Startle disease: hunting down elusive genes

Babies with a rare illness called startle disease react in an exaggerated way when startled – by a loud noise, for example. They become rigid and unable to move, and sometimes stop breathing, which can prove fatal. Professor Robert Harvey of the UCL School of Pharmacy, London, and Professor Mark Rees and Dr Rhys Thomas at the Institute for Life Science, Swansea, are looking for more of the genes that cause startle disease*, in the hope of giving more babies access to a full diagnosis. This could help ensure babies get the most appropriate care. 

What is the problem and who does it affect?

We can all get startled, it is a natural response to potential danger, but for some babies this natural response is problematic. “Babies with a rare illness called startle disease react in an excessive way when startled,” explains Professor Harvey. “Their bodies become stiff and they are unable to move for a brief period. This can be as brief as a few seconds or for many minutes. Sometimes they stop breathing, which is obviously terrifying for their parents, and the disease has been linked to sudden infant death.”

Things that prompt the startle reaction include sudden, unexpected noises, movements and touches, and unexpected sight of people or objects. If diagnosed correctly, babies can be treated with drugs that help reduce this unwanted startle and can also reduce muscle stiffness. Symptoms often fade by the time babies reach their first birthday, but they can continue throughout childhood and into adulthood.

“Genetic changes in at least three genes have been linked to startle disease. Diagnosis often involves genetic testing for changes in only one of those genes (GLRA1) which is thought to be the most common cause of the disease,” says Professor Harvey. “However, many babies with startle disease do not carry any of the known genetic changes – in fact, around three fifths of cases remain unexplained, which suggests there are some genes for startle disease that we have not discovered yet.^1,2”

“This problem is heartbreaking for parents,” adds Dr Thomas. “The natural reaction of a parent is to cuddle their child close when they have a startle attack, which just exacerbates the startle by stimulating the child more. Bonding moments like feeding and dressing become a trial – as parents do their best not to startle their baby.”

* Other names for startle disease include hyperekplexia, hyperexplexia and stiff-baby syndrome.

What is the project trying to achieve?

The team is searching for more of the genetic changes that cause startle disease, using DNA samples donated by around 40 people – sufferers of the disease, and their parents and siblings. “Identifying genetic causes of startle disease that have so far eluded discovery should lead to new genetic tests for babies and children worldwide,” says Professor Rees.

Understanding the genetic causes is vital to ensure that babies get the correct treatment, as Dr Thomas explains: “Certain genetic changes, for example, cause severe breathing problems during early infancy. Training these babies’ parents in resuscitation techniques and offering monitoring of heart rate and breathing could prove to be life-saving.”

“Children with startle disease sometimes have other problems too, such as learning difficulties. Knowing the genetic causes of each child’s illness enables us to predict more accurately what sort of educational needs they are likely to have in the future, which will help parents gain access to appropriate support services.”

What are the researchers’ credentials?

This study is a joint effort between Professor Robert Harvey of the UCL School of Pharmacy, London and Professor Mark Rees and Dr Rhys Thomas at the Institute for Life Science, Swansea. These researchers have had a productive working relationship over the past ten years and have identified genetic causes of several childhood disorders, including startle disease.

References

1. Harvey RJ, Topf M, Harvey K, Rees MI (2008) The genetics of hyperekplexia: more than startle! Trends in Genetics 24: 439-447.
2. Thomas RH, Stephenson JBP, Harvey RJ, Rees MI (2010) Hyperekplexia: Stiffness, startle and syncope. Journal of Pediatric Neurology 8: 11-14.