scholarly journals ATP1A3 Gene Mutation in Rapid Onset Dystonia Parkinsonism (RDP) And Alternating Hemiplegia of Childhood (AHC) Syndromes

2019 ◽  
Vol 2 (3) ◽  
Author(s):  
Behzad Saberi
Keyword(s):  
Gene Mutation ◽  
Rapid Onset ◽  
Alternating Hemiplegia Of Childhood ◽  
Atp1a3 Gene

Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity

2018 ◽  
Vol 49 (05) ◽  
pp. 342-346 ◽  
Author(s):  
Niklas Holze ◽  
Andreas Baalen ◽  
Ulrich Stephani ◽  
Ingo Helbig ◽  
Hiltrud Muhle
Keyword(s):  
Neurological Disorders ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Rapid Onset ◽  
Epileptic Activity ◽  
First Year ◽  
Pathogenic Variants ◽  
Alternating Hemiplegia Of Childhood ◽  
First Year Of Life ◽  
Atp1a3 Gene

AbstractMutations in the ATP1A3 gene are known to cause alternating hemiplegia of childhood (AHC) and rapid-onset dystonia parkinsonism (RDP). Both conditions are childhood-onset neurological disorders with distinct symptoms and different times of onset. ATP1A3 has also been associated with CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss). Within the various ATP1A3-related neurological syndromes, a specific genotype–phenotype correlation is starting to emerge. Several mutations such as the relatively common p.E815K pathogenic variant have been shown to strongly correlate with AHC, while others may cause both AHC and RDP. A significant subset of patients with AHC and RDP are reported to have epileptic seizures. Even though detailed clinical descriptions of seizures in childhood are rare, seizures involving apneic events seem to be frequent in ATP1A3-related neurological disorders. Here, we describe two children with unexplained severe apnea beginning around the first year of life and pathogenic variants in ATP1A3. We hypothesize that the symptoms are early-onset autonomic seizures related to the underlying pathogenic ATP1A3 variants.

scholarly journals RAPID-ONSET DYSTONIA-PARKINSONISM IN A CHILD WITH A NOVEL ATP1A3 GENE MUTATION

Neurology ◽  
2009 ◽  
Vol 73 (5) ◽  
pp. 400-401 ◽  
Author(s):  
I. A. Anselm ◽  
K. J. Sweadner ◽  
S. Gollamudi ◽  
L. J. Ozelius ◽  
B. T. Darras
Keyword(s):  
Gene Mutation ◽  
Rapid Onset ◽  
Atp1a3 Gene

Alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism: Phenotypic spectrum of ATP1A3-associated disorders

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
K Brockmann ◽  
H Rosewich ◽  
H Thiele ◽  
U Maschke ◽  
P Huppke ◽  
...  
Keyword(s):  
Rapid Onset ◽  
Alternating Hemiplegia Of Childhood ◽  
Phenotypic Spectrum

scholarly journals ATP1A3-Related Disorders: An Ever-Expanding Clinical Spectrum

2021 ◽  
Vol 12 ◽  
Author(s):  
Philippe A. Salles ◽  
Ignacio F. Mata ◽  
Tobias Brünger ◽  
Dennis Lal ◽  
Hubert H. Fernandez
Keyword(s):  
Original Description ◽  
Rapid Onset ◽  
Acute Onset ◽  
Clinical Spectrum ◽  
Pes Cavus ◽  
Sodium Potassium ◽  
Pathogenic Variants ◽  
Alternating Hemiplegia Of Childhood ◽  
The Central Nervous System ◽  
Neurological Features

The Na+/K+ ATPases are Sodium-Potassium exchanging pumps, with a heteromeric α-β-γ protein complex. The α3 isoform is required as a rescue pump, after repeated action potentials, with a distribution predominantly in neurons of the central nervous system. This isoform is encoded by the ATP1A3 gene. Pathogenic variants in this gene have been implicated in several phenotypes in the last decades. Carriers of pathogenic variants in this gene manifest neurological and non-neurological features in many combinations, usually with an acute onset and paroxysmal episodes triggered by fever or other factors. The first three syndromes described were: (1) rapid-onset dystonia parkinsonism; (2) alternating hemiplegia of childhood; and, (3) cerebellar ataxia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome). Since their original description, an expanding number of cases presenting with atypical and overlapping features have been reported. Because of this, ATP1A3-disorders are now beginning to be viewed as a phenotypic continuum representing discrete expressions along a broadly heterogeneous clinical spectrum.

Atypical presentation of rapid-onset dystonia–parkinsonism in a toddler with a novel mutation in the ATP1A3 gene

2021 ◽  
Vol 14 (8) ◽  
pp. e244152
Author(s):  
Aishwarya Ganesh ◽  
Samyuktha Sivakumar ◽  
RanjithKumar Manokaran ◽  
Udayakumar Narasimhan
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Paediatric Population ◽  
Rapid Onset ◽  
Lower Limbs ◽  
Muscle Rigidity ◽  
Atypical Presentation ◽  
Genetic Sequencing ◽  
Atypical Presentations ◽  
Atp1a3 Gene

ATP1A3 gene mutations can result in a spectrum of diseases with diverse neurological manifestations. One such disorder linked to this mutation is rapid-onset dystonia–parkinsonism (RDP), which manifests as dystonia with features of parkinsonism, such as tremors, rigidity, muscle spasms, and bulbar symptoms. Affected patients are typically adolescents or young adults, with symptoms occurring in a rostrocaudal pattern. We report a unique case of a 2-year-old child with an early onset, atypical presentation of RDP. In addition to motor developmental delay, he presented with muscle rigidity and mild asymmetric dystonia of the limbs, with the lower limbs being more affected than the upper limbs. Genetic sequencing of the child revealed a novel heterozygous autosomal dominant mutation of ATP1A3 gene c.173A>G (p. Tyr58Cys). This report highlights that RDP can present with atypical presentations in the paediatric population and adds to existing medical literature on the clinical spectrum of ATP1A3 genetic channelopathy.

scholarly journals Alternating Hemiplegia of Childhood: A Series of Genetically Confirmed Four Cases from Southern India with Review of Published Literature

2020 ◽  
Author(s):  
Naveen Kumar Bhardwaj ◽  
Vykuntaraju K. Gowda ◽  
Ashwin Vivek Sardesai
Keyword(s):  
Neurodevelopmental Disorder ◽  
Response To Treatment ◽  
Brain Response ◽  
Significant Development ◽  
Delay In Diagnosis ◽  
Alternating Hemiplegia Of Childhood ◽  
Development Delay ◽  
The Brain ◽  
Atp1a3 Gene

AbstractAlternating hemiplegia of childhood (AHC) is a rare autosomal dominant neurodevelopmental disorder with mutation on ATP1A3 gene. Delay in diagnosis and inappropriate diagnosis are common. We describe four genetically confirmed AHC patients to provide an improved understanding of the disorder. First symptom in two patients was seizures and in other two patients was abnormal eye deviation. All had onset of plegic attacks within the first 18 months of their life. Tone abnormalities and movement disorders were present in all patients. Electroencephalogram was abnormal in two patients and all had normal magnetic resonance imaging of the brain. Response to treatment of plegic attacks was poor and also epilepsy was drug resistant. All cases had significant development delay and disability as of last follow-up. Although there is no effective treatment so far, early diagnosis is required to avoid unnecessary treatment.

scholarly journals Cardiac phenotype in ATP1A3-related syndromes

Neurology ◽  
2020 ◽  
Vol 95 (21) ◽  
pp. e2866-e2879
Author(s):  
Simona Balestrini ◽  
Mohamad A. Mikati ◽  
Reyes Álvarez-García-Rovés ◽  
Michael Carboni ◽  
Arsen S. Hunanyan ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Rapid Onset ◽  
Conduction Delay ◽  
Conduction Abnormality ◽  
Alternating Hemiplegia Of Childhood ◽  
Cardiac Phenotype ◽  
Sequence Of Events ◽  
Cardiac Assessment ◽  
Life Threatening

ObjectiveTo define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes.MethodsPatients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/−) to determine the sequence of events in seizure-related cardiac death.ResultsNinety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death.ConclusionsWe found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.

scholarly journals Expanding Phenotype of ATP1A3 - Related Disorders: A Case Series

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110480
Author(s):  
Jelena De Vrieze ◽  
Ingrid M.B.H. van de Laar ◽  
Johanneke F. de Rijk-van Andel ◽  
Erik-Jan Kamsteeg ◽  
Irene A.W. Kotsopoulos ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Cerebellar Ataxia ◽  
De Novo ◽  
Early Stage ◽  
Case Series ◽  
Rapid Onset ◽  
Sudden Onset ◽  
Intermediate Phenotype ◽  
Alternating Hemiplegia Of Childhood ◽  
Neurologic Disorders

Neurologic disorders caused by mutations in the ATP1A3 gene were originally reported as three distinct rare clinical syndromes: Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and Cerebellar ataxia, Areflexia, Pes cavus, Opticus atrophy and Sensorineural hearing loss (CAPOS). In this case series, we describe 3 patients. A mother and her daughter showed an intermediate phenotype different from each other with the same heterozygous missense mutation (p.[R756C]), recently described in literature as Relapsing Encephalopathy With Cerebellar Ataxia (RECA). In addition, a third patient showed an intermediate AHC-RDP phenotype and had a likely pathogenic novel de novo missense mutation (p.[L100 V]). These patients support the growing evidence that AHC, RDP and RECA are part of a continuous ATP1A3 mutation spectrum that is still expanding. Three common features were a sudden onset, asymmetrical neurological symptoms, as well as the presence of triggering factors. When present, the authors argue to perform exome sequencing in an early stage.

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