EU definition – less than 1 in 2000 people affected. But at least 7000 described. So prob 3.5 million in the UK, and lifetime risk 1 in 17?
Most present in childhood. And 30% will die before age 5…
9 rare diseases tested for at birth so drop in the ocean… Some US states test over 45…
Average delay in diagnosis in UK patients is 5.6 years, with average of 4 different primary care and 4 secondary care clinicians! https://globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf
Dare to think rare!
Common challenges –
- Misdiagnosis
- Inappropriate treatment
- Passing between specialties
- Having lived experience denied or not listened to
- Then having to become advocates +/- carer
- Diagnostic criteria can be unclear
- Stigma – outward appearance or misconceptions
- Cf invisible conditions – “doesn’t look disabled”
- Poor coordination of care. Role of primary care unclear.
- “Burden of explanation” and lack of knowledge in professionals
- Transition
- Guilt (where genetic)
- Mental health (chronic illness or underlying disease)
Diagnostic “odyssey” – unfathomable obstacles. Often labelled functional (or worse…), and parents as “anxious”, “demanding”.
Doctors tend to force a common diagnosis on to symptoms/signs that don’t quite fit.
Parents struggling with a sick child may delay having other children, may spend out on private treatment or move to different areas/countries to seek care, lose earnings/educational attainment, and family relationships suffer.
Once diagnosis is made, life begins with health issues being only 1 part of the whole picture rather than defining life. And provides access to experts and family support all over the world.
Become expert patients/families. Patient organisations offer support but also advocacy, research
No treatment is not no management
Not knowing the condition doesn’t mean you can’t listen and try to understand, or that you can’t coordinate things (esp when multiple teams/professionals involved).
Some will be happy to disclose/discuss diagnosis – others may get bored and frustrated at times – and may be stigma
Primary care and emergency departments gain very little confidence. Hospital staff involved in ongoing care still only considered to be knowledgable by about 40%!
Health care teams need to monitor research landscape.
Diagnosis
“Dare to think rare” – medical education tends to stifling curiosity. Proformas and pathways as a hindrance to rare conditions.
Eg crushing chest pain in 40yr old slim female – spontaneous coronay artery dissection!
GENES –
- Group of congenital anomalies – 1 is common, 2+ less so
- Extreme/exceptional presentation of common condition – eg infection, or child presentation of something seen normally in adults
- Neurodevelopmental delay/regression – “bad behaviour”?
- Extreme/exceptional pathology
- Surprising lab results
History – trying not to ignore anything. 3 generation family history. Pregnancy loss; disability.
“THINK AND” – many stories of diagnosis only being made when someone listens to whole story from beginning to end. Parental concerns AND multisystem problems AND family history AND disability… Example of Alstrom syndrome – visual impairment then obesity, then heart failure.
“THINK AGAIN” – beware diagnostic bias of having a diagnosis from the past or from another doctor. “Momentum bias” – diagnosis might start as tenuous but become entrenched. “Premature closure” – thinking stops when diagnosis accepted (even if not verified). New test available to confirm?
Open access tools – www.FindZebra.com, OMIM, Orphanet. Only Google after trying these! Start with 2 most specific (stand out) terms. [Phenomizer appears to be defunct]. Mendelian – AI tool in development.
NHS is at forefront of genomic medicine (whole genome analysis rather than panels of tests) – 100 000 genomes of people with rare disease and cancer analysed. Approx 1 in 4 rare disease patients have had useful (“actionable”) results.
Phenotypes are helpful but same pathway can be affected by different mutations and same phenotype can be seen in different conditions.
Microarray vs gene panel vs whole exome (coding only) vs whole genome…
Hope is for quicker diagnosis, less tests, less inappropriate treatment, support family planning decisions, enhance research.
National Genomic Test directory – https://www.england.nhs.uk/publication/national-genomic-test-directories/
Downside is variants of uncertain significance… https://vimeo.com/451887065
[Medics 4 Rare Diseases]