Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

Gianina Luca; José Haba-Rubio; Yves Dauvilliers; Gert-Jan Lammers; Sebastiaan Overeem; Claire E Donjacour; Geert Mayer; Sirous Javidi; Alex Iranzo; Joan Santamaria; Rosa Peraita-Adrados; Hyun Hor; Zoltan Kutalik; Giuseppe Plazzi; Francesca Poli; Fabio Pizza; Isabelle Arnulf; Michel Lecendreux; Claudio Bassetti; Johannes Mathis; Raphael Heinzer; Poul Jennum; Stine Knudsen; Peter Geisler; Aleksandra Wierzbicka; Eva Feketeova; Corinne Pfister; Ramin Khatami; Christian Baumann; Mehdi Tafti; European Narcolepsy Network

doi:10.1111/jsr.12044

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

Gianina Luca, José Haba-Rubio, Yves Dauvilliers, Gert-Jan Lammers, Sebastiaan Overeem, Claire E Donjacour, Geert Mayer, Sirous Javidi, Alex Iranzo, Joan Santamaria, Rosa Peraita-Adrados, Hyun Hor, Zoltan Kutalik, Giuseppe Plazzi, Francesca Poli, Fabio Pizza, Isabelle Arnulf, Michel Lecendreux, Claudio Bassetti, Johannes MathisRaphael Heinzer, Poul Jennum, Stine Knudsen, Peter Geisler, Aleksandra Wierzbicka, Eva Feketeova, Corinne Pfister, Ramin Khatami, Christian Baumann, Mehdi Tafti, European Narcolepsy Network

125 Citations (Scopus)

Abstract

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Original language	English
Journal	Journal of Sleep Research Online
Volume	22
Issue number	5
Pages (from-to)	482-495
Number of pages	14
ISSN	1365-2869
DOIs	https://doi.org/10.1111/jsr.12044
Publication status	Published - Oct 2013

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Luca, G., Haba-Rubio, J., Dauvilliers, Y., Lammers, G-J., Overeem, S., Donjacour, C. E., Mayer, G., Javidi, S., Iranzo, A., Santamaria, J., Peraita-Adrados, R., Hor, H., Kutalik, Z., Plazzi, G., Poli, F., Pizza, F., Arnulf, I., Lecendreux, M., Bassetti, C., ... Network, E. N. (2013). Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. Journal of Sleep Research Online, 22(5), 482-495. https://doi.org/10.1111/jsr.12044

Luca, G, Haba-Rubio, J, Dauvilliers, Y, Lammers, G-J, Overeem, S, Donjacour, CE, Mayer, G, Javidi, S, Iranzo, A, Santamaria, J, Peraita-Adrados, R, Hor, H, Kutalik, Z, Plazzi, G, Poli, F, Pizza, F, Arnulf, I, Lecendreux, M, Bassetti, C, Mathis, J, Heinzer, R, Jennum, P, Knudsen, S, Geisler, P, Wierzbicka, A, Feketeova, E, Pfister, C, Khatami, R, Baumann, C, Tafti, M & Network, EN 2013, 'Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study', Journal of Sleep Research Online, vol. 22, no. 5, pp. 482-495. https://doi.org/10.1111/jsr.12044

@article{e7af116320a84e2c8b2bf2984ed71ae0,

title = "Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study",

abstract = "The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.",

author = "Gianina Luca and Jos{\'e} Haba-Rubio and Yves Dauvilliers and Gert-Jan Lammers and Sebastiaan Overeem and Donjacour, {Claire E} and Geert Mayer and Sirous Javidi and Alex Iranzo and Joan Santamaria and Rosa Peraita-Adrados and Hyun Hor and Zoltan Kutalik and Giuseppe Plazzi and Francesca Poli and Fabio Pizza and Isabelle Arnulf and Michel Lecendreux and Claudio Bassetti and Johannes Mathis and Raphael Heinzer and Poul Jennum and Stine Knudsen and Peter Geisler and Aleksandra Wierzbicka and Eva Feketeova and Corinne Pfister and Ramin Khatami and Christian Baumann and Mehdi Tafti and Network, {European Narcolepsy}",

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journal = "Journal of Sleep Research",

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T1 - Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy

T2 - a European Narcolepsy Network study

AU - Luca, Gianina

AU - Haba-Rubio, José

AU - Dauvilliers, Yves

AU - Lammers, Gert-Jan

AU - Overeem, Sebastiaan

AU - Donjacour, Claire E

AU - Mayer, Geert

AU - Javidi, Sirous

AU - Iranzo, Alex

AU - Santamaria, Joan

AU - Peraita-Adrados, Rosa

AU - Hor, Hyun

AU - Kutalik, Zoltan

AU - Plazzi, Giuseppe

AU - Poli, Francesca

AU - Pizza, Fabio

AU - Arnulf, Isabelle

AU - Lecendreux, Michel

AU - Bassetti, Claudio

AU - Mathis, Johannes

AU - Heinzer, Raphael

AU - Jennum, Poul

AU - Knudsen, Stine

AU - Geisler, Peter

AU - Wierzbicka, Aleksandra

AU - Feketeova, Eva

AU - Pfister, Corinne

AU - Khatami, Ramin

AU - Baumann, Christian

AU - Tafti, Mehdi

AU - Network, European Narcolepsy

PY - 2013/10

Y1 - 2013/10

N2 - The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

AB - The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

U2 - 10.1111/jsr.12044

DO - 10.1111/jsr.12044

M3 - Journal article

C2 - 23496005

SN - 1365-2869

VL - 22

SP - 482

EP - 495

JO - Journal of Sleep Research

JF - Journal of Sleep Research

IS - 5

ER -

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

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