[MIM 128 235]

(Dystonia-Parkinsonism with early onset)

Rare: < 1/106. De novo mutation or autosomal dominant transmission of a mutation of the ATP1A3 gene (19q12-q13.2) coding for the subunit alpha 3 of the Na-K-ATPase protein. Other mutations of the same gene produce hemiplegia alternans of infancy or the CAPOS syndrome.

Clinical presentation:

• usually onset in childhood or early adulthood
• acute orofacial dystonia, often triggered by stress factors (physical exhaustion, fever, extreme heat, childbirth, excessive alcohol consumption or emotional stress) and with a rostro-caudal onset progression
• bradykinesia and postural instability, with bulbar symptomatology (dysarthria, dysphagia)
• dystonic spasms, especially in the upper limbs, without tremor or dyskinesia
• and signs and symptoms stabilize within one month of their onset

In rare cases, convulsions, anxiety and depression have been observed. A variant has recently been reported in young children (4 years of age) with initial episodic hypotonia, locomotor ataxia, motor retardation, and speech and swallowing disorders.

Diagnosis: based on the sudden onset of clinical manifestations (Parkinson's syndrome and dystonia), low levels of homovanillic acid in CSF, normal brain imaging and a lack of response to levodopa (L-dopa) treatment.

Treatment: no effective treatment at this time. L-dopa has no effect. Deep brain stimulation has shown limited or non-existent therapeutic effects. In case of seizures, anxiety or depression, the usual treatments may be prescribed. High-dose benzodiazepines and other muscle relaxants can relieve symptoms. Symptomatic treatment with baclofen or botulinum toxin injections. Physical therapy is recommended.

Anesthetic implications: 

preoperative anxiolysis. Dysphagia: risk of aspiration; drug interactions with baclofen.  Avoid dopaminergic drugs: haloperidol, dehydrobenzperidol, metoclopramide.

References : 

• Leroy P, Meyer F, Vaessen S, Doummar D, Misson J-P.
  Dystonie de type 12 : un diagnostic rare et difficile.
  Arch Pédiatr 2017; 24 : 637-9.
• Sampson JB, Michaeli TH, Wright BA, Goldman JE, Vonsatte J-P, Stanley Fahn S.
  Basal Ganglia Gliosis in a Case of Rapid-Onset Dystonia-Parkinsonism (DYT12) with a Novel Mutation in ATPase 1A3 (ATP1A3).
  Movement Disorders 2016 ; doi:10.1002/mdc3.12354
• Hardy P-Y, Hallet C, Kirsch M,  Samalea Suarez N, Hic G, Petry J,  Lois F,  Jastrowicz, J, Depierreux F.
  Anesthetic management of a child with Rapid-Onset Dystonia-Parkinsonism (DYT12-ATP1A3): a case report.
  A & A Practice ; 2021 15:e01440.

Updated: April 2021