Sophie, a 15-year-old, is brought to the emergency department by her parents after a two-week history of progressively worsening breathlessness. She is now unable to manage even the short walk to school without stopping for rest.
Whilst speaking to her, you find out that she was recently diagnosed with Loeys-Dietz Syndrome and is awaiting an elective aortic root replacement. Her current symptoms, however, are not entirely new. Her parents recall episodes of cyanosis in infancy and exertional breathlessness throughout childhood, which were often dismissed or put down to other things.
At the bedside, Sophie describes sudden episodes of palpitations, dizziness on standing, and intermittent chest tightness.
You’ve not heard of Loeyz-Dietz Syndrome before, and so once you’ve organised an ECG, chest x-ray and bloods for Sophie, you open your computer to do some reading.
Understanding rare diseases
Rare diseases, by definition, affect fewer than 1 in 2,000 people in the UK. But while each condition might be uncommon, the challenges they bring are all too familiar — diagnostic delays, under-recognition, and a lack of standardised treatment pathways. These hurdles aren’t just clinical; they ripple into the psychological and ethical care of patients and families.
In this post, we’re focusing on one such condition: Loeys-Dietz Syndrome (LDS), a rare connective tissue disorder with significant cardiovascular implications and a requirement for lifelong, multidisciplinary care.
Loeys-Diez Syndrome
Loeys-Dietz Syndrome (LDS) is a rare multisystem connective tissue disorder, first recognised in 2005.[2] It’s caused by mutations in genes involved in the TGF-β (transforming growth factor-beta) signalling pathway — most commonly TGFBR1, TGFBR2, SMAD3, TGFB2, or TGFB3. These mutations disrupt normal connective tissue development and remodelling, leading to a broad spectrum of clinical features.
Children with LDS may present with skeletal differences such as scoliosis, pectus carinatum, joint laxity, or contractures. But it’s the cardiovascular complications that often raise the highest concern — including aortic aneurysms, dissections, and valvular abnormalities.
There is no definitive cure for LDS, and management focuses on treating complications as they arise. This includes procedures such as aortic root replacement, heart valve surgery, and orthopaedic surgeries, including scoliosis correction and knee replacements, which may be required during adolescence.
The Diagnostic Odyssey
Loeys-Dietz Syndrome can be tricky to spot. It often gets mislabelled as Marfan Syndrome or Ehlers-Danlos Syndrome, thanks to overlapping features like joint hypermobility, skeletal differences, and vascular concerns. But LDS tends to take a more aggressive course. Aortic aneurysms and dissections can occur at much younger ages – sometimes even in childhood.
The statistics are sobering: the average age of death in LDS is just 26.1 years, with aortic dissection as a leading cause. That’s why early diagnosis matters. Regular imaging, including echocardiograms and arterial imaging, is essential for detecting aneurysms early and guiding timely intervention.
Delays in diagnosing Loeys-Dietz Syndrome don’t just mean a missed label – they mean missed chances to prevent life-threatening complications. A retrospective study found that patients diagnosed before their first surgery had significantly better outcomes than those diagnosed afterwards.
Without a timely diagnosis, children may not be referred to the right specialists – genetic counsellors, cardiologists, vascular surgeons – and key elements of management can fall through the cracks. Given the rapid and serious progression of LDS-related complications, early identification is more than helpful; it’s life-saving.
Misdiagnosis isn’t the only challenge — where a child lives can also shape their diagnostic journey. Families in rural or resource-limited settings often face additional hurdles, including limited access to specialist services, longer travel times to testing centres, and a general lack of awareness about rare conditions among local healthcare providers.
The England Rare Diseases Action Plan 2025 recognises these barriers, especially when it comes to accessing genomic testing — a key part of diagnosing conditions like LDS.[5] Bridging these gaps will require not just improved services, but better education and outreach to support clinicians working outside major centres.
It’s not just patients who feel the distance. Clinicians in rural areas may also struggle to access genetic expertise. A recent systematic review found that healthcare professionals working outside major centres often have fewer established relationships with genetic specialists, making it harder to get timely advice or referrals.
For many families, the path to a diagnosis of Loeys-Dietz Syndrome is long and winding – often spanning years of unanswered questions, repeated referrals, inconclusive tests, and misinformation. This prolonged diagnostic odyssey can delay treatment, allowing the disease to progress unchecked.
But the impact isn’t just medical. The uncertainty takes a toll – emotionally, psychologically, and financially. Parents are left navigating a system that feels fragmented, while their child’s symptoms persist or worsen.
All of this underscores the need for earlier recognition, better access to genetic testing, and truly integrated multidisciplinary care. An early, accurate diagnosis doesn’t just open doors to treatment — it also brings clarity, helps families plan, and eases the distress that comes with not knowing.
A breakdown in trust between patients and their clinicians
Communication between doctor and patient becomes even more critical in the context of rare diseases, where patients often rely solely on medical professionals for answers. Uncertainty from healthcare providers is understandable – but if not handled with care, it can erode trust, lead to confusion, and leave families feeling lost in the system. Open, honest, and compassionate conversations help build the therapeutic relationships that are so crucial in managing complex, lifelong conditions like Loeys-Dietz Syndrome.
Miscommunication often stems from a lack of specialist input. According to a 2020 survey by the National Organization for Rare Disorders (NORD), 1 in 5 patients with a rare disease wasn’t being managed by a specialist at all.
This isn’t necessarily due to a lack of effort — but rather a reflection of how tough it can be for generalist clinicians to build confidence in managing conditions they may only see once in a career. Limited exposure, referral barriers, and uncertainty about who to involve all contribute to this.
Add to that the patchy training on rare diseases and a lack of accessible, up-to-date clinical guidelines, and it’s no wonder families often feel they’re the ones holding the knowledge. Improving access to specialist care – whether through outreach, virtual MDTs, or clearer referral pathways – is crucial.
As a result, patients often become ‘experts’ in their own conditions, relying heavily on self-advocacy to navigate research and healthcare services. Add the fact that our healthcare culture associates uncertainty with failure, discouraging clinicians from openly discussing uncertainties with patients, and it becomes clear how the gap can widen. Reduced communication about symptoms and treatment options weakens shared decision-making and layers mistrust onto a somewhat fragile relationship. Acknowledging diagnostic uncertainty is crucial for establishing trust and promoting the development of more effective detection strategies.
Lack of standardised guidelines
Even when national guidelines exist, they can fall short in practice. For rare conditions like Loeys-Dietz Syndrome, guidance is often based on limited evidence – case reports, small cohort studies, or expert consensus – rather than large, high-quality trials.
That doesn’t render the guidelines useless, but it does make them more challenging to apply at the bedside. Without detailed, practical recommendations, clinicians can be left wondering how best to adapt generic advice to the complex realities of individual patients. This can stall decision-making, delay referrals, and leave families feeling uncertain about their care.
Looking specifically at Loeys-Dietz Syndrome, one of the biggest challenges in management is its phenotypic heterogeneity. The condition can present with a wide range of features and varying severity, even within the same family.
This makes a ‘one-size-fits-all’ approach unrealistic. While guidelines exist, they must remain flexible to accommodate individual variation. However, for clinicians unfamiliar with LDS, this flexibility can feel more like ambiguity, making decision-making more challenging and increasing reliance on specialist input.
More explicit guidance on when to escalate, refer, or monitor could help bridge this gap — especially for paediatricians and generalists who may be the first to spot a red flag.
Even among specialists, there’s still no clear consensus on some key aspects of Loeys-Dietz Syndrome management. Take aortic surgery, for example: while Marfan syndrome has well-established thresholds for prophylactic repair, LDS is more aggressive — and that’s led some teams to recommend earlier intervention, even at smaller aortic diameters.
But surgical thresholds vary between centres, and without unified guidelines, this inconsistency can leave both clinicians and families uncertain about the best course of action. Managing risk is often as much about expert judgement as it is about numbers.
Living in a remote village in Cornwall meant Sophie faced numerous challenges both before and after her diagnosis with Loeys-Dietz syndrome. Limited access to specialist care, coupled with local doctors dismissing her symptoms, meant that by the time she was diagnosed, her condition had progressed significantly, requiring multiple surgeries.
Alongside her physical challenges, Sophie struggled with her mental health. The rarity of her condition left her without peers who could relate to her experience, contributing to feelings of isolation and low self-esteem during adolescence. Eventually, she accessed psychological support and began therapy, which helped her accept her condition and develop coping strategies.
The Ethics of Rare Disorders
Rare diseases often sit on the periphery of research, education, and policy — receiving only a fraction of the attention given to more common conditions. The result? Systemic inequities in access to diagnostics, specialist care, and treatment, especially for those living in rural or economically disadvantaged areas.
When children face delayed diagnoses or miss out on life-saving interventions simply because of where they live, the ethical principle of justice is compromised. Access to care shouldn’t depend on geography — yet for many families navigating rare conditions, it still does.
It’s not just ethically correct to improve care for children with rare diseases — it’s a legal obligation. Under the Health and Social Care Act 2012, NHS bodies are required to reduce health inequalities. That includes making sure patients with rare conditions aren’t disadvantaged by postcode or poor service availability.
The Human Rights Act 1998 supports this. Article 14 prohibits discrimination in the enjoyment of healthcare rights, and when systemic barriers disproportionately affect people with rare diseases, it may amount to indirect discrimination.
Health Literacy
Health literacy is a critical — but often overlooked — factor influencing health outcomes. In the absence of widespread clinical expertise, families affected by rare diseases are often forced to become their own experts. Some can navigate medical literature, question treatment plans, and advocate for their child. But doing so requires a high level of health literacy and digital competence.
For others, the picture is very different. Limited health literacy can make it harder to interpret complex medical language, judge the credibility of online information, or participate meaningfully in shared decision-making — all of which can contribute to poorer outcomes.
This brings us to a key ethical concern: autonomy. Informed consent and shared decision-making are foundational to good care — but they can’t happen if patients and families are overwhelmed, misinformed, or unable to process complex medical information.
The legal standard set by Montgomery v Lanarkshire Health Board [2015] is clear: patients must be informed of all material risks in a way they can understand and use to make decisions.[24] If we don’t support families in building health literacy, we’re not just risking miscommunication — we’re failing to meet both our legal and ethical obligations.
Respecting autonomy means ensuring that every family has the tools, time, and support necessary to be true partners in their care.
Modern healthcare rightly promotes self-management and patient empowerment, particularly for individuals with chronic and rare conditions. While this aligns with the ethical principle of autonomy, it can also place an unfair burden on patients and families — particularly those already navigating systemic barriers.
When care pathways are unclear and support is patchy, asking patients to manage complex conditions on their own risks doing harm. This sits uncomfortably with the principle of non-maleficence. Poorly supported self-management can lead to delays in care, inappropriate treatment, worsening anxiety, and a breakdown of trust in the system.
Improving patient care in Loeys-Dietz Syndrome
In Loeys-Dietz Syndrome, early diagnosis isn’t just ideal — it’s critical. Identifying the condition early enables proper risk stratification, regular cardiovascular surveillance, and timely surgical intervention when necessary.
Early detection starts with vigilance and screening — especially in families with a known history of connective tissue disorders. Key strategies include:
- Genetic testing for individuals with a family history of LDS or suggestive features
- CT or MRI angiography of the full arterial tree to identify atypical or distal aneurysms
- Paediatric screening, particularly in at-risk children, to initiate surveillance and preventative care early
These tools, when used proactively, can dramatically shift outcomes — transforming high-risk situations into well-managed ones.
The Welsh Rare Diseases Action Plan (2022–2026) outlines a clear framework for enhancing care for individuals with rare conditions — with education at the forefront.
One of its key priorities is integrating education on rare diseases into both undergraduate medical curricula and ongoing professional development. The goal? To equip clinicians with the knowledge and confidence to recognise rare conditions earlier, make appropriate referrals, and reduce delays in diagnosis.
By raising awareness and building expertise at every level of the healthcare system, the plan aims to shift outcomes — and experiences — for children and families navigating rare diseases like Loeys-Dietz Syndrome.
The Welsh Rare Diseases Action Plan also tackles one of the biggest challenges in rare disease care: coordination across the multidisciplinary team. To address this, the plan recommends assigning a named consultant for each patient — someone who acts as the central point of contact and care coordination.[28]
This lead clinician helps bring together the wider team — from cardiologists and geneticists to orthopaedic surgeons and mental health professionals — ensuring that care is integrated, consistent, and tailored to the individual.
For complex conditions like Loeys-Dietz Syndrome, where no single speciality can manage everything alone, this kind of structured coordination makes a real difference to both outcomes and family experience.
Finally, the plan recognises that where a patient lives shouldn’t determine how they’re cared for. To address geographic disparities, particularly in rural and remote areas, the plan advocates for practical solutions such as telemedicine, mobile clinics, and investment in local healthcare services.
These initiatives aim to make specialist input more accessible, reduce the burden of travel, and ensure that patients with rare diseases receive high-quality care regardless of postcode.
Sophie’s journey highlights that rare diseases carry not only complex medical needs but also a profound emotional burden, especially when care pathways are unclear and social support is limited. Integrating mental health care and peer support into the management of rare diseases is essential, especially for patients in socially or geographically isolated communities.
The takeaways
Rare diseases like Loeys-Dietz Syndrome highlight clinical, ethical, and systemic gaps that traditional healthcare models are not designed to handle alone. They demand flexible, integrated, and patient-centred approaches across every level of care.
When diagnostic delays, fragmented communication, and lack of coordinated care collide, the result is avoidable harm — both physical and psychological. Families can feel isolated, unheard, and let down by a system that’s meant to support them.
Improving health literacy, accelerating diagnosis, and embedding rare disease care into policy, education, and everyday clinical practice isn’t a luxury — it’s a necessity. These are the foundations of an equitable, ethical, and compassionate healthcare system.
References
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