Ana Lisa Tavares: Genomics 101 - What is a rare condition?

In this explainer episode, we’ve asked Ana Lisa Tavares, Clinical
Lead for rare disease research at Genomics England, to explain
what a rare condition is, in less than 10 minutes.


You can also find a series of short videos explaining some of the
common terms you might encounter about genomics on
our YouTube channel


If you’ve got any questions, or have any other topics you’d like
us to explain, feel free to contact us
on info@genomicsengland.co.uk.


Want to find out more? Check out the blog 'Genomics 101: What is
a rare condition?'


You can download the transcript or read it below.


Naimah: What is a rare condition? Today I’m joined by Ana Lisa
Tavares, Clinical Lead for rare disease research at Genomics
England, and she’s going to explain more.


Ana Lisa: There are thousands of rare conditions. I hesitate to
say a number as we’re learning all the time, so this keeps
changing. There are estimated to be perhaps around 10,000
different rare conditions, as an order of magnitude. Many rare
conditions start in childhood, 75% or three quarters affect
children. A little over 10% affect adults, only adults, and some,
around 20% can start in children or adults.


Naimah: So, what makes a condition rare?


Ana Lisa: A rare condition can be defined as affecting less than
one in 2,000 people in the general population. This is a
definition that’s used in Europe. Different parts of the world
use slightly different numbers and definitions, so for example,
the number of people with a rare condition living in that
country, there isn’t one single universal definition.


The important part I think is that this is a practical way to
help shine a spotlight on rare conditions, which collectively
affect a lot of people, and the particular challenges in making
diagnoses and finding treatments for rare conditions. So
together, it’s estimated 7% of people are affected by a rare
disease in their lifetime, or one in 17, so that means that there
are 3 and a half million people in the UK affected by a rare
disease, and in the world, probably somewhere between 250 to 450
million people, so perhaps 350 million people, a really huge
number.


When you look into these numbers, there are rare conditions that
are much more common than others. So, 80% of people with a rare
condition have one of the 150 most commonly occurring rare
conditions. Cystic fibrosis would be an example that many people
will have heard of, and if you look at those numbers from a
different angle, 85% of rare conditions affect less than one in a
million people, so are very rare, and it’s important to bring
together these different voices to solve some of the common
challenges.


Naimah: Can you explain to me how these differ from more common
conditions?


Ana Lisa: The simplest answer is that they are defined by the
frequency, so how often they happen in the general population,
and one reason for grouping together thousands of rare conditions
is to highlight some of the particular challenges. This includes
delays in getting a correct diagnosis that can often take years,
an increased chance of a misdiagnosis before getting to an
accurate diagnosis, and treatment challenges, as 95% of rare
conditions don’t have a specific treatment. This is a very good
question, and I would like to note that it’s also an artificial
distinction to some extent. So, human conditions have a range of
underlying causes that can be broadly grouped together, including
genetic and environmental, such as a viral infection.


However, it gets complicated, for example, a proportion of common
conditions that may have many different causes will have a
genetic component, so for example causing an early onset familial
form of a condition, such as diabetes. And in fact, genetic
causes may give or can give the clue or the key that’s necessary
to develop a new drug therapy that can then help many people with
the condition, so those that may have a rare genetic cause and
those that have a more common cause, such as for high
cholesterol.


So, one other way that rare and common conditions can differ, not
just based on frequency, is the causes of those rare conditions
and common conditions. I’ll start by saying that there are lots
of rare conditions that aren’t genetic, and there are common
conditions that do have a genetic basis, so none of these
observations are absolute, but there’s a spectrum of different
causes for rare and common conditions. So, I would say there are
more rare conditions that are caused by a single genetic cause,
and there are more common conditions that might be caused by many
very small genetic effects acting together, and also many
different environmental causes.


Naimah: So, are rare conditions always genetic?


Ana Lisa: The short answer is no. Many rare conditions do have a
genetic cause, perhaps 70 to 80% of rare conditions, so if you
had 10 people with different rare conditions together in a room,
the chances are that 8 of them will have a genetic component to
their rare condition. And when we talk about genetic causes,
these can of course be very varied, from a single letter change
in the DNA code to an extra chromosome with several hundred
genes. Rare conditions include ones without any known genetic
cause, so for example some rare infectious diseases and some rare
cancers. And I think it’s important to say that there’s a lot
that we collectively don’t know yet about rare conditions, so our
understanding is incomplete and imperfect, and there’s still a
huge amount to understand.


Naimah: And it would be good to understand what challenges
patients with rare conditions might face.


Ana Lisa: There are many challenges in achieving an accurate
diagnosis, getting well organised, coordinated care, and the fact
that 95% of rare conditions don’t have a specific treatment.
There’s a big impact on emotional wellbeing for those with rare
conditions and their parents and carers. Genomic Alliance did a
survey showing that 88% of those with a rare condition felt
emotionally exhausted from having their rare condition, and there
are big impacts on other aspects, such as education, employment,
etc. 


Naimah: And what do you think the future looks like for the
treatment of patients with rare conditions?


Ana Lisa: So, this is a huge question with many answers. I think
key is coordinated care, and I’m personally really excited about
the potential for new rare therapies to be made for particular
types of genetic causes that perhaps one day could be modified to
treat many different types of rare conditions. To me, this would
be incredibly powerful and would be a dream to transform
therapies for rare conditions.


Naimah: That was Ana Lisa Tavares explaining what a rare
condition is. I’ve been your host, Naimah Callachand, and if you
want to hear more explainer episodes like this, you can find them
on our website at www.genomicsengland.co.uk. Thank you for
listening.