Dystonia
Neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.
The movements may resemble a tremor.
Classification
Etiology
The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to pharmaceutical drugs, particularly neuroleptics.
Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases.
Meyer et al., we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement 1).
Children with cerebral palsy (CP) can present with severe secondary dystonia with or without associated spasticity of their extremities.
Pathophysiology
Clinical features
Dystonia is often initiated or worsened by voluntary movements, and symptoms may “overflow” into adjacent muscles.
Treatment
see Dystonia treatment.
Outcome
Response is better for primary dystonias than for secondary dystonias. 2).
Good responses have also been reportes with subthalamic nucleus deep brain stimulation.
DBS as treatment for medication-refractory dystonia, on the other hand, may increase the risk of suicide in patients. However, reference data of patients without DBS therapy are lacking.