Scientists in Manchester have identified a major new genetic cause of severe epilepsy in children, in a discovery that could help provide long-awaited answers for families worldwide.
Researchers at Manchester University NHS Foundation Trust and The University of Manchester, working through the NIHR Manchester Biomedical Research Centre, have identified a newly recognised condition called recessive RNU2-2-related neurodevelopmental disorder.
The condition causes difficult-to-control seizures and profound developmental delays, usually beginning in the first year of life.
The findings have been published in Nature Genetics.
Among the first children to receive a diagnosis is six-year-old Ava Begley, whose parents said they feel “deeply grateful” for the discovery after years without answers.
Researchers have so far identified 84 children and young people worldwide with the condition.
However, experts estimate that thousands more may remain undiagnosed, while millions of people globally could be carriers of the faulty gene.
The discovery builds on the team’s earlier work showing the important role of RNU genes in brain development and function.
It marks the second major advance in this field within a year.
Scientists made the discovery by analysing changes in several hundred RNU genes using data from the 100,000 Genomes Project, a Genomics England initiative designed to improve understanding of how genetic variation influences health and disease.
The newly linked gene, RNU2-2, plays a role in how the brain processes certain proteins.
A recessive fault in the gene disrupts normal neurological development and triggers the severe symptoms seen in affected children.
Children with the disorder experience early-onset seizures, caused by sudden bursts of electrical activity in the brain.
These can lead to stiffness, jerking or shaking, loss of consciousness and frequent uncontrolled episodes.
The seizures are often resistant to medication, highlighting the need for new targeted therapies.
Dr Adam Jackson, academic clinical fellow at the Manchester Centre for Genomic Medicine, said: “We believe that as many as in 1 in 100 people could unknowingly be carriers of this condition.
“If both parents are carriers, there is a 1 in 4 chance with every pregnancy that their child could be affected.
“We estimate roughly 1 in 40,000 people may be living with this condition, making it one of the most common neurodevelopmental disorders currently known.
“Our discovery brings hope for many patients and families who have been searching for answers and is already having a positive impact around the world.”
Beyond seizures, the condition can have a profound impact on development.
Many affected children do not reach key milestones such as walking or talking, have significant or severe learning difficulties and require lifelong care and support.
For families, a diagnosis can bring clarity after years of uncertainty and help open access to more appropriate support, tailored treatment and international networks of families affected by the same rare condition.
There is currently no cure for the disorder.
However, researchers said identifying the genetic cause is an essential first step towards diagnostic tests, earlier intervention, better-targeted treatments and the future development of gene-specific therapies.
The Manchester team will now continue work to improve diagnostics, support families and clinicians, and explore new treatment pathways.