Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H

Autor: Edward C. Cooper, Sarah Weckhuysen, Sabine Grønborg, Maurizio Taglialatela, Yong-hui Jiang, Sarah B. Mulkey, John L. Carroll, Phillip L. Pearl, Rebecca C. Spillmann, Maria Roberta Cilio, Silvia Vieker, Kristen Park, Ingrid E. Scheffer, Nishtha Joshi, David A. Koolen, Megan L. Kelly, Bruria Ben-Zeev, Joost Nicolai, Mohamad A. Mikati
Přispěvatelé: Mulkey, Sarah B, Ben Zeev, Bruria, Nicolai, Joost, Carroll, John L, Grønborg, Sabine, Jiang, Yong Hui, Joshi, Nishtha, Kelly, Megan, Koolen, David A, Mikati, Mohamad A, Park, Kristen, Pearl, Phillip L, Scheffer, Ingrid E, Spillmann, Rebecca C, Taglialatela, Maurizio, Vieker, Silvia, Weckhuysen, Sarah, Cooper, Edward C, Cilio, Maria Roberta, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: FHML non-thematic output
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Myoclonus
Pediatrics
Electroencephalography
Epilepsy
0302 clinical medicine
Registries
POTASSIUM CHANNEL SUBUNITS
ONSET EPILEPTIC ENCEPHALOPATHY
KCNQ2
medicine.diagnostic_test
Infantile spasms
Epileptic encephalopathy
HYPEREXCITABILITY
Institutional review board
Magnetic Resonance Imaging
Epileptic spasms
Phenotype
Neurology
Anesthesia
Child
Preschool
Anticonvulsants
Female
medicine.symptom
Spasms
Infantile
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
medicine.medical_specialty
Encephalopathy
Arginine
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
VOLTAGE SENSOR
medicine
Humans
KCNQ2 Potassium Channel
Histidine
Cysteine
SUPPRESSION
SPECTRUM
Neonatal encephalopathy
business.industry
MUTATIONS
CONVULSIONS
Infant
Newborn
Infant
Neonatal seizures
medicine.disease
Respiration Disorders
030104 developmental biology
Respiratory failure
Infantile spasm
SEIZURES
Neurology (clinical)
Human medicine
business
030217 neurology & neurosurgery
Myoclonu
Zdroj: Epilepsia, 58, 436-445
Epilepsia
Epilepsia, 58(3), 436-445. Wiley
Epilepsia, 58, 3, pp. 436-445
ISSN: 0013-9580
Popis: Objective: To analyze whether KCNQ2 R201C and R201H variants, which show atypical gain-of-function electrophysiologic properties in vitro, have a distinct clinical presentation and outcome.Methods: Ten children with heterozygous, de novo KCNQ2 R201C or R201H variants were identified worldwide, using an institutional review board (IRB)-approved KCNQ2 patient registry and database. We reviewed medical records and, where possible, interviewed parents and treating physicians using a structured, detailed phenotype inventory focusing on the neonatal presentation and subsequent course.Results: Nine patients had encephalopathy from birth and presented with prominent startle-like myoclonus, which could be triggered by sound or touch. In seven patients, electroencephalography (EEG) was performed in the neonatal period and showed a burst-suppression pattern. However, myoclonus did not have an EEG correlate. In many patients the paroxysmal movements were misdiagnosed as seizures. Seven patients developed epileptic spasms in infancy. In all patients, EEG showed a slow background and multifocal epileptiform discharges later in life. Other prominent features included respiratory dysfunction (perinatal respiratory failure and/or chronic hypoventilation), hypomyelination, reduced brain volume, and profound developmental delay. One patient had a later onset, and sequencing indicated that a low abundance (similar to 20%) R201C variant had arisen by postzygotic mosaicism.Significance: Heterozygous KCNQ2 R201C and R201H gain-of-function variants present with profound neonatal encephalopathy in the absence of neonatal seizures. Neonates present with nonepileptic myoclonus that is often misdiagnosed and treated as seizures. Prognosis is poor. This clinical presentation is distinct from the phenotype associated with loss-of-function variants, supporting the value of in vitro functional screening. These findings suggest that gain-of-function and loss-of-function variants need different targeted therapeutic approaches.
Databáze: OpenAIRE
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