Any day now, Lexi Robins will be taking her first wobbly steps. But while most mothers greet this milestone with pride, Lexi’s mother Alex is absolutely dreading the moment.
Her one-year-old has a rare genetic condition where knocks and bumps can trigger a terrifying process in which her body begins to turn its own soft tissue, such as muscle, into hard bone — ultimately creating a second skeleton.
Thought to be one of the rarest and most disabling conditions known to medicine, fibrodysplasia ossificans progressiva (FOP) causes a lattice of bone to grow throughout the body, gradually paralysing the person, joint by joint.
There is no cure, and patients deteriorate gradually. Often they will be in a wheelchair by their 20s and may struggle to eat and drink if bone growth causes their jaws to lock.
Thought to be one of the rarest and most disabling conditions known to medicine, fibrodysplasia ossificans progressiva (FOP) causes a lattice of bone to grow throughout the body, gradually paralysing the person, joint by joint
Around one in three develops partial or full hearing loss because of the fusion of bones in their ears. Others find the extra bone growth around their ribcage restricts their breathing, making them prone to infections. Most FOP patients die prematurely, in their 40s and 50s.
‘We are very anxious about Lexi becoming mobile,’ says Alex, 30, an events manager. ‘We’ll always be on edge, with eyes in the back of our heads.
‘She’s a happy, sassy little girl who always wants to copy her older brother Ronnie. He’s a boisterous three-year-old — but he doesn’t have FOP and accidents happen.
‘It’s a fine balance between allowing Lexi to develop normally and keeping her safe. Our biggest fear is her falling over.’
In preparation for Lexi taking her first steps, Alex and her husband David, 39, a sales manager, have covered every sharp corner or ledge in their home with padding to cushion future bumps. They’re also selling their forever home — a ‘higgledy-piggledy’ four-bedroom cottage in Hemel Hempstead — to move into a bungalow or a flat.
‘We planned to grow old here — but it’s much more important to keep Lexi safe,’ says Alex.
Eventually, they plan to build a bungalow customised to Lexi’s needs, including wide doorways (to reduce the chance of bumps) and no steps — and they intend to keep her at home rather than send her to nursery.
FOP, which is diagnosed via a genetic test, affects around 60 people in the UK, or one in a million. It is individually rare, but there are more than 7,000 known rare conditions, and approximately 80 per cent of these are linked to genes, says Samantha Barber, CEO of the charity Gene People.
In fact, rare diseases affect one in 17 people in the UK, and 75 per cent of these diseases affect children.
FOP is caused by the mutation of a gene called ACVR1, which helps to control the growth of new bone. This mutation usually happens randomly rather than being passed on. However, if someone is born with the mutation, there is a 50 per cent chance they will pass it on.
‘With FOP, any fall or bump can stimulate the faulty ACVR1 receptors present in all cells, triggering the production of bone in areas of soft tissue, such as muscles and ligaments,’ says Professor Richard Keen, a consultant in metabolic bone disease at the Royal National Orthopaedic Hospital in London, and a specialist in FOP.
‘Surgical removal is not an option because this would cause more trauma, and as a result, more bone growth.’
There is no cure, and patients deteriorate gradually. Often they will be in a wheelchair by their 20s and may struggle to eat and drink if bone growth causes their jaws to lock
For while a fall can be the trigger for someone with FOP, actually any sort of trauma, such as surgery, dental treatments or intramuscular injections, can do the same, which is why many with the condition considered it too dangerous to have Covid jabs, for instance.
‘Live viruses, such as the flu, can also cause problems, as the virus can prime the body’s immune system and precipitate a flare-up,’ says Professor Keen.
Helen Bedford-Gay’s 13-year-old son Oliver has FOP. ‘Despite a person’s best efforts, flare-ups can, and do, occur spontaneously,’ she says. ‘One of the hardest aspects of living with this condition is the uncertainty.’
Helen, 47, a primary school teacher and trustee of the charity FOP Friends, says that when Oliver was two, for example, he woke one morning with a golf ball-size lump on his neck. ‘There had been no warning the night before, it just appeared,’ she says.
While there is no treatment for FOP, symptoms can be managed; steroids can be prescribed for short-term pain relief and to reduce swelling.
Oral prednisolone, a steroid medication, reduced the swelling on Oliver’s neck and he didn’t lose movement in his jaw, as his parents had feared. But otherwise there is no effective way to stop the progress of bone growth, says Professor Keen.
Even securing a diagnosis is very difficult. ‘For many people with rare conditions such as FOP it can take years because doctors haven’t come across them,’ says Samantha Barber. ‘Misdiagnosis can lead to patients undergoing treatments they not only don’t need but which may also be harmful.’
The lumps produced by FOP flare-ups can be misdiagnosed as cancer, for instance, and treated with unnecessary chemotherapy, as Rachel Winnard, 37, knows from bitter experience.
Rachel, who was born with FOP and lives in Rochdale, Lancashire, experienced recurring flare-ups on her neck and chest as a child. These were misdiagnosed as aggressive fibromatosis — a benign but prolific non-cancerous tumour — and treated with several rounds of chemotherapy from when she was 19 months old to the age of 12.
One bout of chemotherapy aimed at curing a flare-up caused by banging her back on a swing, aged nine, was particularly gruelling.
‘I was really poorly,’ says Rachel. ‘I was constantly sick and couldn’t eat.’ She lost weight and her hair fell out — only for more lumps to appear on her back the same night. This time, doctors switched her to radiotherapy.
She was finally diagnosed with FOP aged 12, by a doctor who recognised her symptoms, having recently read about the condition (the ACVR1 gene had not yet been identified so no genetic test was available).
Following several bad falls, over the years Rachel’s mobility has reduced. Now she’s reliant on her family to care for her, needing an electric wheelchair to get about.
Yet, determined to get on and enjoy life, she opted to have the Covid jab in her immobilised right arm so she can travel abroad — risking causing trauma in that arm and worsening FOP. Thankfully, she did not have a flare-up after the jab. Cases such as Rachel’s underline the importance of early diagnosis, says Professor Keen.
‘Early diagnosis enables parents to help their children avoid accidents and potentially risky medical procedures — for instance, asking for childhood vaccinations to be administered subcutaneously rather than into a muscle.’
(For reasons which are still unclear, FOP flare-ups seem to be triggered by injury to deep tissues and not to the skin. It also appears that some muscles, such as the diaphragm, eye muscles and tongue, aren’t affected, while legs and arms are.)
Most patients with rare conditions such as FOP can suffer for years before securing a diagnosis, but fortunately Lexi was only five months old, thanks partly to Alex’s tenacity but also because of increased awareness of FOP, the availability of information online and access to genetic testing.
As a second-time mother, it was quickly clear to Alex that ‘something wasn’t quite right’, despite Lexi passing all the standard post-natal checks.
‘Her big toes were bent inwards and there was something odd about the movement of her fingers,’ says Alex. She took Lexi back to hospital where she was examined by a paediatrician, who thought she had been born with bunions.
Further X-rays showed Lexi had no knuckles in her thumbs or big toes — a characteristic of FOP.
‘We were told she might never walk and that she might have a “syndrome” of some sort, and we were referred to an orthopaedic specialist,’ says Alex. Meanwhile, online research led Alex to the FOP Friends charity website.
She says she ‘knew immediately’ she’d found the answer after reading about the characteristic formation of toes and fingers in those with FOP, and recognised Lexi’s symptoms.
‘It was horrendous. I couldn’t stop crying,’ says Alex. ‘I was heartbroken to know that Lexi’s life would be cut short and that she would be paralysed in her own body.’
Armed with knowledge of the necessary tests, the family got a formal diagnosis after consulting a private paediatrician.
Since then, Alex and David have thrown their energy into helping raise awareness of the condition along with vital funds for research into a potential cure.
And there are good grounds for optimism. At the end of last year, MPs voted to consider funding research into a potential treatment for FOP, after a petition organised by FOP Friends gathered more than the required 100,000 signatures.
Clinical trials are under way for two medicines which may help to treat the condition by blocking the bone growth process, says Professor Keen, who hopes a treatment could be available imminently.
‘It won’t be a cure but it will be a major breakthrough if these drugs can be shown to slow the process,’ he says. ‘It would mean, for instance, that in future we could operate to remove excess bone growth which is locking someone’s jaw, without risking causing further trauma.’
One of these medicines, palovarotene, was originally developed to treat the lung condition chronic obstructive pulmonary disease and has recently been approved for treatment of FOP in Canada. It’s expected the data from a trial will now be examined by the UK health watchdog, the Medicines and Healthcare products Regulatory Agency, later this year, hopefully leading to it getting the green light to be used to treat FOP here.
In trials, researchers found palovarotene appeared to block the bone growth process if taken daily, with higher doses administered for 12-week periods if a flare-up occurs.
There is hope for another drug, too: saracatinib, originally developed as a cancer drug. It is also thought to block bone growth in FOP.
A study is under way at the Royal National Orthopaedic Hospital, as well as in centres in Holland and Germany.
One challenge, however, is the small pool of people available for trials. Another is that such drugs could be most effective in children — ‘because the potential benefit is greater, as FOP is not so far advanced’, explains Professor Keen.
‘But you have to balance this against the ethics of giving a drug to a child when you don’t know if it will work or what the side-effects may be.’
And there is also the hope that a drug developed to treat FOP might have potential wider uses, too.
For instance, a rare childhood brain cancer is associated with the same ACVR1 gene, so it’s thought that a drug which interferes with the pathway by which this operates could potentially have a use for treating this cancer, subject to trials.
Meanwhile, raising awareness of the condition is key to ensuring those affected can live as fulfilling a life as possible.
‘People with FOP are spirited individuals who make the most of their lives; they can go to university, have jobs and lead fulfilling lives, though they may need help as their condition progresses,’ says Professor Keen.
Samantha Barber adds: ‘These advances are great news for those affected by FOP — and also for the wider rare disease community, as every element of new knowledge has ripple effects, showing new perspectives on conditions.
‘Each discovery is a further step in our understanding of these conditions — and frankly knowledge is key for patients and their families who are affected by them.’
How unusual medical discoveries were made. This week: The nostril is the most painful place to be stung
When a bee sting to the testicles didn’t hurt as much as anticipated, insect specialist Dr Michael Smith, now at Auburn University in Alabama, decided to find out the most painful area to be stung — using his own body.
For 38 days he triggered stings by pressing a bee against different body parts, then rated how much they hurt. The three most painful areas were the nostril, the upper lip, and the penis shaft, while the skull, middle toe tip, and upper arm were the least painful, he wrote in the journal PeerJ.
His theory is that the nostril may have a lower threshold for triggering pain so it can alert us to anything entering the body.