From the moment Sasha was born at home in Nottingham, her parents Lisa and Mat Gapp where aware that their first child had some differences.
But it was only after many years of living with a “Syndrome Without A Name” and seemingly endless questions before the family received an answer through the 100,000 Genomes Project.
At first there was nothing to suggest anything out of the ordinary. “Pregnancy was fine” recalls Lisa. “Sasha was our first child, so we didn’t know what to expect. The morning after Sasha was born the paediatrician came to see us and noted some things that were unusual about Sasha, such as dysmorphic facial features”.
“Sasha also had a few other differences at birth, such as open marks on her head” adds Mat. But it was when Sasha stopped breathing at four days old that Mat and Lisa realised something was wrong. “We went back into hospital but they couldn't find a reason as to why she stopped breathing” says Lisa. Despite a week in hospital undergoing a battery of tests including x-rays, blood tests, skin biopsies, and a lumbar puncture, nothing was found to give Mat and Lisa any answers to their daughter’s condition.
At around 6 weeks Lisa says they started to notice some differences in Sasha compared to other children her age.
“Sasha wasn't looking at us, she wasn't really engaging. Her eyes still looked like those of a young baby, like they were glazed and not really responding to us”. Sasha continued to miss developmental milestones as she got older but still her parents had no clues as to why this was happening.
On the road to answers
It was around 2007 that the family was put under the care of Dr Nora Shannon, Consultant Clinical Geneticist at Nottingham University Hospitals NHS Trust.
Lisa recalls: “Every time we saw Dr Shannon we would turn up with a list of things that we had Googled and we’d ask ‘do you think Sasha has this?’”.
Mat continues: “We wondered if it might be Pseudopseudohypoparathyroidism or Prader-Willi Syndrome. We really wanted to find answers for Sasha”.
“Dr Shannon was very good with us” continues Lisa. “Telling us that she didn’t think it would be this or that. She was very tolerant of all our questions! So for a long time Sasha was a swan”.
By swan Lisa means that Shasha’s was a “Syndrome Without A Name” (SWAN). And it was through Rare Disease Charity SWAN UK that Lisa and Mat found support and community though connecting with other families affected by an undiagnosed rare condition or disease.
We met a lot of friends through SWAN. It was good to get support and advice from other families who were in our position and facing the decisions that we were facing. For example, we got great support and advice from the SWAN community over whether to leave Sasha in mainstream school or transfer her to a special school. Because the developmental gaps between Sasha and her peers were getting bigger and bigger”.Lisa Gapp, Sasha's mum.
“The contacts and friendships we made through SWAN were really important to us” adds Mat.
Around 2017 Dr Shannon made Mat and Lisa aware of a research study called the 100,000 Genomes Project.
“Everyone knew we were keen to get a diagnosis” says Lisa. “To help with planning for the future, and just to put our minds at rest that hopefully Sasha didn’t have anything that was too serious or would limit her life”.
“And we wanted to help with the research side of things as well” adds Mat. “To add to the knowledge base so other families in future might be able to get a quicker diagnosis. We knew first-hand what it was like to live with uncertainty and lots of questions”.
Despite having lived for just over 11 years with a Syndrome Without A Name, the family had to wait 3 more years for their result.
“It was quite a long time before we received Sasha’s genetic diagnosis” explains Lisa. “We were on holiday in France in 2019 when we got a call from Dr. Shannon who said “we have a diagnosis”. It was a big shock to us, because we’d resigned ourselves to the idea that we might never find out what Sasha had”.
Whole Genome Sequencing (WGS) revealed that Sasha has Xia-Gibbs Syndrome. The Syndrome was discovered by a US research team headed by Professor Richard Gibbs, who found that it arises from mutations in the AHDC1 gene. Professor Gibbs was inspired by his niece, Molly, the first child to ever be diagnosed with Xia-Gibbs Syndrome, partly named after her uncle who was determined to find out what lay behind his niece’s unknown condition.
As a neurodevelopmental disorder, it originates in the brain, causing physical and intellectual disability. The Syndrome appears in the first year of life, as it did with Sasha, usually in the form of hypotonia (poor muscle tone), sleep apnea and poor feeding. Developmental and language delays follow, and older children experience intellectual disability and are sometimes classified with symptoms of autism spectrum disorders (ASDs).
There is never a family history, so there is usually a ‘diagnostic odyssey’. Many families search for years before finding the cause of their loved one’s symptoms, receiving misinformation and inadequate care along the way. This is why…building awareness and collaboration between families and scientists…is so important.From the Xia-Gibbs Society website
This certainly describes the experience of Lisa and Mat. But finally getting a genetic diagnosis for Sasha was, as Lisa explains “a massive relief. We’d done so much research into so many conditions and syndromes, and many of them would have meant that Sasha might have a shorter life expectancy. But with Xia-Gibbs there doesn't seem to be any medical issues as far as shortened life expectancy is concerned”.
Lisa and Mat continue to benefit from connecting with other families whose lives are touched by a rare condition or disease. “We’ve made connections with support groups around the world. It's been a real help to find that Sasha isn't the only one” reflects Lisa.
“Having people to talk to that have the same experiences has been so helpful” agrees Mat. And Lisa adds “It's difficult with any child who has special needs. But I think having people with similar experiences has helped us a lot. But it works both ways too. There are a lot of younger children out there. And with Sasha one of the older children diagnosed in the UK, we can answer a lot of their questions”.
While only a handful of children have been diagnosed with Xia-Gibbs Syndrome in the UK, due to their own ‘diagnostic odyssey’ over many years Lisa and Matt suspect that many more remain undiagnosed.
“Every month five or six people are welcomed into the worldwide Xia-Gibbs community. There must be around 400 now. But I think a lot of children with autism and ADHD are probably not going to get tested for a Syndrome like this. It does make you wonder how many other children have it.”
Dr Nora Shannon, Consultant Clinical Geneticist at Nottingham University Hospitals NHS Trust said: “Sasha’s story illustrates how important a diagnosis is to a family in terms of information, support, prognosis and planning. Her 13 year diagnostic journey spanned several advances in genetic testing but ultimately it was Whole Genome Sequencing which lead to the answer".
The introduction of whole genome sequencing in the NHS is helping to give a diagnosis in many families at an earlier stage.Dr Nora Shannon, Consultant Clinical Geneticist at NUH
Today Sasha is excited about her hair appointment (she’s getting pink highlights) and enjoys life and hobbies such as gymnastics, swimming, baking and playing Uno with her mum and dad (Sasha won twice in a row during our interview). But as Lisa explains, she does have her challenges too.
“Sasha has always struggled with certain behaviours. I think it's a frustration thing with not being able to express her feelings and struggling verbally.”
As with so many parents of children with a very rare condition, Lisa and Mat are finding new things about Sasha all the time, but their message to others in a similar position is to keep asking questions.
There are lots of things on our radar that we're concerned about. Epilepsy, Scoliosis, ADHD. But it's okay to go back to your clinical geneticist or paediatrician and ask “is this OK? Is this consistent with the Syndrome?Lisa Gapp
Despite the occasional challenges associated with Sasha’s condition, Lisa and Mat are immensely proud of their eldest child: “We know we are very lucky to have Sasha” beams Lisa. “She is a fantastic, bubbly, happy girl who loves to socialise and have fun”.
Useful links and resources for patients and the public
Useful links and resources for healthcare staff
- National Genomic Test Directory (see Part III)
- Requesting whole genome sequencing: information for clinicians - Genomics Education Programme
- East Genomic Test Order Forms (for staff in the East Midlands and East of England)
- Resources to support healthcare staff