Browsing by Author "Padiath, Quasar S. (6507370990)"

Objective Identification and characterization of a novel pedigree with ATP1A3 mutations presenting with CAPOS syndrome and hemiplegic migraine. Methods We have carried out clinical examinations of a three-generation pedigree with CAPOS syndrome and analyzed the ATP1A3 gene to identify causative mutations. The pedigree is of Slavic origin from Southeastern Europe. Results The clinical phenotype comprised cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing loss. Pes cavus was present in two of the four patients studied. The symptoms were triggered by fever and varied in severity in family members, exhibiting a chronic progressive course with or without relapses/remissions. The ATP1A3 c.2452G > A mutation was identified in the affected members of the family, while one of the mutation carriers exhibited both CAPOS and hemiplegic migraine. Conclusions This study confirms that the specific c.2452G > A mutation in the ATP1A3 gene is associated with the CAPOS syndrome in pedigrees of different ethnic backgrounds. In patients with febrile episodes of ataxic encephalopathy or weakness, or both, genetic analysis of the ATP1A3 gene should be warranted. This is also the first report showing the co-occurrence of hemiplegic migraine and CAPOS syndrome in a patient with ATP1A3 mutations. Migraine has not been previously documented in ATP1A3 mutation carriers. © 2015 Elsevier B.V.

Objective Identification and characterization of a novel pedigree with ATP1A3 mutations presenting with CAPOS syndrome and hemiplegic migraine. Methods We have carried out clinical examinations of a three-generation pedigree with CAPOS syndrome and analyzed the ATP1A3 gene to identify causative mutations. The pedigree is of Slavic origin from Southeastern Europe. Results The clinical phenotype comprised cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing loss. Pes cavus was present in two of the four patients studied. The symptoms were triggered by fever and varied in severity in family members, exhibiting a chronic progressive course with or without relapses/remissions. The ATP1A3 c.2452G > A mutation was identified in the affected members of the family, while one of the mutation carriers exhibited both CAPOS and hemiplegic migraine. Conclusions This study confirms that the specific c.2452G > A mutation in the ATP1A3 gene is associated with the CAPOS syndrome in pedigrees of different ethnic backgrounds. In patients with febrile episodes of ataxic encephalopathy or weakness, or both, genetic analysis of the ATP1A3 gene should be warranted. This is also the first report showing the co-occurrence of hemiplegic migraine and CAPOS syndrome in a patient with ATP1A3 mutations. Migraine has not been previously documented in ATP1A3 mutation carriers. © 2015 Elsevier B.V.

Objective To 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. Copyright © 2020 American Academy of Neurology.