Penicuik siblings with rare chromosome disorder seek database match

The couple had suffered a string of miscarriages which genetic testing eventually linked to a chromosomal flaw carried by Mrs Arnott, known as a "balanced translocation".

Normal human cells contain 23 pairs of chromosomes each made up of two strands of DNA, one inherited from our mother and one from our father.

In a balanced translocation, a section of genetic material switches places between chromosomes.

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Although normally harmless, it can lead to problems conceiving and increases the risk of an "unbalanced translocation" in offspring - meaning they have duplicate or missing pieces of chromosome which can lead to learning disabilities, developmental delays and health problems.

Genetic testing after Lily was born established that she had an extra chromosome strand - in additional to the 46 strands which normally make up the 23 pairs - which comprised a large section of her maternal chromosome 21 and a shorter portion of the maternal chromosome 18.

Her younger brother, Benjamin, three, has the same unusual arrangement which has so far not been identified in any other patients whose details are logged with UK or international databases.

Although it shares some similarities to Down's Syndrome, where people carry three copies of chromosome 21, the extra portion of DNA found in the Arnotts' children is not the part considered critical for causing the associated medical problems, such as hearing loss and early-onset dementia, and medics can offer little guidance on how their conditions might progress.

"Our children don't have any of the facial features of Down's," said Mr Arnott, who is 42 and originally from Glasgow.

"They're taking them down the medical pathway as if it was Down's but they're on a bit of a wing and a prayer, because it's an information vacuum. They just don't know.

"Both our children have developmental delay. They don't speak - or they speak one or two words.

"My five and a half year old has just finished primary one and she's still in nappies. She has hypermobility so she gets very sore joints.

"They both still use pushchairs, and my son gets a lot of chest infections - he's hospitalised with croup all the time."

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The Arnotts are among 684 families in Scotland who have signed up with Surrey-based charity, Unique, whose world-leading database helps to track down and pair families with extremely rare chromosome and gene disorders in the UK or overseas.

Mr Arnott, a global business development manager for a hospitality firm, said finding a match "would be huge".

"We don't have anything to gauge our children against," he said. "If you had another family it would give you a better idea of what the milestones might be, because - whatever the milestones might be for a 'normal' child - they went out the window pretty early for us.

"My children didn't walk until they were two and a half, they didn't roll over until they were nearly 18 months."

Unique was founded in 1984 by Edna Knight after two of her four daughters were born with a rare chromosomal disorder characterised by a partial duplication of a section of chromosome nine.

Unique CEO, Beverly Searle

Doctors knew of no other recorded cases but, through word of mouth, Ms Knight tracked down four other families whose children had the same abnormality and they formed an ad hoc support group, writing letters to one another to share their experience.

In 1990 it expanded to include other genetic and chromosomal abnormalities and, in 1993, became an official charity.

Advances in genomic sequencing mean that around one in 100 births are now identified as having rare chromosomal disorders, compared to one in 200 around 20 years ago.

The technique mirrors that used to track the emergence of new variants of the coronavirus behind Covid, but instead unpicks the DNA of children with suspected medical or developmental abnormalities.

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Beverly Searle, CEO of Unique and a former microbial genetics researcher, first became involved in 1990 after her daughter Jenny was born with profound disabilities and medical problems due to a chromosome abnormality.

She said: "We're very fortunate in the UK to have this fantastic new genomic medicine service now where they can do the most up to date DNA sequencing.

"It's advanced incredibly, so they can find the tiniest, tiniest changes in a single gene - even a single letter change.

"When my daughter was born all you could do was look down a microscope at stained chromosomes, so you had to have really big losses or gains or rearrangements of chromosomal material to spot that there was an issue.

"Now, with DNA sequencing, at least 40 per cent of those kids get diagnoses and as we refine the technique, you'll get more and more diagnoses.

"So for many families we're overturning this really terrible diagnostic obstacle that many of the families used to be on, just trying to find 'why is our child like this? Did we do something wrong?'.

"Of course they did nothing wrong - it's just that their particular chromosome or genetic disorder couldn't be picked up by the technology before."

To learn more about Unique and its database, visit www.rarechromo.org.