Remarkable recovery in patients diagnosed with newly defined movement disorder

Researchers from the UCL Great Ormond Street Institute of Child Health have discovered a new gene change that identifies a type of the movement disorder, muscle dystonia. This new discovery will allow doctors to more easily identify patients who can benefit from treatment so effective that it can restore the ability to walk.

The team from UCL Great Ormond Street Institute of Child Health, along with colleagues at the University of Cambridge and the NIHR Rare Disease Bioresource, identified a change in a gene, called KMT2B, in 28 patients who had dystonia.

Dystonia is one of the most common movement disorders and is thought to affect 70,000 people in the UK. It can cause a wide range of disabling symptoms, including painful muscle spasms and abnormal postures, and can affect walking and speech. In most of the 28 cases, the patients — many of whom were young children who were thought to have a diagnosis of cerebral palsy — were unable to walk.

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

Given the findings, the team now suggest that testing for these changes in the gene should form part of standard testing for patients with dystonia. This will allow the most effective treatment to be offered to patients early on.

Dr Manju Kurian, paediatric neurologist at Great Ormond Street Hospital and lead researcher on the paper, says “Through DNA sequencing, we have identified a new genetic movement disorder that can be treated with Deep Brain Stimulation. This can dramatically improve the lives of children with the condition and enable them to have a wider range of movement with long-lasting effects,”

“Remarkably nearly all patients who had Deep Brain Stimulation showed considerable improvements. One patient was able to walk independently within two weeks; in five patients, the improvement has lasted for more than three years. It is an astounding result.”

The research was published in Nature Genetics on Monday 19 December 2016.

Sarah's daughter, Katie,12, was diagnosed with dystonia at GOSH will soon be undergoing deep brain stimulation treatment:

“When Katie was little, she would often fall over and lose her balance, but I put it down to clumsiness. By the age of almost five, we noticed that Katie would fall back as she stood and activities such as riding a bike took a lot of effort and concentration. We went to the doctors and were told she had global developmental delay, but that her motor skills would improve over time.

“Katie’s problems persisted and we were referred to a neurologist for tests. Eventually doctors told us that they thought Katie had dystonia. It was the first time we’d heard of this condition. Although all the signs pointed to this diagnosis, doctors still couldn’t confirm this – she could have also had dyspraxia, cerebral palsy or Huntingdon’s disease.

Coming to GOSH

“When Katie was eight, she was referred to Dr Kurian at GOSH. By then Katie could only walk for short distances and had a wheelchair.  It was wonderful to be transferred with the hope that someone would be able to help us. Dr Kurian was so welcoming and warm. She put us at ease straight away and suggested many ideas to help diagnose exactly what Katie had. She was determined to continue until we had answers. Eventually Dr Kurian had a breakthrough and discovered a brand new gene that could prove that Katie had a specific type of dystonia.

“While Dr Kurian was searching for this gene, we were also referred for Deep Brain Stimulation surgery.

“The discovery of the gene that was causing Katie’s dystonia meant that we could compare Katie’s case with others who also had this gene to see how successful their surgery had been. This was reassuring but the decision for Katie to have the surgery was still incredibly difficult for myself and my husband. We both felt differently about it. My husband recognised that the surgery was the only thing they could do, and we would have to take that chance to give Katie the best quality of life. But I did not want to put her through any pain. We were opposite in our views until we met with the surgical team where we told the details of the operation. They were all so happy and positive, I came away from the meeting knowing that this was the right thing for Katie.

Preparing for future surgery

“As a mother having to sign permission for them to operate on my daughter is the worst thing ever, but I know it is the best chance she is going to get. Meeting the surgeon face to face really helps and allows you to develop a personal connection, it alleviates all of your worries.

“Katie’s six to eight hour operation will be taking place next month. While we want to stay grounded, seeing success stories fills us with hope. In some cases, there have been drastic changes to children after the operation and they have started to walk again. Our main hope is that Katie will get some of her independence and mobility back, and is able to feel more included in life rather than sitting on the side-lines watching everybody else.

“Despite everything, Katie is an extremely happy child with a positive outlook on life.  She adores television and takes sole ownership of the remote control at home. She also beats the rest of the family at bowling by a mile! Every movement at the moment is tiring for her though, so we’re hoping that the surgery is the beginning of an exciting new chapter for her.

“I’m over the moon we were transferred to GOSH. You wouldn’t want to be anywhere else. You can’t help but feel special as you know that’s where the best people in their field will be.”

Former GOSH patient, Dominika, aged 21, was diagnosed with dystonia when she was 13 and had deep brain stimulation treatment two years ago:

When I was young I was able to speak and write normally but I started to have problems with walking when I was about 10. By the time I was 11 or 12, my walking had got worse and

I started to notice my writing and speech was deteriorating.

Throughout high school, I had lots of different tests to try and find out what was wrong with me and I first came to GOSH just after my 13th birthday. They gave me lots more tests and told me that I had a type of dystonia which means my muscles aren’t working properly and I can’t move my body as well as I should.

By the time I got to the last year in high school, I was finding walking very difficult and so I started using a wheelchair because it was easier and less painful.

I was given a drug treatment for my dystonia but it didn’t seem to be making things much better so when I was 19, I was offered deep brain stimulation surgery.

Since the operation, life has been good and the surgery has really changed things for me. It has allowed me to walk around mostly unaided. I have seen a big difference with my hands - I can now write and draw, something I wasn’t able to do before. Now, I just do physiotherapy exercises at home to keep my movement as strong as possible. This has meant that I have been able to go to university and I am currently in my final year studying Computer Game Art. I get to practise my drawing using traditional and digital media, and hopefully one day I can get a job doing the two things I love best, drawing and playing video games.