Dados do Trabalho

Título

DNM1L MUTATION PRESENTING AS PROGRESSIVE MYOCLONIC EPILEPSY ASSOCIATED WITH ACUTE FEBRILE INFECTION-RELATED EPILEPSY SYNDROME

Apresentação do caso

A 12-year-old girl presented with recurrent tonic-clonic seizures, alternating with interictal sleepiness and confusion, after an initial picture of two days of fever and flu-like symptoms. The patient developed a refractory status epilepticus and was intubated and remained in coma for 30 days. The patient had a previous history of mild neurodevelopmental delay and a diagnosis of mild mental retardation. At seven years-old, the patient started to present tonic-clonic seizures, and later, the patient developed behavioral changes, an unbalanced gait, and sudden and brief jerks, consistent with eyelids myoclonus, multifocal erratic myoclonus and generalized myoclonus, that worsened with anxiety and with sound. At the examination the patient presented an ataxic gait, and mild dysmetria. During the investigation, an initial electroencephalogram showed generalized polyspikes and wave discharges, with bifrontal predominance. The brain magnetic resonance image showed cortical atrophy, subcortical vacuolar lesions in both cerebral hemispheres, and laminar cortical necrosis with underlying cortical thinning. Hematologic and then, anti-neuronal antibodies in cerebrospinal fluid (CSF) were normal. Thus, exome sequencing was performed, revealing a de novo pathogenic variant in DNM1L gene.

Discussão

The phenotypic spectrum of DNM1L mutation-related encephalopathy includes the presence of epileptic syndromes, as well as cognitive impairment, muscle hypotonia, dystonia and spasticity. Myoclonus and super refractory status epilepticus were reported in other studies and may represent a diagnostic clue.

Comentários finais

Although all described cases have some clinical peculiarities, there is a clinical pattern of great utility in diagnostic suspicion. Patients with mutation in DNM1L gene, may present in the form of a child or adolescent with variable clinical spectrum, ranging from a mild neuropsychomotor delay, often associated with myoclonus, that suddenly develops a refractory epileptic status, frequently having a fever or infection trigger. Iconic cases like these may be of great value, so that diagnosis can be made faster, and the appropriate treatment can be introduced as early as possible.

Referências (se houver)

[1] Wei Y and Qian M (2021) Case Report: A Novel de novo Mutation in DNM1L Presenting with Developmental Delay, Ataxia, and Peripheral Neuropathy. Front. Pediatr. 9:604105. doi: 10.3389/fped.2021.604105
[2] Ryan CS, Fine AL, Cohen AL, Schiltz BM, Renaud DL, Wirrell EC, Patterson MC, Boczek NJ, Liu R, Babovic-Vuksanovic D, Chan DC, Payne ET. De Novo DNM1L Variant in a Teenager with Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus. J Child Neurol. 2018 Sep;33(10):651-658.
[3] Ladds E, Whitney A, Dombi E, Hofer M, Anand G, Harrison V, Fratter C, Carver J, Barbosa IA, Simpson M, Jayawant S, Poulton J. De novo DNM1L mutation associated with mitochondrial epilepsy syndrome with fever sensitivity. Neurol Genet. 2018 Aug 2;4(4):e258.
[4] Schmid SJ, Wagner M, Goetz C, Makowski C, Freisinger P, Berweck S, Mall V, Burdach S, Juenger H. A De Novo Dominant Negative Mutation in DNM1L Causes Sudden Onset Status Epilepticus with Subsequent Epileptic Encephalopathy. Neuropediatrics. 2019 Jun;50(3):197-201.
[5] Fahrner JA, Liu R, Perry MS, Klein J, Chan DC. A novel de novo dominant negative mutation in DNM1L impairs mitochondrial fission and presents as childhood epileptic encephalopathy. Am J Med Genet A. 2016 Aug;170(8):2002-11.

Fonte de Fomento (se houver)

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