Monogenic dystonia refers to forms of dystonia caused by a single gene mutation. These disorders often have distinct clinical features and inheritance patterns (autosomal dominant, autosomal recessive, or X-linked).
Dystonia characterized by involuntary muscle contractions, resulting in twisting, repetitive movements or abnormal postures, directly attributable to mutations in one specific gene.
Autosomal dominant (e.g., DYT1 dystonia due to mutations in TOR1A gene).
Autosomal recessive (e.g., dystonia associated with mutations in TH or GCH1 genes).
X-linked (rare, associated with mutations in the TAF1 gene, causing X-linked dystonia-parkinsonism or Lubag).
| Dystonia Type | Gene | Inheritance | Key Features | Treatment |
|---|---|---|---|---|
| DYT1 | TOR1A | Autosomal dominant | Early-onset, limb onset, generalizes, Ashkenazi Jewish | DBS (GPi), anticholinergics, botulinum toxin |
| DYT5 (A/B) | GCH1 / TH | AD / AR | Childhood onset, diurnal fluctuation, excellent levodopa response | Levodopa (dramatic response) |
| DYT6 | THAP1 | Autosomal dominant | Variable onset, cranial/cervical involvement, speech affected | DBS, pharmacologic (limited effect) |
| DYT11 | SGCE | AD with maternal imprinting | Myoclonus + dystonia, alcohol-responsive | Clonazepam, DBS, alcohol (transient relief) |
| DYT16 | PRKRA | Autosomal recessive | Early-onset generalized dystonia, rapidly progressive | Limited response to meds; DBS considered |
| DYT3 (Lubag) | TAF1 | X-linked recessive | Filipino males, adult-onset dystonia-parkinsonism | Limited; anticholinergics, levodopa |
| DYT-TUBB4A | TUBB4A | Autosomal dominant | Whispering dysphonia (laryngeal), adult onset | Botulinum toxin, DBS in select cases |
| Gene / Syndrome | Clinical Features | Treatment |
|---|---|---|
| DYT1 (TOR1A) | Childhood or adolescent-onset generalized dystonia, usually starting in limbs, no other neurological signs | GPi-DBS (highly effective)Anticholinergics, benzodiazepines, baclofen (variable effect) |
| DYT6 (THAP1) | Similar to DYT1 but more frequent cranio-cervical involvement; later onset possible | GPi-DBS (less predictable response than DYT1)Symptomatic treatment |
| DYT11 (SGCE) (Myoclonus-dystonia) | Myoclonus and dystonia, improves with alcohol, autosomal dominant with maternal imprinting | Clonazepam, levetiracetam, other GABAergic drugsGPi-DBS in severe cases |
| DYT5a (GCH1) (Dopa-responsive dystonia) | Childhood-onset, fluctuating dystonia, diurnal variation, excellent response to levodopa | Low-dose levodopa (dramatic and sustained improvement) |
| DYT12 (ATP1A3) (Rapid-onset dystonia-parkinsonism) | Sudden onset, fixed dystonia, ataxia, parkinsonian features | Poor response to medicationsDBS (variable benefit) |
| DYT-TUBB4A (H-ABC syndrome) | Dysarthria, dystonia, cerebellar atrophy, mixed symptoms | Symptomatic treatment, physiotherapyDBS with experimental results |
| DYT-PARK (PRKRA) | Dystonia-parkinsonism, often juvenile onset | Levodopa (helpful in some cases)GPi-DBS (variable outcomes) |
A systematic review protocol, designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to evaluate the efficacy and safety of Deep Brain Stimulation in patients with monogenic dystonia — a subset of rare, genetically defined dystonias caused by mutations in single genes 1).
This protocol is highly relevant for neurosurgeons involved in functional neurosurgery, especially those performing Deep brain stimulation for movement disorders. By focusing on genetic subtypes of dystonia, it may inform future patient selection, target choice, and timing of intervention.