A De Novo Dominant Negative Mutation in DNM1L Causes Sudden Onset Status Epilepticus with Subsequent Epileptic Encephalopathy

S. J. Schmid; M. Wagner; C. Goetz; C. Makowski; P. Freisinger; S. Berweck; V. Mall; S. Burdach; H. Juenger

doi:10.1055/s-0039-1685217

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2019; 50(03): 197-201
DOI: 10.1055/s-0039-1685217

Short Communication

Georg Thieme Verlag KG Stuttgart · New York

A De Novo Dominant Negative Mutation in DNM1L Causes Sudden Onset Status Epilepticus with Subsequent Epileptic Encephalopathy

S. J. Schmid

¹Department of Pediatrics, Kinderklinik Muenchen Schwabing, Klinikum Schwabing, StKM GmbH und Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

M. Wagner

²Institute of Human Genetics, Technical University Munich, Munich, Germany

³Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

⁴Institut für Neurogenomik, Helmholtz Zentrum München, Neuherberg, Germany

,

C. Goetz

¹Department of Pediatrics, Kinderklinik Muenchen Schwabing, Klinikum Schwabing, StKM GmbH und Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

C. Makowski

¹Department of Pediatrics, Kinderklinik Muenchen Schwabing, Klinikum Schwabing, StKM GmbH und Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

P. Freisinger

⁵Department of Pediatrics, Klinikum Reutlingen, Reutlingen, Germany

,

S. Berweck

⁶Schoen Klinik Vogtareuth, Epilepsy Center for Children and Adolescents, Hospital for Neuropediatrics and Neurological Rehabilitation, Vogtareuth, Germany

⁷Dr. von Hauner Children's Hospital, Munich University, München, Germany

,

V. Mall

⁸Department of Social Pediatrics and Developmental Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany

,

S. Burdach

¹Department of Pediatrics, Kinderklinik Muenchen Schwabing, Klinikum Schwabing, StKM GmbH und Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

H. Juenger

¹Department of Pediatrics, Kinderklinik Muenchen Schwabing, Klinikum Schwabing, StKM GmbH und Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

› Institutsangaben

Abstract

Mitochondrial dynamics such as fission and fusion play a vital role in normal brain development and neuronal activity. DNM1L encodes a dynamin-related protein 1 (Drp1), which is a GTPase essential for proper mitochondrial fission. The clinical phenotype of DNM1L mutations depends on the degree of mitochondrial fission deficiency, ranging from severe encephalopathy and death shortly after birth to initially normal development and then sudden onset of refractory status epilepticus with very poor neurologic outcome. We describe a case of a previously healthy 3-year-old boy with a mild delay in speech development until the acute onset of a refractory status epilepticus with subsequent epileptic encephalopathy and very poor neurologic outcome. The de novo missense mutation in DNM1L (c.1207C > T, p.R403C), which we identified in this case, seems to determine a unique clinical course, strikingly similar to four previously described patients in literature with the identical de novo heterozygous missense mutation in DNM1L.

Keywords

epileptic encephalopathy - DNM1L - Drp1 - mitochondrial fission - status epilepticus - childhood epilepsy

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Referenzen

References
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