Objective: Functional neurologic disorder (FND) diagnostic criteria continues to evolve, with current emphasis on positive neurologic signs, including sudden onset, inconsistency or incongruence, without reliance on presence or exclusion of other disorders, such as psychological or historical stressors. We present two cases of genetically confirmed ATP1A3 mutations and clinical features of rapid-onset dystonia parkinsonism (RDP) with functional neurologic disorder (FND) phenotypes.

Background: Case 1(C1): 16y/o F with history of anxiety, abuse, and OCD presented with one year of sub-acute generalized appendicular dystonia without axial involvement.Three years from initial onset, patient had a psychologically traumatic event. She had acute, severe, sustained anarthria and jaw opening dystonia. Prior hand/leg dystonia transiently improved, despite stark progression of bulbar symptoms.  Case 2(C2): 18y/o F with history of anxiety and childhood trauma presented with acute symptoms of fixed distal dystonia following a triggering event. A variety of abnormal movements followed, some rapidly progressed, others were intermittent.  She had a period of relative remission a month later. Both saw multiple movement disorder specialists and were initially diagnosed with FND.

Method: MRI brain and thorough laboratory workup for both patients was unremarkable, including paraneoplastic panel and Wilson’s disease testing. Both patients failed trials of carbidopa-levodopa, and were unable to tolerate baclofen, but receive botulinum toxin injections for dystonia with some efficacy. Trihexyphenidyl was moderately beneficial. Both received counseling for childhood traumas, including stressors linked to initial dystonic events.

Results: C1: heterozygous ATP1A3 gene variant c.2417T>G(p.Met806Arg). This possible pathogenic mutation was described in a patient with the AHC phenotype.  C2: heterozygous ATP1A3 gene variant c.2767G>A(p.Asp923Asn).This is a known pathogenic mutation previously reported in patients with RDP.

Conclusion: Greater availability of genetic testing and improved understanding of ATP1A3 mutations and phenotypes can accelerate accurate diagnosis and treatment. The phenotypic spectrum of genetic dystonias continues to expand, and multiple variants feature overlapping clinical features. Providers should be aware that a positive FND diagnosis does not exclude organic disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/atp1a3-gene-mutations-associated-with-rapid-onset-dystonia-parkinsonism-rdp-presenting-as-functional-neurologic-disorder-a-report-of-two-cases/