It has taken 13 years for my son’s ultra rare genetic medical condition to be diagnosed. Unfortunately for many parents and carers, they’ll never receive a diagnosis and that must be one of the hardest things to come to terms with. For others they may not be aware that it is now possible to have their whole genome sequenced for genetic conditions which previously would have gone undiagnosed.
I always knew my infant son had developmental delay: he was slow to talk; slow to reach milestones; had unusual behaviours; and then the sucker punch that I didn’t see coming – epilepsy. And this wasn’t the one-off infantile spasms of early childhood, but relentless, unremitting seizures, which kept coming at any time of the day or night. There were absence seizures where my son would blank out for a few seconds; myoclonic seizures where his body and arms would jerk upwards and forwards, knocking him off his feet; focal seizures where his body would contort into odd movements and behaviours, leaving him desperately distressed; and, finally, tonic-clonic seizures, stiffening and shaking his 2 year old body and which wouldn’t stop until you had to administer rescue medication or in desperation call for the ambulance. Our son would have hundreds of different types of seizures a day, so we had no choice but to add more and more anti-epileptic drugs until he was little more than a dribbling zombie, staring blankly at the wall whilst CBeebies played in the background. And yet the seizures continued.
Diagnosis?
He was given many diagnoses and prognoses in his first seven years. We were told he would never speak, he would need a wheelchair, he would be profoundly disabled. Most were devastating and, in retrospect, blatantly incorrect. And throughout his early years there was an ongoing discussion – or rather an assumption – that he was autistic. We weren’t convinced and thought it was more complicated than that; so we in turn were labelled as being ‘in denial’.
Then, aged 7, the neurologists at Great Ormond Street Hospital (GOSH) told us he most probably had some kind of genetic or metabolic condition; and the GOSH neurodevelopmental assessment unit tested and evaluated him as not being autistic. At that point, I started looking elsewhere for answers. I did my research and found the Deciphering Developmental Disorders (DDD) genetic study1 and, much to the surprise of the local geneticist, asked for my son to be part of it. They agreed and he – and we – provided DNA samples to be tested. My son would never have had this opportunity if his diagnosis had stopped at ‘autism with epilepsy’.
And then we waited…and waited …and eventually….gave up waiting and hoping for a diagnosis and got on living our life as best we could without the support we needed.
And then one day—five years later!—a letter dropped through the door: DDD had found the genetic problem; they had an answer for us. Apprehensively we attended the geneticist appointment to be told our son had an epileptic encephalopathy caused by a deletion on the CHD2 gene. But what did this mean? What was his prognosis? Where was his support? And where was ours? We had lots of questions but there were few answers.
But, at the time, we left the room feeling happy and thankful that we had a diagnosis – hopeful that this was going to be the start of a whole new chapter where we could now improve the quality of our son’s life.
We had also been given the name of a Facebook group supporting CHD2 parents, which we of course immediately joined. It was a small group in 2017, set up by other parents of children with CHD2, and we did the best to support each other with the basic knowledge we shared and the information we gleaned from a couple of research papers. Bit by bit as a group of pro-active parents we pieced together CHD2’s primary characteristics. A prognosis was more elusive as almost everyone who had received the diagnosis was still a child.
Support from the NHS?
But where was the provision to help patients and caregivers of those affected with one of these new rare genetic diagnoses? Almost 70 new, rare and ultra-rare genetic conditions had been discovered – what support had been put in place to help people cope with this new knowledge and these new conditions?
The NHS did the best it could with the resources it had. But the neurologists, the paediatricians, the nurses, the therapists and all the other professionals had as little – or less – knowledge than the parents and carers of those children with the newly diagnosed genetic conditions. When there are only a handful of people in the entire country who have got CHD2 – or any other ultra-rare condition – what are the chances that your neurologist has ever seen a case before, or even heard of the condition? Virtually none.
And sometimes it was hard to get these busy NHS professionals to pool their knowledge or to reach out to others. From our own enquiries, we advised our neurologist that one of their colleagues in a regional centre 100 miles away had written a research paper on the condition and likely knew as much about it as anyone in the country. Our neurologist seemed unwilling to pick up the phone to contact him, so in the end we contacted him ourselves.
Don’t get me wrong: we were thankful for the genetic diagnosis, but then there was little support or advice from the health service on how to deal with such a rare condition. And as you would expect, education, social care and other support organisations likewise didn’t know of or understand the condition and were unable to provide the high level of support needed.
This problem must have affected thousands of children and their families as a result of receiving their new genetic diagnoses. It was a remarkable achievement to set up the genetic testing regime for countless families with undiagnosed conditions; but then, having revealed many new diagnoses and discovered new conditions, there was very little in place to guide and support those families.
Even today, where are the lead specialists for each rare and ultra-rare genetic condition? It seems entirely random as to whether an individual neurologist or clinician takes an interest in a particular condition, rather than there being a systematic attempt to harness the manpower of the NHS and engage specialists for each known condition.
And where are the specialist genetic centres that cater not only for a person’s epilepsy condition but holistically for the wide range of difficulties that often follow?
If we could set up several regional or national centres, they could each focus on a number of rare conditions. The patients, parents and carers would receive better support and treatment; the medical professionals would see more examples of the conditions; outlook and prognosis would certainly improve for many; and pressure would be taken off other clinics and professionals in the NHS.
As things stand, it can seem like the rarer the condition, the less support is available. We want to change that.
CHD2-related disorders currently have just over 300 people diagnosed worldwide. In the USA, work done voluntarily by parents through the original CHD2 parent-led Facebook group has grown into the dynamic “Coalition to Cure CHD2” charity, which is now fundraising and championing high level research aiming for a cure.
And we hope to achieve something similar here in the UK. We have recently set up an unfunded, parent-led, CHD2 UK group. It currently has almost 40 families registered, mainly from the original Facebook group. But I am certain there are more families out there. And though the number of CHD2 patients appears small in isolation, there are many other rare conditions with similar numbers; put together, there is a significant need to be met. We need funding, a lead neurologist, a lead paediatric neurologist, associated specialists, and a centre of excellence – not just for CHD2 but for all the ultra-rare genetic conditions recently diagnosed.
Between the years of 2010 – 2023, 67 new ultra-rare genetic conditions such as CHD2 were discovered via DDD and, later, the 100,000-genome project2 in the UK and Ireland. Over 13,000 families participated in the DDD Study and 5,500 received diagnoses; and this number is still increasing. With a little more foresight, these projects could have argued for, and secured, further funding to coordinate support for those individuals whom they diagnosed. After all, you wouldn’t diagnose cancer and then leave it to be treated by someone who had never heard of cancer before – so why do that for ultra-rare genetic conditions?
These projects were hailed as a huge success – and in many ways they were, particularly for the research community – but were they a success for those who were diagnosed? Certainly they now had a name for their condition…but what next?
The undiagnosed
And, perhaps more worryingly, how many people are there who have never had the chance to take part in whole genome sequencing? How many adults have CHD2, for instance, but have never been tested and have no idea what their diagnosis is? How many have been labelled as ‘autistic with epilepsy’ and written off?
A few years ago, I was out one day with my son queueing for a canal boat trip and a mother with her daughter recognised my son as having learning disabilities. She asked me what diagnosis my son had and I told her: CHD2 Epileptic Encephalopathy and associated learning disability, autistic features, language and communication issues, sensory problems and demand avoidance.
I asked her about her adult daughter and she replied briefly, “She is autistic with epilepsy.” For a moment her comment jolted me right back to those early years struggling to find a diagnosis. I asked her if she had ever thought about turning that diagnosis around and considering whether her daughter had a genetic condition where epilepsy was one of the defining characteristics and autism one of the consequences. It was as if a light switched on and this was the first time she had been presented with this possibility. She left with the intention of enquiring with her GP about the possibility of having her daughter’s entire genome sequenced.
How many more learning-disabled adults are out there who, prior to the DDD project, have been misdiagnosed and overlooked and who actually have a rare or ultra rare genetic condition but may never get the opportunity to find out?
If we hadn’t questioned our son’s ‘autism with epilepsy’ diagnosis, we would never have researched and explored the other possibilities. I would still be worried and fearing for his future, I wouldn’t have knowledge of the latest medical treatments, the possibility of a future cure, and the support and empathy of other parents. Even more importantly is the reassurance of knowing, thanks to other parents, that there are adults with CHD2 who are now starting to live a fulfilling adult life. My son, now aged 20, is one of them.
Further information and useful links:
https://www.ddduk.org/further-information/
- The Deciphering Developmental Disorders (DDD) Study 2010
More than 13,500 families from 24 regional genetics services across the UK and Ireland were recruited to the Deciphering Developmental Disorders (DDD) study, a collaboration between the NHS and the Wellcome Sanger Institute.
All the families had children with a severe developmental disorder, which was undiagnosed despite prior testing through their national health service and likely to be caused by a single genetic change. The Wellcome Sanger Institute sequenced all the genes in the children’s and parents’ genomes to look for answers, a search which is still ongoing.
https://www.ddduk.org/ ↩︎ - 100,000 Genome Project – The 100,000 Genomes Project launched in 2012 to sequence 100,000 genomes from patients with cancer and rare disease in order to drive the integration of genomics into UK healthcare.
https://www.genomicsengland.co.uk/initiatives/100000-genomes-project ↩︎
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