Abstracts

STXBP1-Encephalopathy in Adulthood: Focus on Seizures, Movement Disorders and Functional Independence

Abstract number : 2.31
Submission category : 12. Genetics / 12A. Human Studies
Year : 2021
Submission ID : 1826247
Source : www.aesnet.org
Presentation date : 12/9/2021 12:00:00 PM
Published date : Nov 22, 2021, 06:53 AM

Authors :
Hannah Stamberger, MD, PhD - Center for Molecular Neurology, University of Antwerp, VIB, Belgium; David Crosiers – Department of Neurology – Antwerp University Hospital, Antwerp, Belgium; Gana Balagura – IRCCS Istituto Giannina Gaslini", Genova, Italy; Anna Basu – Population Health Sciences Institute, New Castle University, Newcastle, United Kingdom; Claudia M. Bonardi – Department of Epilepsy Genetics – Danish Epilepsy Centre Filadelfia, Dianalund, Denmark; Gaetano Cantalupo – Child Neuropsychiatry Unit – University of Verona, Italy; Colin Ellis – Department of Neurology – University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Valentina Chiesa – Epilepsy Center, ASST Santi Paolo Carlo, Milano, Italy; Jacob Christensen – Department of Epilepsy Genetics – Danish Epilepsy Centre Filadelfia, Dianalund, Denmark.; Francesca Furia – Department of Epilepsy Genetics – Danish Epilepsy Centre Filadelfia, Dianalund, Denmark.; Fiona Gardiner – University of Melbourne, Austin Health, Melbourne, Victoria, Australia; Camille Giron – Department of Neurology – AP-HP, Pitié-Salpêtrière University Hospital, F-75013, Paris, France; Renzo Guerrini – Child Neurology Unit and Laboratories, Neuroscience Department – Children's Hospital A. Meyer - University of Florence, Florence, Italy; Karl Martin Klein – Departments of Clinical Neurosciences, Medical Genetics and Community Health Sciences – Hotchkiss Brain Institute & Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada; Christian Korff – Pediatric Neurology Unit – University Hospitals, Geneva, Switserland; Hana Krijtova – Department of Neurology – Second Faculty of Medicine, Charles University and Motol University Hospital Prague, Czech Republic; Melanie Leffner – The GOLD service, Waratah, NSW, Australia; Holger Lerche – Department of Neurology and Epileptology & Hertie Institute for Clinical Brain Research – University of Tubingen, Tubingen, Germany; Gaetan Lesca – Department of Medical Genetics – Lyon University Hospital, Université de Lyon, INMG, Lyon, France; David Lewis-Smith – Translational and Clinical Research Institute, Newcastle University, Newcastle, UK; Carla Marini – Child Neurology and Psychiatric Unit – G. Salesi Pediatric Hospital, United Hospitals of Ancona, Ancona, Italy; Laure Mazzola – Department of Neurology – University Hospital of St-Etienne, France; Sarah Mckeowns – Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA; Fanny Mochel – Department of Genetics – AP-HP, Pitié-Salpêtrière University Hospital, Reference Centers for Adult Neurometabolic diseases and Adult Leukodystrophies, F-75013, Paris, France; Francis Ramond – Service de Génétique – Centre Hospitalier Universitaire de Saint-Etienne, France; Philipp Reif – Department Of Neurology – Epilepsy Center Frankfurt Rhine-Main, Johann Wolfgang Goethe University, Frankfurt am Main, Germany; Aurélie Richard-Mornas – Unit of neurophysiology and epileptology – Hospices Civils of Lyon, Lyon, France; Felix Rosenow – Department of Neurology – Epilepsy Center Frankfurt Rhine-Main, Johann Wolfgang Goethe University, Frankfurt am Main, Germany; Christian Schropp – Kinderklinik Dritter Orden, Bischof-Altmann-Str.9, 94032 Passau, Germany; Rhys H. Thomas – Translational and Clinical Research Institute, Newcastle University, Newcastle, UK; Aglaia Vignoli – Child Neuropsychiatry Unit, Department of Health Sciences – ASST Santi Paolo e Carlo, San Paolo Hospital, Università Degli Studi di Milano, Milan, Italy; Yvonne Weber – Department of Epileptology and Neurology – University of Aachen, Aachen, Germany; Elizabeth Palmer – School of Women and Children's Health, Faculty of Medicine, UNSW, Randwick, Australia; Ingo Helbig – Division of Neurology – Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA; Ingrid E. Scheffer – University of Melbourne, Austin Health, Melbourne, Victoria, Australia; Pasquale Striano – IRCCS Istituto Giannina Gaslini", Genova, Italy; Rikke S. Møller – Department of Epilepsy Genetics – Danish Epilepsy Centre Filadelfia, Dianalund, Denmark; Elena Gardella – Department of Epilepsy Genetics – Danish Epilepsy Centre Filadelfia, Dianalund, Denmark; Sarah Weckhuysen – Applied and Translational Neurogenomics group – Center for Molecular Neurology, University of Antwerp, VIB, Belgium

Rationale: STXBP1-encephalopathy (STXBP1-E) is a severe early-onset developmental and epileptic encephalopathy (DEE). To date, no studies have systematically investigated the clinical presentation of STXBP1-E in adulthood. In this study, aimed to investigate the natural history of STXBP1-E in adults focusing on seizure evolution, presence of movement disorders and the level of functional (in)dependence.

Methods: Patients with a minimum age of 18 years carrying a (likely) pathogenic STXBP1 variant were included in the study. Treating clinicians were asked to complete clinical questionnaires and to perform semi-structured video examinations while performing tasks from the (modified) Unified Parkinson Disease Rating Scale when possible.

Results: 30 patients were included for summary statistics, with video recordings available for 19/30. Median age at last follow-up was 24 years (range 18-58 y). All patients had epilepsy, with median onset age 3.5 months. In one patients seizures started at adult age only. At last follow-up, 80% of adults had treatment resistant seizures despite long periods of seizure freedom in 38%. Tonic-clonic, focal and tonic seizures were the most frequent seizure types in adulthood. Of interest, epileptic spasms were still present in 3 adults. EEGs in adulthood most frequently showed focal or multifocal interictal epileptiform discharges in addition to generalised or focal slowing.

All patients had developmental delay with periods of regression in 58%, not always correlating with seizure activity. 87% had severe or profound intellectual disability, 42% had autistic features, and 62% significant behavioral problems. Video examinations showed gait disorders in all 12 patients able to walk including postural abnormalities with external rotation of the feet in 8, broad-based gait in 7, and asymmetric posture/dystonia in 4 patients. Tremor, present in 56%, was predominantly of the intentional/action type. Functional outcome concerning mobility was variable ranging from independent walking (50%) to complete wheelchair dependency (39%). 71% of adults were non-verbal and all were dependent on caregivers for most activities of daily living.

Conclusions: STXBP1-E warrants continuous monitoring for seizures in adult life. Epileptic spasms can continue into adulthood. Periods of regression are often present and can occur beyond early childhood. Movement disorders are frequent and involve multiple systems. While functional mobility is variable in adulthood, STXBP1-E generally leads to severe cognitive impairments with significant language problems and a high level of functional dependence. Understanding the natural history of STXBP1-E is important for genetic counseling and will inform future therapeutic trials.

Funding: Please list any funding that was received in support of this abstract.: /

Genetics