Electro-clinical features in epileptic children with chromosome 15q duplication syndrome

M-T Dangles; V Malan; G Dumas; S Romana; O Raoul; D Coste-Zeitoun; C Soufflet; P Vignolo-Diard; N Bahi-Buisson; C Barnérias; N Chemaly; I Desguerre; C Gitiaux; M Hully; M Bourgeois; A Guimier; M Rio; A Munnich; R Nabbout; A Kaminska; M Eisermann

doi:10.1016/j.clinph.2021.02.010

Electro-clinical features in epileptic children with chromosome 15q duplication syndrome

Clin Neurophysiol. 2021 May;132(5):1126-1137. doi: 10.1016/j.clinph.2021.02.010. Epub 2021 Mar 10.

Authors

M-T Dangles¹, V Malan², G Dumas³, S Romana², O Raoul⁴, D Coste-Zeitoun⁵, C Soufflet⁶, P Vignolo-Diard⁶, N Bahi-Buisson⁷, C Barnérias⁸, N Chemaly⁹, I Desguerre⁷, C Gitiaux¹⁰, M Hully⁸, M Bourgeois¹¹, A Guimier¹², M Rio¹², A Munnich¹³, R Nabbout¹⁴, A Kaminska¹⁵, M Eisermann¹⁵

Affiliations

¹ Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Centre de Référence des Epilepsies Rares CRéER, Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France. Electronic address: marie-therese.dangles@aphp.fr.
² Université de Paris, Paris, France; Department of Cytogenetics, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
³ Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, Paris, France; Department of Psychiatry, Université de Montreal, CHU Sainte-Justine Hospital, Montreal, QC, Canada.
⁴ Department of Cytogenetics, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
⁵ Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Centre de Référence des Epilepsies Rares CRéER, Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
⁶ Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
⁷ Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France.
⁸ Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
⁹ Centre de Référence des Epilepsies Rares CRéER, Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
¹⁰ Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France.
¹¹ Department of Pediatric Neurosurgery, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
¹² Department of Genetics, Necker-Enfants Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
¹³ Université de Paris, Paris, France; Department of Genetics, Necker-Enfants Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France.
¹⁴ Centre de Référence des Epilepsies Rares CRéER, Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Department of Pediatric Neurology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France.
¹⁵ Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, Assistance Publique -Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France.

PMID: 33773177
DOI: 10.1016/j.clinph.2021.02.010

Abstract

Objective: We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15).

Methods: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.o to 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis.

Results: Seventy video-EEGs were analyzed (1-16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15 (8 m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7 m.o to 12 y.o, median 15 m). Epilepsy: 6 West syndrome (WS) (2intdup15, 4idic15); 4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-band rapid-rhythms (RR): present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age.

Conclusion: WS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay.

Significance: This study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.

Keywords: 15q11q13; Dup15q; EEG; Interstitial chromosome 15q; Inv dup 15; Isodicentric chromosome 15q.

MeSH terms

Adolescent
Beta Rhythm*
Child
Child, Preschool
Chromosome Aberrations
Chromosome Disorders / physiopathology*
Chromosomes, Human, Pair 15
Epilepsy / genetics
Epilepsy / physiopathology*
Female
Humans
Infant
Intellectual Disability / physiopathology*
Male
Sleep
Trisomy / physiopathology*
Wakefulness

Supplementary concepts

Duplication 15q11-q13 Syndrome
Partial Duplication 15q Syndrome