Primary Ciliary Dyskinesia (PCD)
Genetic Testing
patient guide
What is Primary Ciliary Dyskinesia (PCD)?
PCD (formerly called immotile cilia syndrome) is a genetic condition
that can affect the lungs and other parts of the body. The condition is
caused by cilia that are not working properly. Cilia are tiny, hair-like
structures that line many of the tissues in our body, including inside our
lungs. These cilia all “beat” in time with each other, in order to move
mucus and debris out of our respiratory system. This is especially
important for breathing and preventing infections.
The cilia “beat” in unison, which helps to
move debris and mucus out of the lungs
Mucus and
debris
Cilia
Cells line
the inside of
the lungs
In people with PCD, the cilia may be formed differently, or don’t beat
together as well. This causes mucus and debris to build up in the lungs.
This can lead to breathing problems and frequent infections.
When the cilia do
not beat in unison,
mucus and debris
can collect inside
the lungs making it
harder to get out
What is Kartagener Syndrome?
Kartagener syndrome is a condition that fits within PCD. It involves
PCD and a medical condition called situs inversus. Situs inversus means
that a person’s internal organs are shifted to opposite places than usual
in their body, like an exact mirror image. That means their heart is on
their right side instead of their left side, their liver is on their left side
instead of their right side, and so on. Usually, this shift of all the organs
does not cause any health problems by itself. Situs inversus can occur in
anyone, including people who do not have PCD. About half of people
with PCD have situs inversus.
how organs are usually
placed in our bodies
Right Lung
how organs are placed in people
with kartegener syndrome
Left Lung
R Lung
Stomach
Heart
Liver
Heart
Spleen
Liver
In a smaller number of people with PCD, their organs may be shifted
from their usual position, but not in an exact mirror image. The medical
term for this is situs ambiguous. In people with situs ambiguous, some
organs may be shifted, but others may not be. This means their positions
relative to each other are different, and this can sometimes cause
medical problems. Sometimes the organ shifts may be mild and not
cause additional health concerns. In other situations, the organ shifts can
be severe and cause significant health problems (like with development
of the heart).
What Causes PCD?
PCD is genetic, which means it is inherited through a person’s genes.
Genes have instructions for how our bodies work and develop. Everyone
has two copies of each gene. We get one copy of each gene from each
of our parents. Mutations (changes in the gene, like spelling mistakes)
in certain genes can cause PCD. Most times, if someone has two
mutations in a PCD gene, he or she can have PCD. If someone has one
mutation in a PCD gene, he or she is called a “carrier” and usually does
not have symptoms of PCD. Anyone can be a PCD carrier, and not
realize it. If both parents are PCD carriers, there is a 25% chance they
can have a son or daughter with PCD together.
There are also very rare cases where PCD can be caused by one gene mutation, usually passed
from a mother to an affected son. More details about this are on page 5.
How Likely is it that Genetic Testing Will Find a Mutation?
If you (or your child) has PCD, there is a 60-65% chance that our
genetic testing will find the gene mutation(s) causing it. Not every PCD
gene is known or understood at this point in time. With further
research, the chances of finding a mutation may be better in the future.
For a complete list of genes and references, visit ambrygen.com
notes
Is PCD Genetic Testing Right for Me?
Genetic testing for PCD can sometimes confirm a diagnosis to make sure
medical care is appropriate. This testing may also help find family
members who have a chance to have PCD themselves, or those who might
have a child with PCD. However, learning information from genetic testing
can cause worry and anxiety for some. Please talk to your doctor or
genetic counselor about any questions or concerns you have during the
process. While many issues are reviewed in this booklet, this information
is meant to add to a talk you have with your doctor or genetic counselor.
What Happens if I Test Positive for Gene Mutations?
If your testing shows you have two gene mutations, this may confirm a
diagnosis of PCD in you. The picture below shows how people usually
carry and pass on mutations in PCD genes.
Most people who carry a mutation in only one copy of a PCD gene are
called “carriers,” and do not usually have symptoms. If their partner is
also a carrier of a mutation in the same gene, there is a 1 in 4 (25%)
chance for them to have a son or daughter with PCD in each pregnancy
together. There is a 2 in 4 (50%) chance for them to have a child who is a
PCD carrier (usually without symptoms), and a 1 in 4 (25%) chance for
them to have a child who does not have PCD, and is not a PCD carrier.
PCD carrier (one gene mutation)
Does not have PCD, and not a PCD
carrier (no gene mutations)
Has PCD (two gene mutations)
Rarely, PCD can occur when only one gene mutation is present, usually passed down from a
carrier mother to her son. Your doctor or genetic counselor can explain this type of inheritance
further, if it applies to your family.
What Should I Tell My Family Members About PCD?
If you have one or two mutations in a PCD gene, it is possible that other
people in your family may also be carriers of PCD or have PCD. If they
wish, they can have testing to see if they have any of the same
mutations found in you.
What Do My Results Mean?
If you have genetic testing, you will receive one of four possible results in
your test report: positive, carrier, negative, or inconclusive (“variant of
unknown significance” or VUS). Below are explanations of these results,
which you should discuss with your doctor or genetic counselor.
results
explanation
Positive
• Two mutations* were found in a PCD gene
• This may confirm a diagnosis of PCD in you. Your doctor will
discuss any treatment options with you.
• More testing may be needed (usually of your parents, if
possible) to better understand what your result means.
• Your adult family members can now be tested for the same
mutation(s), if they would like.
Carrier
• One mutation was found in a PCD gene*
• You will likely not have symptoms of PCD. Some carriers may
have mild symptoms.
• You have a chance to have a child with PCD if your partner is
also a carrier.
• Your partner, and other adults in your family, may wish to be
tested for the same mutation.
Negative
• Your testing did not find mutations in any PCD genes included
in the test. If you have been diagnosed with PCD, that remains
the same
• You may still have a mutation in a different gene or for a
different condition not included in this test. Talk with your
doctor or genetic counselor about whether more genetic
testing is right for you.
Inconclusive • A change (like a VUS) in a PCD gene was found, but we do
not know if it causes PCD or not
• Testing other family members may help to understand the
VUS.
• Talk with your doctor or genetic counselor about whether
more genetic testing is right for you or your family.
• A VUS can sometimes become understood after more
research is done. Keeping in touch with your doctor or genetic
counselor can help keep you updated.
* Very rarely, PCD may be caused by only one mutation in a PCD gene. Your healthcare provider
can explain more about this type of inheritance to you.
Common Questions About Genetic Testing
q1. how does genetic testing work?
Genetic testing is done using a blood or saliva sample (other sample
types may also be used – please see ambrygen.com for details). Your
sample is sent overnight in a special kit to Ambry (all organized by your
doctor or genetic counselor). Once your sample and paperwork arrive
at Ambry, your testing begins. Results will be sent to your doctor or
genetic counselor, who will talk with you about them.
q2. can genetic testing results be used against me?
In the U.S., the Genetic Information Nondiscrimination Act (2008)
prohibits discrimination by health insurance companies and employers
based on genetic information. Depending on where you live in the
world, you may have different (or fewer) laws in this area.
q3. how should i tell my relatives about my genetic test
results?
There are many ways to share genetic test results. You and your family
may choose to share them by phone call, visiting in person, letter, or
email. It can sometimes be tricky because genetic testing is a very
personal process, and everyone reacts to this type of news differently.
Your doctor or genetic counselor can help you come up with a plan to
tell your family members, in a way that works best for all of you.
Test Result and Recommendations
To be completed by you and your doctor or genetic counselor, when
you receive your genetic test results and medical management
recommendations
test result
Negative: No mutations found
Positive: Mutation(s)
and
found in the
Carrier: Mutation
found in the Inconclusive: Variant(s) of unknown significance
found in the gene
gene
gene
recommendations for you
recommendations for family members
Genetic testing recommended for family members to consider
Genetic testing is not available or not something for family members to
consider at this time
Billing Questions: Ambry’s Patient Protection Plan
q1. what is ambry’s billing policy?
Ambry’s billing policy is to preverify insurance coverage (with or
without your sample) for genetic testing. We will contact you after your
sample is received, if your out-of-pocket cost is estimated to exceed
$100. We are committed to working with you and your clinician to
make the genetic testing process as simple and cost-effective as
possible, and our Billing Department is available to answer any
questions you may have. Our Billing Department can be reached by
phone at +1-949-900-5795 or billing@ambrygen.com.
q2. what is an explanation of benefits (eob)?
Your insurance company sends you an EOB to explain any treatments/
services paid on your behalf. It is not a bill and does not require
payment. You can contact us directly to speak with a Billing specialist
with any questions/concerns about your EOB.
q3. how much do ambry’s tests cost?
We are committed to making the genetic testing process as simple and
cost-effective as possible. Prices depend on if your insurance plan is
contracted with Ambry, and if they are a private or public plan. We also
offer prices when someone pays by cash, or when an institution pays.
This is not necessarily what is reflected on an EOB, so please contact
us directly to speak with a Billing specialist with any questions/
concerns.
q4. why did i receive a bill more than a month after my test?
Some genetic tests take weeks to process to receive the best results. In
addition, insurance companies can take over two months to process
claims, and longer if we need to send information again. All of this
could delay your bill, but we try our best to prevent this from
happening.
Resources
These and other resources can help build a sense of community and
help answer some common questions.
ambry’s general genetics site for families
patients.ambrygen.com/general-genetics
pcd foundation
pcdfoundation.org
genetic information nondiscrimination act (gina)
ginahelp.org
Find a Genetic Counselor
national society of genetic counselors
nsgc.org
canadian association of genetic counsellors
cagc-accg.ca
About Ambry
Ambry is a genetics-based healthcare company that is dedicated to
open scientific exchange so we can work together to understand and
treat all human disease faster.
ambry genetics
15 Argonaut
Aliso Viejo, CA 92656 USA
+1 866-262-7943
info@ambrygen.com
For more details about these tests, visit ambrygen.com
ambrygen.com
15 Argonaut, Aliso Viejo, CA 92656 USA
Toll Free +1 866 262 7943
Fax +1 949 900 5501
50339.3328_v4
PCDPGUI