Format

Send to

Choose Destination
Pediatr Neurol. 2017 Aug;73:101-105. doi: 10.1016/j.pediatrneurol.2017.04.022. Epub 2017 Apr 29.

Fever-Induced Paroxysmal Weakness and Encephalopathy, a New Phenotype of ATP1A3 Mutation.

Author information

1
Section of Pediatric Neurology, Comer Children's Hospital, University of Chicago, Chicago, Illinois. Electronic address: sho.yano@uchospitals.edu.
2
Section of Pediatric Neurology, Comer Children's Hospital, University of Chicago, Chicago, Illinois.
3
Pediatric Neurology, Connecticut Children's Medical Center, University of Connecticut, Hartford, Connecticut.
4
Department of Genetics and Genome Sciences, Center for Human Genetics, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio.
5
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Abstract

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.

KEYWORDS:

ATP1A3; dystonia; episodic encephalopathy; genetics; pediatric

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center