Study reveals genetic link between childhood brain disorder and Parkinson's disease

Research lead by Evelina London clinicians and King's College London researchers into a rare neurodevelopment condition has provided important insights into a more common age-related disorder.

The new study, published in the Annals of Neurology has found that errors in a gene known to cause Vici syndrome in infants are also linked to the development of Parkinson's disease in adolescence and adulthood.

Vici syndrome is an extremely rare and severe inherited neurodevelopmental condition. Symptoms start early in life and affect multiple organs. The condition is due to errors in the gene EPG5, originally identified as the cause of Vici syndrome by the King’s College London team in 2013, with currently fewer than 10 children known to have the condition in the UK.

In the largest study of its kind to date, Professor Heinz Jungbluth, professor of paediatric neurology at King's College London and consultant paediatric neurologist at Evelina London Children's Hospital, together with the wider research team analysed clinical and genetic data from 211 individuals from across the world with rare errors in EPG5. They found that the effects of these genetic errors are broader and more variable than previously known. While some individuals had life-limiting forms of Vici syndrome identified before or shortly after birth, others showed much milder symptoms, including delay in movement, speech, and learning.

The researchers also discovered that some participants went on to develop a breakdown of nerve cells in adolescence or early adulthood that led to Parkinson's disease and dementia. Brain scans in some cases showed additional iron build-up, a feature of other, closely-linked neurodevelopmental disorders.

To explore what was causing the cell breakdown, the researchers studied samples taken from participants with Vici syndrome and organisms, including mice, fruit flies and the tiny roundworm C. elegans, that errors in EPG5 had been introduced into. Their experiments showed that genetic errors in the gene stop cells from clearing out damaged parts, leading to the build-up of proteins closely associated with Parkinson's disease.

Professor Heinz Jungbluth said: "This study could never have been possible without the support and collaboration of the Vici Syndrome Foundation and families affected by Vici syndrome and we are enormously grateful to everyone who has been involved.

"Our work shows that, whilst not often considered a priority, research into very rare conditions such as Vici syndrome may provide vital insights into much more common disorders such as Parkinson's disease and have substantial public health benefits.

"Understanding the causes of these challenging and often life-limiting diseases is essential for developing treatments and offers hope for patients and their families.

"The study provides new understanding of how damage at a cellular level can underpin a range of lifelong neurological conditions and may help pave the way for future treatments that target these shared drivers of disease."

The research team involved experts from Evelina London Children's Hospital, King's College London, University College London (UCL), the University of Cologne and the Max Planck Institute for Biology of Ageing, Cologne, Germany.