Fever-Induced Paroxysmal Weakness and Encephalopathy, a New Phenotype of ATP1A3 Mutation
| Autor: | Sho T. Yano, Suzanne D. DeBrosse, Kenneth Silver, Richard Young, Kathryn J. Swoboda, Gyula Acsadi, Roseànne S. Ebel |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Ataxia Fever Encephalopathy Audiology Gastroenterology Apraxia 03 medical and health sciences 0302 clinical medicine Atrophy Developmental Neuroscience Internal medicine ATP1A3 medicine Humans Child Dystonia Family Health Brain Diseases Muscle Weakness Cerebellar ataxia business.industry Alternating hemiplegia of childhood medicine.disease 030104 developmental biology Phenotype Neurology Pediatrics Perinatology and Child Health Mutation Female Neurology (clinical) medicine.symptom Sodium-Potassium-Exchanging ATPase business 030217 neurology & neurosurgery |
| Zdroj: | Pediatric neurology. 73 |
| ISSN: | 1873-5150 |
| Popis: | Background We identified a group of patients with ATP1A3 mutations at residue 756 who display a new phenotype, distinct from alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndromes. Methods Four patients with c.2267G>A (R756H) mutations from two families and two patients with c.2267G>T (R756L) mutations from one family are described and compared with the previously reported patients with mutations resulting in R756H and R756C protein variants. Results Patients with ATP1A3 R756H have onset in childhood of infrequent, fever-triggered paroxysms of encephalopathy and weakness with slowly improving but persistent deficits. Motor findings of weakness are mostly generalized, and patients may also have bulbar or oculomotor problems. Longer-term outcomes range from mild motor apraxia with near-normal function to persistent dysphagia, dysarthria, cognitive deficit, motor apraxia, and inability to walk because of ataxia. Patients with ATP1A3 R756L have a similar phenotype that includes paroxysmal, stepwise progression of ataxia associated with infections. Conclusions ATP1A3 mutations affecting residue 756 result in a clinical syndrome, separate from those associated with previously described ATP1A3 mutations, which consists chiefly of fever-induced paroxysmal weakness and encephalopathy (FIPWE). Patients with R756L and R756C protein variants display more prominent ataxia, overlapping with the relapsing encephalopathy with cerebellar ataxia syndrome previously described in a patient with the c.2266C>T (R756C) mutation. All patients reported with mutations at residue 756 to date have had a similar episodic course and clinical features. Patients with mutations of ATP1A3 residue 756 appear to have a distinct clinical phenotype compared with patients with other ATP1A3 mutations, with fever-induced encephalopathy as key differentiating feature. |
| Databáze: | OpenAIRE |
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