Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers *†‡Sarah Weckhuysen, *†Philip Holmgren, *†Rik Hendrickx, §¶Anna C. Jansen, §Daniele Hasaerts, §Charlotte Dielman, #Julitta de Bellescize, **††Nadia Boutry-Kryza, **††Gaetan Lesca, ‡‡Sarah Von Spiczak, ‡‡Ingo Helbig, §§Deepak Gill, ¶¶Simone Yendle, ##Rikke S. Møller, ##Laura Klitten, ***Christian Korff, †††Catherine Godfraind, ‡‡‡Kenou Van Rijckevorsel, *†§§§Peter De Jonghe, ¶¶¶###Helle Hjalgrim, ¶¶****††††Ingrid E. Scheffer, and *†Arvid Suls *Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; †Laboratory of Neurogenetics, Institute Born- Bunge, University of Antwerp, Antwerp, Belgium; ‡Epilepsy Center Kempenhaeghe, Oosterhout, The Netherlands; §Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium; ¶Department of Public Health, Vrije Universiteit Brussel, Brussels, Belgium; #Epilepsy, Sleep and Pediatric Neurophysiology, University Hospitals of Lyon (HCL), Lyon, France; **Department of Medical Genetics, Hospices Civils de Lyon, University Lyon 1, Lyon, France; ††TIGER Team, INSERM, U1028, CNRS UMR5292, Lyon Neuroscience Research Center, Lyon, France; ‡‡Department of Neuropediatrics, University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany; §§TY Nelson Department of Neurology, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia; ¶¶Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia; ##Danish Epilepsy Center, Dianalund, Denmark; ***Pediatric Neurology, Child and Adolescent Department, University Hospitals, Geneva, Switzerland; †††Laboratory of Pathology, University Hospital St-Luc, Catholic University of Louvain, Brussels, Belgium; ‡‡‡Reference Center for Refractory Epilepsy, University Hospital St Luc, Catholic University of Louvain, Brussels, Belgium; §§§Department of Neurology, University Hospital Antwerp, Antwerp, Belgium; ¶¶¶Wilhelm Johannsen Center for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark; ###Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark; ****Florey Neurosciences Institutes, Melbourne, Australia; and ††††Department of Paediatrics, Royal Children’s Hospital, University of Melbourne, Melbourne, Australia SUMMARY Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated. Therefore, we screened a cohort of 160 patients with an unexplained EE, including patients with early myoclonic encephalopathy (EME), Ohtahara syndrome, West syn- drome, nonsyndromic EE with onset in the first year, and Lennox-Gastaut syndrome (LGS). We found six de novo mutations in six patients presenting as Ohtahara syndrome (2/6, 33%), West syndrome (1/65, 2%), and nonsyndromic early onset EE (3/64, 5%). No mutations were found in LGS or EME. Only two of four mutation carriers with neonatal seizures had Ohtahara syndrome. Epileptic spasms were present in five of six patients. One patient with normal magnetic resonance imaging (MRI) but focal seizures underwent epilepsy surgery and seizure frequency dropped drastically. Neuropathology showed a focal cortical dyspla- sia type 1a. There is a need for additional neuropathologic studies to explore whether STXBP1 mutations can lead to structural brain abnormalities. KEY WORDS: Epileptic encephalopathy, Genetics, West syndrome, Ohtahara syndrome. The epileptic encephalopathies (EEs) are devastating disorders in which early onset severe epilepsy is associated with slowing or regression of development. For many patients the etiology remains unknown but the recent discovery of many new genes for EEs leads to the presump- tion that these cases may also have a genetic basis. The lack of an etiologic diagnosis entails additional uncertainties for parents concerning outcome and recurrence risk. Ongoing studies to unravel the genetics of EE are crucial to guide clinicians in genetic testing and counseling. Since 2008, STXBP1 mutations have been identified in patients with Ohtahara syndrome, West syndrome, and patients with early onset EE (Saitsu et al., 2008; Deprez et al., 2010). Many patients also present nonepileptic move- ment disorders (Mignot et al., 2011; Milh et al., 2011). Until now 37 patients with an STXBP1 mutation have been reported in the literature. By screening a large cohort of patients with EE we aimed to further define clinical features that warrant STXBP1 screening. In addition, given the Accepted January 17, 2013; Early View publication February 14, 2013. Address correspondence to Arvid Suls, VIB-Department of Molecular Genetics, Neurogenetics Group, University of Antwerp, Campus CDE, Parking P4, Building V, Universiteitsplein 1, 2610 Antwerp, Belgium. E-mail: arvid.suls@molgen.vib-ua.be Wiley Periodicals, Inc. © 2013 International League Against Epilepsy e74 Epilepsia, 54(5):e74–e80, 2013 doi: 10.1111/epi.12124 BRIEF COMMUNICATION