We present two cases of genetically confirmed ATP1A3 mutations with clinical features of rapid-onset dystonia-parkinsonism (RDP) and overlapping functional neurologic disorder (FND) phenotypes.

(see videos)

Case 1 (C1): 16y/o F with history of anxiety, abuse, and OCD presented with one year of sub-acute distal >proximal appendicular dystonia, R>L side, without axial involvement. R hand dystonia worsened with stress.

Following a traumatic event three years from onset, patient had acute, severe, sustained anarthria and jaw opening dystonia. Interestingly, she had improvement in hand and leg dystonia, 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.

MRI brain and thorough laboratory workup for both patients was unremarkable, including paraneoplastic panel and Wilson’s disease testing.

Genetic Testing

C1: Invitae Dystonia Comprehensive Panel (18 genes analyzed)

C2: Massachusetts General Neurogenetics test for RDP, ATP1A3 mutation analysis

Both patients failed trials of carbidopa-levodopa, and were unable to tolerate baclofen, but receive botulinum toxin injections for dystonia. Trihexyphenidyl was moderately beneficial.

C1: heterozygous ATP1A3 gene variant c.2417T>G (p.Met806Arg).

This possible pathogenic mutation is described in a patient with alternating hemiplegia of childhood

C2: heterozygous ATP1A3 gene variant c.2767G>A(p.Asp923Asn).

This pathogenic mutation is described in patients with RDP

Greater availability of genetic testing and improved understanding of ATP1A3 mutations and phenotypes may be useful for diagnosis, but do not rule out FND overlay.