New Genetic Cause Discovered for Dystonia

Dystonia is one of the commonest movement disorders and is thought to affect 70,000 people in the UK alone. It can cause a wide range of disabling symptoms, including painful muscle spasms and abnormal postures, and can affect walking and speech.

For some patients, treatment with Deep Brain Stimulation, in which electrical impulses are delivered to a specific brain region involved in movement, either restored or significantly improved independent walking and improved hand and arm movement. In one patient, improvements have been sustained over six years.


A large team of scientists working under the auspices of the University College London (UK) and Great Ormond Street Hospital (London, UK) tested 27 unrelated individuals and discovered a region of chromosome 19 that was deleted from the genome of some patients with childhood-onset dystonia. Together with the NIHR Rare Disease Bioresource and international collaborators, the team then identified abnormal genetic changes in genomes from a further 18 patients in one gene, called Lysine Methyltransferase 2B (KMT2B), where affected patients carried a mutatation in their DNA.

The 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. The team believes that the mutations impair the ability of the KMT2B protein to carry out its normal, crucial role in controlling the expression of genes involved in voluntary movement. The team believes that the mutations impair the ability of the KMT2B protein to carry out its normal, crucial role in controlling the expression of genes involved in voluntary movement.

Manju Kurian, MBBCh, PhD, an academic pediatric neurologist and senior author of the study, said, “Most patients show a progressive disease course with worsening dystonia over time. Many patients did not show any response to the usual medications that we use for dystonia so we knew we would have to consider other strategies. We know, from our experience with other patients with dystonia, that Deep Brain Stimulation might improve our patient’s symptoms, so were keen to see what response patients would have to this type of treatment.” The study was published on December 19, 2016, in the journal Nature Genetics.

Related Links:
University College London
Great Ormond Street Hospital