Pediatric Movement Disorders - Dystonia: Etiology

Pediatric Movement Disorders - Dystonia

Etiology

Primary:
Multiple genes for dystonia have been found, causing autosomal dominant inheritance. These include...

DYT1 (9q34, encodes torsinA)
DYT4
DYT5 (14q22.1-2, encodes GTP cyclohydrolase I, leading to Dopa-responsive dystonia or Segawa's disease)
DYT6 (8p21-q22)
DYT7 (18p)
DYT8 (2q33-q35, causing paroxysmal non-kinesogenic choreoathetosis PNKC)
DYT9 (1p, causing PNKC and spasticity)
DYT10 (16p11.2-q12.1, causing paroxysmal kinesogenic choreoathetosis, PKC)
DYT11 (heterogeneous, causing familial myoclonus-dystonia)
...and there are more genes discovered every year

Other genes for dystonia include...

DYT2 (an autosomal recessive trait)
DYT3 (an X-linked dystonia-parkinsonism syndrome of Lubag (Xq13)
There is also a familial rapid-onset dystonia-parkinsonism (linked to chromosome 19)

Fixed Injury/Structural:
Cerebral palsy (often with delayed onset); kernicterus (in severe jaundice due to high bilirubin levels); hypoxic injury; head trauma; encephalitis; tumors; stroke in the basal ganglia (a rare result of varicella (chicken pox) or vascular abnormalities including Moya-Moya disease); congenital malformations

Degenerative:
Fahr's disease (or basal ganglia calcification); pantothenate-kinase associate neurodegenerative disease (PKAN, formerly neurodegeneration with brain iron accumulation type I, formerly Hallervorden-Spatz disease, PANK2 gene at 20p12.3-p13); Huntington's disease (Westphal variant, IT15-4p16.3); spinocerebellar ataxias (SCAs); neuronal ceroid lipofuscinosis; Rett syndrome; Tay-Sachs disease; Sandhoff's disease; Niemann-Pick type C; metachromatic leukodystrophy; striatal necrosis; Leigh's disease; neuroacanthocytosis; vitamin E deficiency; HARP syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration); Pelizaeus-Merzbacher disease; ataxia-telangiectasia (AT)

Chemical/Metabolic:
Glutaric aciduria; acyl-CoA dehydrogenase deficiency dopa-responsive dystonia or DRD (biopterin metabolic defect DYT5 or tyrosine hydroxylase deficiency); dopamine agonist-responsive dystonia (or ALAD: aromatic L-amino acid decarboxylase deficiency); mitochondrial disorders; Wilson's disease; homocystinuria; GM1 gangliosidosis; metachromatic leukodystrophy; Lesch-Nyhan disease; methylmalonic aciduria; tyrosinemia

Drug- or Toxin-induced:
(Drug- or toxin-induced dystonia may occur while taking the drug or months after stopping the drug.) Neuroleptic and anti-emetic medications (e.g., haloperidol, thorazine, olanzapine, risperidone, quetiapine, promethazine, prochlorperazine, etc.); calcium channel blockers; stimulants (e.g., amphetamine, cocaine, ergot alkaloids, etc.); anticonvulsants (e.g., carbamazepine, phenytoin, etc.); thallium; manganese; carbon monoxide; ethylene glycol; cyanide; methanol; wasp sting

Paroxysmal:
Paroxysmal kinesogenic choreoathetosis (PKC); paroxysmal non-kinesogenic choreoathetosis (PNKC); familial periodic paralysis; exercise-induced dystonia; complex migraine; alternating hemiplegia; paroxysmal torticollis of infancy

Disorders That Mimic Dystonia:
Tonic seizures (including paroxysmal nocturnal dystonia caused by nocturnal frontal lobe seizures); syringomyelia; Arnold-Chiari malformation type II; atlanto-axial subluxation; posterior fossa mass; cervical spine malformation (including Klippel-Feil anomaly); ocular skew deviation with vertical double vision causing neck twisting, juvenile rheumatoid arthritis; Sandifer's syndrome (gastrointestinal disorder associated with hiatus hernia in infants); spasmus nutans; tics; self-stimulation; spasticity; myotonia; rigidity; stiff-person syndrome; Isaac's syndrome; startle disease (hyperexplexia); neuroleptic malignant syndrome; psychogenic disorders