A 6-year-old girl is one of more than 80 people worldwide who has finally received a diagnosis of a new condition following a landmark breakthrough by scientists and doctors in Manchester.
Ava Begley’s parents say they feel “deeply grateful” that the researchers, from Manchester University NHS Foundation Trust (MFT) and The University of Manchester (UoM), have made this discovery, which is one of the most common genetic causes of severe epilepsy.
Delivered through the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC), this groundbreaking work is already transforming the lives for many children and young people around the world, providing long-awaited answers and hope for the future.
Ava’s parents, Daniel Begley and Elizabeth Dowd, from Sydney, Australia, said: “Our first reaction was a mixture of emotion – relief at finally having a diagnosis, but also sadness in understanding the seriousness of the condition and how rare it is. Above all, we felt grateful that Ava’s experience may contribute to greater knowledge and future progress and treatment.”
This new condition, which the researchers have named as “Recessive RNU2-2-related neurodevelopmental disorder”, results in difficult-to-control seizures and severe developmental delays in children, often appearing within their first year of life.
Published in the journal Nature Genetics, the research has so far identified 84 individuals living with the new condition, while experts estimate that thousands more remain undiagnosed across the world.
The team estimates that millions of people globally could be ‘carriers’ of the faulty gene behind this disorder.
Study lead and first author of the paper Dr Adam Jackson, Academic Clinical Fellow at the Manchester Centre for Genomic Medicine, part of MFT, and The University of Manchester, explained: “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.”
This major advance builds on another recent discovery made last year by the Manchester team in which they showed the importance of the RNU genes in brain development and function.
The research team made the new discovery by analysing changes in several hundred RNU genes in data of individuals who took part in the 100,000 Genomes Project, a Genomics England initiative to sequence and study the role genes play in health and disease.
Dr Jackson, who is also an early career researcher in the NIHR Manchester BRC’s Rare Conditions Theme, explained: “What makes this discovery even more remarkable is that RNU2-2 is extremely small in comparison to other genes. Unlike most other genes, RNU2-2 does not even make a protein. We were astonished to discover how changes in this tiny gene can have such profound effects in so many individuals.”
Children with the condition experience severe epilepsy early on in life, often in their first year. This means they have seizures – sudden surges of electrical activity in the brain which can cause the body to stiffen, jerk, shake and lose consciousness. These seizures can be difficult to fully control with medication, highlighting the urgent need for improved therapies.
The condition also has a profound impact on brain development, causing delays or inability to achieve key milestones such as walking or talking. Almost all affected individuals have significant learning problems.
Ava’s story
6-year-old Ava has lived with complex neurological symptoms from early childhood and requires full-time care and ongoing medical support.
Ava’s condition includes developmental delay, profound intellectual disability and severe epilepsy with frequent seizures. She would often experience 100 to 200 seizures per day, but these are now more controlled with medication.
Ava is non-verbal and cannot communicate through speech or gestures. She requires full-time support with daily life, including bathing, toileting and feeding. She also experiences major motor and balance difficulties, can only walk short distances and falls frequently. Ava often bites and pulls hair out and screams in frustration.
Collaborating with Manchester researchers, the Sydney Children’s Hospital Clinical Genetics Team who support Ava and her family, were able to link Ava’s condition to the newly identified recessive RNU2-2-related disorder.
“The University of Manchester is a public research university in Manchester, England. The main campus is south of Manchester City Centre on Oxford Road.”
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