Living In the Dark: Genetics, Diagnosis and Uncertainty. By Simon Hazelwood-Smith

Progress in genetics is remarkable. We know of over 6000 mutations that cause disease, have created fully functional synthetic chromosomes and are seeing gene therapy successfully restore sight and hearing. The human genome sequence was completed in 2003, representing $3 billion of investment and 13 years of work. Whole genome sequencing now costs $1000 and takes one day.

Nevertheless there remain thousands of people affected by genetic disease; in fact 60% of us will be affected in some way in our lifetimes. At birth this number drops to around 3%, meaning that there are 13,000 children born each year with a genetic condition.

Given the unrelenting advances in our understanding of genetics, it is perhaps a surprise that, currently, around 50% of children born with a genetic condition will receive no specific diagnosis.

Children lacking a diagnosis are grouped together with the blanket term ‘Syndromes without a name’ or SWAN. A tag of SWAN on a child can signify the start of dozens of tests, hospital time, disappointment and frustration.

The impacts of this on parents are both emotionally distressing and practically challenging. A common sentiment is a strong feeling of isolation, that there is no one who truly understands what is going on, or how best to help them.

This isolation is heightened when parents come to explain their child’s difficulties to others. “There is a lack of awareness that it is even possible for disabled children to not have a diagnosis.” Says Lauren Roberts of the charity SWAN UK, which supports families of SWAN children.

“Parents will often hear comments like ‘oh well at least it’s not that serious’ or ‘maybe they will grow out of it then’ even though their child may have profound and complex needs”

When it comes to access to NHS care and support from social services, a lack of a diagnosis can become a huge stumbling block. Although needs based assessments are used in social care, these often rely on there being a known medical condition. “We still see our members being turned away because they cannot put a name to their condition” Says Nick Meade, director of policy at the Genetic Alliance.

One of the key issues of non-diagnosis is that it prevents reliable prognosis. Families do not know if a child will ever learn to talk or walk, if they will stabilise or get worse or, tragically, how long they might live. “These questions are important for planning family life. Will a parent have to give up their job? Will the family home be suitable for their child in the future?” says Mr. Meade.

Additionally, the lack of diagnosis prevents reliable family planning. In conditions with a known mutation the likely risk of reoccurrence can be calculated, this isn’t possible for SWAN children.

How is it that so many children slip through the net of diagnostics? Currently many diagnostic NHS genetics laboratories test a specific gene or set of genes for given symptoms. However, if these come back negative, there are often not facilities to cast the net wider into genes that have not previously been implicated.

However this may soon begin to change. In 2013 an NHS initiative to sequence the entire genomes of 100,000 people by 2017 began. The project, run by the newly founded Genomics England, represents one of the largest genome sequencing projects to ever be attempted.

One of the key focuses of the project is to target rare genetic disease. By comparing the genetic code of people with rare conditions against unaffected controls it is hoped that new genetic variation will be identified that can cause disease. “We expect those with undiagnosed genetic conditions to be one of the primary beneficiaries of large scale genomic projects” says Mr. Meade.

It could be a long road ahead though. Although it is now relatively cheap and quick to gather sequence information, analysis to find causative gene variants requires sophisticated computing and can be a time-consuming, complex process.

It is not just ambitious projects such as Genomics England that can offer hope. “Access to diagnostic tools and services in the NHS can also improve. We still see members being diagnosed when they finally get to see the appropriate expert.” Mr. Meade adds.

Generalising the requirements of as diverse a group as SWAN patients is predictably difficult. However a common need identified by SWAN UK has been to put members in contact with one another. “SWAN UK is described by many of our members as a life line, somewhere where others truly understand” says Ms. Roberts.

SWAN UK is a fantastic charity, and is very successful in assisting its members in overcoming the isolation and difficulties they can experience in coming to terms with having the diagnosis of an unknown condition. However there is significantly more that needs to be done by policymakers in creating needs based rather than disease based support services for the families of these children. It is a tragedy of policy when those who genuinely need support are stuck in limbo of box ticking bureaucracy.




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