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Neuropediatrics 2021; 52(02): 109-122
DOI: 10.1055/s-0041-1722878
Original Article

Epilepsy in Nicolaides–Baraitser Syndrome: Review of Literature and Report of 25 Patients Focusing on Treatment Aspects

Benedikt Hofmeister
1   Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Technical University of Munich, Bogenhausen Academic Teaching Hospital, Munich, Germany
,
Celina von Stülpnagel
2   Institute for Transition, Rehabilitation and Palliation, Paracelsus Private Medical University of Salzburg, Salzburg, Austria
3   Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Comprehensive Epilepsy Program for Children, University Hospital Munich, Munich, Germany
,
Cornelia Betzler
2   Institute for Transition, Rehabilitation and Palliation, Paracelsus Private Medical University of Salzburg, Salzburg, Austria
4   Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany
,
Francesca Mari
5   Department of Medical Genetics, University of Siena, Sienna, Italy
,
Alessandra Renieri
5   Department of Medical Genetics, University of Siena, Sienna, Italy
,
Margherita Baldassarri
5   Department of Medical Genetics, University of Siena, Sienna, Italy
,
Edda Haberlandt
6   Department of Pediatrics, Krankenhaus der Stadt Dornbirn, Dornbirn, Austria
,
Katrien Jansen
7   Department of Development and Regeneration, University Hospitals of Leuven, Leuven, Belgium
,
Stefan Schilling
8   Department of Neuropediatrics, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany
,
Peter Weber
9   Department of Neuro- and Developmental Pediatrics, University Children’s Hospital Basel, Basel, Switzerland
,
Katja Ahlbory
10   Department of Neuropediatrics, Children’s Hospital Amsterdamer Straße, Kliniken Köln, Cologne, Germany
,
Shan Tang
11   Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom
,
Steffen Berweck
4   Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany
12   Department of Pediatrics, Ludwig Maximilian University of Munich, Munich, Germany
,
Gerhard Kluger
2   Institute for Transition, Rehabilitation and Palliation, Paracelsus Private Medical University of Salzburg, Salzburg, Austria
4   Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany
› Author Affiliations Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Abstract

Nicolaides–Baraitser syndrome (NCBRS), caused by a mutation in the SMARCA2 gene, which goes along with intellectual disability, congenital malformations, especially of face and limbs, and often difficult-to-treat epilepsy, is surveyed focusing on epilepsy and its treatment. Patients were recruited via “Network Therapy of Rare Epilepsies (NETRE)” and an international NCBRS parent support group. Inclusion criterion is NCBRS-defining SMARCA2 mutation. Clinical findings including epilepsy classification, anticonvulsive treatment, electroencephalogram (EEG) findings, and neurodevelopmental outcome were collected with an electronic questionnaire. Inclusion of 25 NCBRS patients with epilepsy in 23 of 25. Overall, 85% of the participants (17/20) reported generalized seizures, the semiology varied widely. EEG showed generalized epileptogenic abnormalities in 53% (9/17), cranial magnetic resonance imaging (cMRI) was mainly inconspicuous. The five most frequently used anticonvulsive drugs were valproic acid (VPA [12/20]), levetiracetam (LEV [12/20]), phenobarbital (PB [8/20]), topiramate (TPM [5/20]), and carbamazepine (CBZ [5/20]). LEV (9/12), PB (6/8), TPM (4/5), and VPA (9/12) reduced the seizures' frequency in more than 50%. Temporary freedom of seizures (>6 months) was reached with LEV (4/12), PB (3/8), TPM (1/5, only combined with PB and nitrazepam [NZP]), and VPA (4/12). Seizures aggravation was observed under lamotrigine (LTG [2/4]), LEV (1/12), PB (1/8), and VPA (1/12). Ketogenic diet (KD) and vagal nerve stimulation (VNS) reduced seizures' frequency in one of two each. This first worldwide retrospective analysis of anticonvulsive therapy in NCBRS helps to treat epilepsy in NCBRS that mostly shows only initial response to anticonvulsive therapy, especially with LEV and VPA, but very rarely shows complete freedom of seizures in this, rather genetic than structural epilepsy.

Keywords

Nicolaides–Baraitser syndrome - NCBRS - SMARCA2 - epilepsy - AED

Disclosure

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.




Publication History

Received: 16 July 2020

Accepted: 10 December 2020

Article published online:
12 February 2021

© 2021. Thieme. All rights reserved.

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