU - Djuric, Milena

AU - Craiu, Dana

AU - Djukic, Alexsandra

AU - Pini, Giorgio

AU - Bisgaard, Anne Marie

AU - Melegh, B.

AU - Vignoli, Aglaia

AU - Russo, Silvia

AU - Anghelescu, Cristina

AU - Veneselli, Edvige

AU - Hayek, Joussef

AU - Ben-Zeev, Bruria

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Summary Objective Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 ± (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p <0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR] 2.46, confidence interval [CI] 95% 1.3-4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy (OR 2.07, CI 95% 1.2-3.59) as well as for severe epilepsy (OR 3.4, CI 95% 1.6-7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy (OR 3.09 and 2.69, CI 95% 1.48-6.4 and 1.19-6.05, respectively), but not for epilepsy occurrence. Significance Various mutations in the MECP2 gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site-specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome.

AB - Summary Objective Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 ± (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p <0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR] 2.46, confidence interval [CI] 95% 1.3-4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy (OR 2.07, CI 95% 1.2-3.59) as well as for severe epilepsy (OR 3.4, CI 95% 1.6-7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy (OR 3.09 and 2.69, CI 95% 1.48-6.4 and 1.19-6.05, respectively), but not for epilepsy occurrence. Significance Various mutations in the MECP2 gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site-specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome.

KW - Database

KW - MECP2

KW - Preserved speech variant

KW - Seizure

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