Revising rapid-onset dystonia-parkinsonism: Broadening indications for ATP1A3 testing.

Autor: Haq IU; Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Snively BM; Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Sweadner KJ; Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA., Suerken CK; Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Cook JF; Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Ozelius LJ; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA., Miller C; Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., McCall WV; Department of Psychiatry and Health Behavior, Medical College of Georgia August University, Augusta, Georgia, USA., Whitlow CT; Department of Radiology, Section of Neuroradiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Brashear A; Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2019 Oct; Vol. 34 (10), pp. 1528-1536. Date of Electronic Publication: 2019 Jul 30.
DOI: 10.1002/mds.27801
Abstrakt: Background and Objectives: Rapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene, which codes for the α-3 subunit of the Na + /K + ATPase. It has been characterized by rapid-onset bulbar dysfunction, limb dystonia, bradykinesia, and a rostrocaudal spatial gradient of expression, usually after a physiologic trigger. We reexamined whether these features were in fact characteristic.
Methods: We characterized phenotypic variation within a cohort of 50 ATP1A3 mutation-positive individuals (carriers) and 44 mutation-negative family members (noncarriers). Potential participants were gathered through referral for clinical suspicion of RDP or alternating hemiplegia of childhood. Inclusion criteria were having a ATP1A3 mutation or being a family member of such an individual.
Results: We found RDP is underdiagnosed if only "characteristic" patients are tested. Rapid onset and bulbar predominance were not universally present in carriers. Among those with at least mild symptoms of dystonia, rostrocaudal severity gradient was rare (7%). Symptoms began focally but progressed to be generalized (51%) or multifocal (49%). Arm (41%) onset was most common. Arms and voice were typically most severely affected (48% and 44%, respectively). Triggers preceded onset in 77% of the participants. Rapid onset, dystonia, parkinsonism, bulbar symptoms, headaches, seizures, frontal impairment, and a history of mood disorder and a history of psychosis were more common in carriers. Approximately half of the proband mutations occurred de novo (56%).
Conclusions: Our findings suggest that patients should not be excluded from ATP1A3 testing because of slow onset, limb onset, absent family history, or onset in middle adulthood. RDP should be strongly considered in the differential for any bulbar dystonia. © 2019 International Parkinson and Movement Disorder Society.
(© 2019 International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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