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events page. See you in Chicago.
This is Laura Dierda with the Becker's Healthcare
Podcast. I'm thrilled today to be joined by
doctor Paul Kruska, who's a clinical geneticist at
Children's National Hospital in Washington, DC. Doctor Kruska,
it's a pleasure to have you on the
podcast today.
Yes. Thank you for having me. I really
appreciate it.
Now I'm looking forward to our discussion. I
know there's so much happening in the health
care space and in particular
in, genomic testing, just really a fast moving
field. But before we dive into the broader
questions, can you tell us a little bit
more about yourself and your background?
Yes.
I'm a physician,
and I'm board certified in clinical genetics. This
is a specialty that I find a lot
of people don't know much about. We're a
we're a small specialty, and
and what we do is we diagnose
and treat a large portion of rare diseases.
I spend most of my time as chief
medical officer at a company called GeneX. We
do commercial testing,
and I'm also a
faculty member at Children's National Medical Center where
I teach genetic residents, the next generation of
clinical
geneticists.
And prior to GeneDx, I spent over a
decade as a physician scientist researching rare diseases
at the National Human Genome Research
Institute, and that's one of the institutes
National Institutes of Health in Bethesda, Maryland.
So, really, my my professional career centered around
helping families
and patients affected by rare disease.
That sounds like a fascinating role to play.
And given your experience, what are some of
the key developments in genomic testing over the
last 5 years or so?
Yes. The the the last the the last
5 years have been fantastic
for,
for genetic testing and and really,
for patients and and their families.
And
the the biggest change in the last 5
years has been a dramatic shift to broad
based testing
with whole exome sequencing and whole genome
sequencing.
For your listeners not familiar with these tests,
whole genome sequencing
sequences our entire genetic code, if you can
believe it. It's all 33,000,000,000
base pairs of DNA,
our our our genetic code. And whole exome
sequencing
focuses on the exome, which consists of the
protein coding regions of the genome, and this
is about 2% of our genome.
Most disease causing variation
in clinical genetics and genetic diseases occurs in
the exome.
But as we learn more about variation outside
of these protein coding regions, whole genome sequencing
is becoming increasingly more important. So really
exciting,
shift. And and there's there's
a number of reasons for this shift to
the broad based,
testing.
And the most important piece is that clinical
studies
clinical evidence
shows a higher diagnostic
yield for whole genome sequencing and whole exome
sequencing over other types of testing, such as
multi gene panels and chromosomal microarray.
Another big reason for the shift is professional
organizations such as the one I belong to,
the American College of Medical Genetics and Genomics,
are recommending that clinicians use whole exome sequencing
and whole genome sequencing as a first tier
test for
conditions such as developmental delay,
intellectual disability, congenital anomalies, and epilepsy.
And, 3rd, health insurance companies are starting to
pay for this.
Both public and private
payers are starting to reimburse for coxumecipacine
and whole genome sequencing. Matter of fact, 90%
of commercial payers
are paying for whole exome and whole genome.
So this is huge.
And then last,
which is is is also
related to to the payers, that the technology
is improving and the cost of these technologies
are dropping.
So exome and sequencing,
whole exome sequencing, and whole genome sequencing prices
are are dropping. So this is this testing
is becoming more accessible.
That's great to hear. You know, I'm really,
fascinating
that these tests are becoming more accessible,
and people's ability to really know more about
themselves and and prepare as well. I can
imagine it is really beneficial.
What do pediatricians
need to understand about the advantages of some
of this advanced
genomic testing versus other categories of genetic testing?
Yes.
They need to know a lot. So that's
the the the short answer. The the long
answer is,
I want I wanna group these
these tests into 3 buckets. So first, I've
already talked about broad based testing, whole exome
sequencing, and whole genome sequencing. So let's put
that in one bucket.
And and and both of these tests,
as I noted,
covers our entire genome. So we have 20,000
genes, so it covers all of that. Now
bucket number 2 are multi gene panels, and
these test 100 of genes or less.
And this was very popular,
in in the past, you know, in the
past 10 years because it was less expensive
than doing the whole genome or whole exome.
So second bucket, like I said, are multi
gene panel. And then the 3rd group is
something called chromosomal microarray,
and this was being developed back when I
was a a medical
school student and and resident in training, many
years ago. And this looks for large duplications
and deletions of our genes in our in
our genome, often involving millions of base pairs
of of DNA. So that's the 3rd bucket.
And so all 3 of these buckets are
being used today.
And what the pediatrician needs to know,
and this is the most important
fact that they need to know, is that
the diagnostic yield is significantly higher for exome
and genome than the other types of testing,
which makes sense as as exomes and genomes
are are much more comprehensive.
And rare disease discovery
continues to progress at a very high rate.
There's hundreds of new gene disease associations
every
year. So you can imagine that these panels
just can't get big enough to include all
these different genes. So broad based testing is
able to capture these new discoveries where a
panel is limited to
the genes that were originally placed on the
panel. And then there's microarray, the 3rd bucket,
and this looks for
large
duplications or deletions of our genome.
And we're talking about millions of base pairs
and hundreds of genes often needs deletions.
But, really, we want the resolution down to
a single base pair or single alphabet of
our genome, and that's where
whole exome sequencing and whole genome sequencing
really puts the bill. It gets right down
to single base pair changes along with what
microarray does anyway. So this broad based testing
is much more efficient, and it's better for
patients and their families because
they get a diagnosis
quicker. Many many clinicians today are doing what
we call serial testing. They'll start out with
a chromosomal microarray, then it move to a
multi gene panel. Then finally, they'll get around
to broad based testing with whole exome sequencing
or whole genome sequencing.
And this delays the diagnosis as I mentioned.
And also, it incurs unnecessary
medical costs. So just,
the medical
associations
and the payers are definitely pointing to what
the medical evidence says. Let's go straight to
broad based testing.
That's great to hear. You know, and really
powerful information for physicians and pediatricians in particular
is they're looking at how they can advise
their patients, see what really the next steps
are moving forward.
Now I'm wondering too, what are some of
the barriers to patient and provider access to
the advanced, genomic testing, and what steps need
to be taken in order to increase that
access?
Access to a medical provider who can order
and diagnose a rare condition is the biggest
barrier in my opinion.
There are very few medical geneticists in this
country. And as I said in the introduction,
I'm a medical geneticist.
And
we, the medical geneticists, are the main state
for ordering genetic testing in North America.
A recent report by the National Academies of
Sciences, Engineering, and Medicine on pediatric subspecialties
reported that clinical geneticists
and of all other specialists
to be seen.
In my experience,
it is not unusual
to wait 1 year for a referral to
a clinical geneticist.
This simply is unacceptable
for patients to have to wait that long
and families. This this prolongs their suffering, but
also strains an already stretched health system.
There's also low uptake and understanding from non
geneticists
less familiar with advanced genomic testing such as
whole exome sequencing and whole genome sequencing.
As guidelines
and coverage continue to increase pointing to the
critical role of these tests in pediatric care,
I really want to see more non geneticists
like pediatricians
embracing these tests as a standard of care.
And until we get to that point, there's
gonna be long waiting
lines
or for patients and families to get this
type of testing and a precision diagnosis.
Another barrier is patient and family awareness about
genomic testing. I've spoken to many families with
conditions such as epilepsy or autism
that wish they had known about genetic testing
years before they received the diagnosis.
It's well known that less than 1 in
6 parents or 15%
of parents of undiagnosed
children
have
heard of or are familiar with advanced testing
such as whole exome sequencing or whole genome
sequencing.
So these this lack of awareness
testing is is really the number one barrier.
And I I don't I don't wanna skip
over commercial insurers and payers. Well, 90% of
commercial
insurers
pay for this type of testing. As I
mentioned before,
in 28 states
cover whole genome sequencing or whole exome sequencing
through state Medicaid programs,
our payer system is still not perfect. And
there's certainly a lot of opportunity with payers
to improve re the reimbursement process and make
it easier for ordering providers to to order
these tests.
That's such a great point. You know that,
kind of closing the gap with the number
of providers
and specialists who are are doing these tests
plus making sure there's access from insurance and,
from that perspective is so crucial.
Looking ahead, what's on the horizon for genomic
medicine? What do you really see over the
next few years?
Yeah. That's that's something I love to talk
about. I I teach medical students,
here in the Washington DC area, and what
I tell them is
my
specialty or or my career with the diagnosis,
and their career is gonna be in treatment.
We are really in the golden age
of genomic medicine right now with all these
new treatments and improved testing such as whole
exome and whole sequencing. So we're really in
an an exciting
time going forward.
What I see on the horizon
is eliminating the diagnostic odyssey. So there's there's
a term we use a lot, and I
might have mentioned it earlier
in this podcast. But the diagnostic odyssey is
the time when symptoms begin
until a diagnosis is made.
And in rare disease, it averages about 6
years.
And I don't think any of us in
the cyst in the ecosystem and the rare
disease
ecosystem
should sleep until this time is much shorter.
6 years is too long
to to have a diagnosis. So as we
move forward,
for both children and adults,
the horizon
is in the future, is gonna show a
decrease in the diagnostic odyssey. And there's a
lot of reasons for this. One is is
we've talked about in this this podcast that
improved,
access to whole exome and whole c whole
genome sequencing.
Another part that that's really gonna decrease the
diagnostic odyssey
is moving testing earlier in people's lives.
I wanna talk just briefly about this project
that's called, the Guardian Project. And there's other
projects like this
around the world right now. And this is
where we
expand newborn screening to diagnose
more rare diseases
earlier and presumably healthy
infants before
symptoms set in and and and cause harm
to to these infants. And there's a there's
really an exciting project
that is taking place in New York City
through Columbia University,
the New York State Health Department,
and,
GNDX, the the company where I spend a
lot of time. And we're newborn
screening newborn screening traditional newborn screening that's supplemented
with whole genome sequencing technology.
And this program has sequenced over 10,000
babies in New York City.
And a test for an additional 450
rare disease conditions
that are actionable.
And so you can imagine instead of diagnosing
a child who has suffered 10 years without
knowing to diagnosis, you're diagnosing
these conditions in infancy.
And like I said, over 10,000 infants have
been completed. We're seeing a diagnostic yield about
3%. So 3% of individuals are getting the
test, and the consent rate is surprisingly high.
This is a research project,
through Columbia University in in New York City,
and the the consent rate is over 70%.
So this is really fantastic. This is an
example
of diagnosing
rare disease
earlier in in in cutting out that diagnostic
odyssey. And then there's a lot of other
really exciting things that that are happening in
in North America.
A lot of neonatal intensive care units or
NICUs are starting to do what we call
rapid whole genome sequencing in the NICUs where
we have critically ill infants,
and they're doing testing.
And it gives these these infants
a diagnosis and allows for a precision therapy.
So
moving the needle earlier and earlier,
is gonna be extremely helpful. And I and
as we move forward in the next 5
years, you're gonna see a lot of these
earlier testing,
programs implemented.
So this is this these are some of
the the things that I see on the
horizon.
And and then the last thing is is
what we talked about before, I think.
Pediatricians
and non geneticists are gonna take the the
baton from geneticists and and really
decrease those long waiting
lines
for for,
care and testing.
That's fascinating. Doctor Kruska, thank you so much
for joining us on the podcast today. This
is a really informative and interesting discussion, and
I look forward to connecting with you again
soon.
Yes. Thank you for having me, and and
I I really enjoyed speaking and and and
really wanna get the word out about the
diagnostic odyssey is alive and well at 6
years, and and we really we really need
to to make that smaller.