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Neuropediatrics 2019; 50(06): 378-381
DOI: 10.1055/s-0039-1693143
Resident & Fellow Section: Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Cleft Palate as Distinguishing Feature in a Patient with GABRB3 Epileptic Encephalopathy

Daniel Bamborschke
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
,
Matthias Pergande
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
,
Hülya Sevcan Daimagüler
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
,
Elisabeth Mangold
3   Institute of Human Genetics, University of Bonn, Bonn, Germany
,
Jörg Dötsch
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
,
Peter Herkenrath
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
,
Sebahattin Cirak‡   *
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
2   Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
,
Walid Fazeli   *
1   Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
4   Institute for Molecular and Behavioral Neuroscience, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
› Author Affiliations
Further Information

Publication History

31 October 2018

04 April 2019

Publication Date:
18 July 2019 (online)

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Abstract

Mutations in GABAA-receptor subunit genes are associated with a heterogeneous spectrum of epilepsies. Patients with epilepsy caused by mutations in a specific GABAA-receptor (GABRA3) occasionally present with orofacial dysmorphism (e.g., cleft palates). While cleft palates have been described in Gabrb3 knockout mice and in humans with GABRB3 variants without epilepsy, the specific combination of epilepsy and cleft palate in humans with GABRB3 mutations has not yet been reported.

We describe a patient with epileptic encephalopathy (EE) who presented with therapy-refractory neonatal-onset myoclonic seizures and severe developmental delay. Electroencephalogram showed burst suppression pattern at neonatal age and hypsarrhythmia at infantile age. Initial magnetic resonance imaging was unremarkable. As he additionally presented with a cleft palate, we were curious whether cleft palate and EE had the same genetic origin. Whole exome sequencing of the index patient revealed a novel pathogenic heterozygous de novo mutation in GABRB3 (c.899T > C; p.I300T). In consistency with Gabrb3 knockout mice data, this is the first report of cleft palate in a patient with GABRB3 associated EE.

We suggest to add cleft palate to the phenotypic GABRB3 spectrum and to screen for mutations in GABAA-receptors in patients with EE and orofacial dysmorphism.

Keywords

GABRB3 - GABAA-receptor - epilepsy - cleft palate

* These are the shared last authors.