The impact of a genetic diagnosis

Deciphering developmental disorders (DDD) is an exciting new project run by the Sanger Institute in partnership with NHS genetics clinics. It aims to use sequencing and microarray analysis to diagnose children with developmental problems.

I was struck by the impact a diagnosis has on the families involved and was drawn to a quote on the project’s home page from Beverly Searle, CEO of Unique (Rare Chromosome Disorder Group):

Over many years I have witnessed the frustration and heartache of many families for whom a reason for their child's developmental delay has not been found....more recently I have been delighted to see the relief and joy of other families on receiving a diagnosis

I asked Beverly if she could suggest someone to talk to and she put me in touch with Jane Gregory, whose daughter Chrissy was diagnosed using microarray analysis. Here is our conversation:

Tell me about Chrissy

We didn’t know anything was wrong at first but in hindsight the signs were there at the start. Chrissy’s suck was weak, she vomited up all her feeds and did not gain a healthy amount of weight. Her head was floppy and her developmental milestones were late. She started having epileptic seizures at about ten months and terrible head-banging screaming outbursts.

There was a gradual realisation that something was wrong, I kept badgering our doctors but they treated me like a neurotic first-time mum. My fears intensified when I compared Chrissy to other babies of the same age, and realised how far behind she was. However no one took my fears seriously until I was pregnant with my son when Chrissy was about a year and had started having epileptic seizures. Initially I thought the long difficult birth had caused Chrissy’s problems then I wondered if the whooping cough vaccine had contributed.

Chrissy is now 27 and has moderate/severe learning disabilities, epilepsy, severe autism (only diagnosed five years ago, coincidentally - the same year as the chromosome abnormality was found) and challenging behaviour. She also has days where she is absolutely adorable, funny, affectionate and compliant. She is in an independent hospital funded by the NHS for assessment and treatment to try to stabilise her moods and find a better treatment regime. She comes home every weekend.

How did the array analysis happen and what did you learn?

The array analysis came out of the blue. Chrissy had been seen regularly by geneticists at Great Ormond Street and when she was 14 they asked if we wanted to take part in a research study looking at the ends of chromosomes in people with unexplained learning disabilities. Nothing was found and we forgot all about it. I tried to come to terms with the fact that we would probably never know the cause of Chrissy’s problems.

When Chrissy was 22 I received a letter out of the blue from Great Ormond Street. It said that our DNA had been tested for another research project, also looking at unexplained learning disability, this time using different technology – microarray analysis. An anomaly was found (1q21.1 microdeletion) and it was thought to be significant enough to be the cause of Chrissy’s problems.

How did you feel when you found out?

At first I was thrilled because I had been searching for answers for years. Then, when the implications sunk in, I was concerned that it may be hereditary and wanted to know if future generations were at risk. It turns out that the microdeletion was de novo – spontaneous. Mine and Chrissy’s dad’s DNA were normal.

What has been the impact of the results?

The results and the autism diagnosis have changed the way that I see the future. The two are interchangeable in some ways. Now I can finally tell people why Chrissy is like she is – “She has autism and a rare chromosome disorder”. It helps me to be able to explain it and people ‘get it.’

I think it has given us more leverage to get the services Chrissy needs. Health professionals accept that people with a rare chromosome disorder can be very complex but we have had a huge battle to get Chrissy into hospital. I have battled for services throughout Chrissy’s life and it is exhausting and demoralising at times. Three local authorities have been rowing over funding for Chrissy’s care for about three years now and I have recently made a formal complaint.

Knowing that Chrissy has autism has helped us to support her more effectively. We know that 1q21.1 can be associated with heart and other organ defects. We were able to get Chrissy checked and, thankfully, she is fine.

It is hard not to dwell on how much easier our lives would have been if the cause of her problems had been found when she was little. I had a book published about our experiences ‘Bringing Up a Challenging Child at Home’ and had articles published about different issues we’ve faced over the years in the Daily Mail, Woman’s Weekly and Woman among others.

Have you made any connections with other families with similar disorders?

I have made lots of connections through Unique and on Facebook. There is a Facebook group for 1q21.1 microdeletion. I have also made connections with other families affected by different rare chromosome disorders.

It would have been such a relief to have been able to do that when Chrissy was little. There is a particularly wide range of effects for people with 1q21.1 microdeletion – some people present with no problems at all, others, like Chrissy are more severe, but there are some characteristics shared by many - neuro-psychiatric and behavioural problems, autism and feeding problems in infancy.

Why do you think these kinds of studies are important?

These studies are important because a diagnosis or cause for a child’s problems can make a big difference for families. I felt terribly isolated when Chrissy was a child and even felt out on a limb among other families that had learning disabled children. Some of them were judgemental about Chrissy’s challenging behaviour.

I felt stigmatised, as if I were to blame, and felt that I’d failed as a parent. I didn’t get the support I needed until I had a breakdown when Chrissy was six, and thereafter services were patchy, particularly when we moved to different areas. Having a medical label or a cause for your child’s problems helps families to access support and health services much earlier.

Psychologically, if I had known what was wrong, I wouldn’t have felt like such a bad parent or devoted so much time and energy searching for answers or cures. (An example is the gluten and casein free diet that caused Chrissy to become anorexic.) I believe that I would have enjoyed Chrissy and her siblings more and the effects on the family may have been less drastic. Chrissy’s siblings had to grow up too quickly and saw their older sister have prolonged violent self-harming outbursts that their distressed mum didn’t have enough anything like enough support to cope with.

Also, very importantly, if parents are carriers of a chromosome abnormality, they need to know, as it has huge implications for the health of their other children and wider family. I believe that in situations like ours everything needs to be done to pinpoint a cause. I remember Chrissy’s GP saying “a diagnosis wouldn’t change anything.” I hope GPs and other health professionals are educated in the importance of a diagnosis these days!

Is there anything else you would like to add?

After years of searching for answers, to the point of obsession, the results of the microarray test changed our lives. Further research into these rare conditions continues and I hope that we will eventually gain more insight into Chrissy’s genetic disorder and be able to offer more effective support and interventions. She is the oldest person diagnosed with 1q21.1 micro-deletion as far as I know, and the more we learn about Chrissy the more info, help and support we can offer families with younger children who face similar problems.

Mefford, H. et al (2008). Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric Phenotypes New England Journal of Medicine, 359 (16), 1685-1699 DOI: 10.1056/NEJMoa0805384

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