What is Bloom syndrome?

Bloom syndrome (BS) is a genetic condition that has the following features:
• Small size (both before birth and after) – more in Chapters II and III
• (Often) A skin rash that develops in the sun – more in Chapter IV
• Immunodeficiency, meaning that the immune system does not function
properly, potentially leading to more infections or illnesses – more in Chapter V
• A greater risk of developing diabetes or other related endocrine issues – more
in Chapter VII
• A greatly increased risk of cancer – more in Chapter X
All that sounds really scary, but you should also realize that persons with Bloom
syndrome, while living with a chronic condition, are for the most part happy, healthy
individuals who live productive lives. The authors of this handbook are probably not
so different from you, and certainly do not spend all their time worried about this
diagnosis and its consequences. Healthy people with Bloom syndrome are healthy!

How is Bloom syndrome caused?

Bloom syndrome is a recessive genetic condition, which means that every person with
Bloom syndrome has two non-functioning copies of their Bloom gene (BLM).
Genes are passed down from parent to child. In the vast majority of cases, a person
with Bloom syndrome inherited one mutated gene from their mother and one
mutated gene from their father, who were both “carriers” of Bloom syndrome. (In
other, much more rare cases, a mutation may have arisen spontaneously very early on
in utero.) Carriers do not show any obvious signs of Bloom syndrome (more on that
in Chapter XII), so they often do not know they are carriers until after having had a
child who is diagnosed with Bloom syndrome.
If you and/or your child have had your BLM gene sequenced, please share that
information with the Bloom Syndrome Registry (see Appendix A). The Registry can
tell you whether it is a known mutation or whether you’re the first known person to
have it!

How is Bloom syndrome diagnosed?

Bloom syndrome is diagnosed either clinically (through observable features) or
through laboratory testing. Historically, diagnoses were made through clinical
observations of short stature, potentially a facial rash, and/or other features consistent
with Bloom syndrome. These days, the diagnosis is typically first suspected through
clinical observation and fully confirmed through genetic testing.

I’ve heard 23andMe tests for Bloom syndrome.
Can I or my child
be tested to confirm our diagnosis of Bloom syndrome?

23andMe is a direct-to-consumer genetic testing company that does offer a Food and
Drug Administration (FDA)-approved test for Bloom syndrome. However, this test
will ONLY detect the known mutation that is common in Ashkenazi Jewish
population, sometimes referred to as BLMAsh. If your mutation is one of the many
others that can cause Bloom syndrome, the 23andMe test will not reveal your
mutation. If you suspect your child has Bloom syndrome, or if you are curious about
which mutation(s) have caused your or your child’s Bloom syndrome, talk with your
doctor about ordering a more comprehensive genetic test that will test for all known
mutations that cause Bloom syndrome.

Who discovered Bloom syndrome?

Bloom syndrome was discovered by Dr. David Bloom in New York City in 1954,
where he noticed 3 children who were short and had rashes on their faces. He
suggested that this was a genetic syndrome, which was later confirmed through the
mapping of the BLM gene in the 1990s.

How many people have Bloom syndrome?

The Bloom’s Syndrome Registry has documented 287 cases of Bloom syndrome.
There are likely others with Bloom syndrome, as not all cases have been reported to
the Registry, and it may be that the condition is underdiagnosed in many countries.
With genetic sequencing becoming more common, and the internet allowing people
from across the world to connect more easily, it is likely that more cases will be seen
in the coming years.

What is the prognosis of Bloom Syndrome?

One of the first (and probably very scary) things that people faced with a new
diagnosis find online is that the median life span of persons with Bloom syndrome is
27 years old.2 This does not mean that the life expectancy of a child who was just diagnosed with
BS is 27 years! This number is a figure that is based on all of the records in the
registry, going back to the 1960s, and our understanding on how to screen for and
treat cancers has advanced immensely over the past half century! According to the
Registry, at least one individual lived to be 60 years old, which appears to be an
outlier. Nevertheless, some other persons with Bloom Syndrome have lived to be 50,
and more and more are living into their 40s.
That said, there are many complications that can be caused by Bloom syndrome,
affecting many different systems of the body. Make sure your doctor understands
Bloom syndrome and if he or she doesn’t, share this document with them and refer
them to the resources listed. Your health may depend on it!

What organizations exist to support persons and families with
Bloom Syndrome?

There are several groups and organizations that focus on research, support, and
community for persons with Bloom syndrome and their families.
• The Bloom Syndrome Registry (“BSR”):
o The BSR is the home for information on persons with Bloom syndrome.
Their work helps drive research on Bloom syndrome, and it is critical
that we help the Registry by providing information (given that Bloom
syndrome is such a rare condition, every case matters!).
o See: http://weill.cornell.edu/bsr/
o You may contact Dr. Chris Cunniff, the current head of the BSR at:
cmc9039@med.cornell.edu.
o See more about the BSR in Appendix A.
• Bloom’s Syndrome Association (“BSA”):
o The BSA is an international family support and patient advocacy
organization for persons affected by Bloom syndrome. The mission of
the BSA is “to foster interactions among its members, so that they might
learn from and support one another; to raise funds for research to
advance treatments and a cure for Bloom’s syndrome; and to raise public
2 See, for example: http://www.bloomssyndromeassociation.org/page/aboutbloomssyndrome
awareness about the syndrome and its importance to worldwide cancer
research.”
o See: http://www.bloomssyndromeassociation.org/
• Bloom’s Syndrome Foundation, USA (“BSF-USA”):
o The BSF-USA was founded in 2004 to “fund research aiming at the
development of a therapy for Bloom’s Syndrome and the prevention of
its complications, primarily the significant risk of developing cancers at
early ages.”
o See: http://www.bloomssyndrome.org/
• Bloom Syndrome Foundation, Europe (“BSF-Europe”):
o The BSF-Europe also funds research on BS, primarily in Europe.
o See: http://www.bloomsyndrome.eu/
• Bloom’s Connect:
o Largely operated through Facebook, Bloom’s Connect is a place for
persons with Bloom syndrome and their families to connect with one
another.
o See: https://www.facebook.com/groups/130771598288/
o An older site has additional information:
https://sites.google.com/a/bloomsconnect.org/www/
• Bloom Syndrome Nanocourse 2017 Facebook Page:
o This page grew out of the 2017 Nanocourse held at the CC-TDI and is
intended to be a place where Registry news and other updates can be
shared.
o See: https://www.facebook.com/groups/468812696835205/

There are two recent scientific publications on Bloom Syndrome that are
extremely useful to read and share with your doctor(s). We heavily reference
these papers in this handbook — we do not seek to reiterate what they share, but
have instead tried to summarize key points in easy-to-understand language, as
well as supplement with experiences from BS persons and families.
Bloom’s Syndrome: Clinical Spectrum, Molecular Pathogenesis, and
Cancer Predisposition by Christopher Cunniff, Jennifer A. Bassetti, and
Nathan A. Ellis. Molecular Syndromology 2017
Health Supervision for People with Bloom Syndrome* by Christopher
Cunniff et al.
* available on the Bloom Syndrome Association website via member access.

What other organizations and resources exist?

A broader list of organizations, websites, and resources are listed in Appendix B.
Read More:
• Help Me Understand Genetics: https://ghr.nlm.nih.gov/primer
• Scientific Overview of Bloom Syndrome, from GeneReviews:
https://www.ncbi.nlm.nih.gov/books/NBK1398/
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input!

How is growth affected in Bloom Syndrome?

Small size is one of the hallmark characteristics of Bloom syndrome. This growth
restriction starts before birth and adults with Bloom syndrome are frequently less than
5 feet (1.5 m) tall. Growth curves have not been systematically studied or updated in
the Bloom Syndrome Registry since 1999, but according to the data there, typically
men with Bloom syndrome grow to a final height of 1.49 m (4 ft, 10 in) and women
grow to 1.38 m (4 ft, 6 in).
These days, the amount of monitoring available for pregnant mothers and infants
means that small stature is often how Bloom syndrome is first suspected in an
individual. Terms such as “IUGR” (intrauterine growth restriction) and “failure to
thrive” are often familiar to parents of children with Bloom syndrome, both during
pregnancy and after. These can be very scary sounding terms to hear, but for people
with Bloom syndrome, once the syndrome has been recognized and diagnosed, many
other concerns that you and your doctor may have had about growth can be ruled
out.

Why are persons with Bloom Syndrome small?

At a most fundamental level, scientists still don’t know what causes persons with
Bloom syndrome to be below “normal” size. They hypothesize that it may be due to
either one or more of the following:
• Slower cell proliferation, due to the fact that it takes longer for DNA
replication to happen in cells lacking the BLM protein.
• Endocrine issues, as the endocrine system does seem affected in other ways
(see Chapter VII).
• More cell death due to mutations caused by the lack of the BLM protein.
Further research is needed to uncover the reason(s) for small size. This is an example
of why it is important to keep your records up to date in the Bloom Syndrome
Registry – this is one of the ways that we can stimulate research!

How does my child’s height/weight/etc. compare to others with
Bloom Syndrome?

Before diagnosis, many parents of infants and toddlers may be concerned that they
are not feeding their child enough or that reflux or other conditions are causing their
child to be malnourished. Even after diagnosis, many people (including doctors!) still
struggle to know how small is “too” small.
An analysis of the data in the Bloom Syndrome registry from the 1990s (Keller 1999)
found that growth rates for persons with Bloom syndrome are different than those of
the general population. The authors of this handbook have used the data to produce
growth charts for people with Bloom syndrome, which can be found in Appendix C
of this Handbook. Our hope is that these can be used by yourself and your doctors to
get a sense as to how your or your child’s growth compares to others with Bloom
syndrome.C
Parents of children with Bloom syndrome share stories with one
another about trying to estimate the number of calories lost to a
puddle of baby vomit on the floor. Many of the authors of this
Handbook have been there, and we are here to tell you that your child’s
slow growth is almost certainly not caused by your inability to feed them — it is
caused by Bloom syndrome. Stressing out about that puddle isn’t going to
help anything. The best thing you can do for your child is to make
sure you and your child’s doctors are as well informed as possible
about Bloom syndrome and how to care for children with this
complication.

Will putting my child on a feeding tube increase their growth?

The Registry has reported that Bloom syndrome children who were given
supplemental feeding (through an NG- or G-tube) did see results in increased fat, but
not height. Anecdotally, some families who did put their child on feeding tubes have
said that it did not increase intake, as the child refused to take food orally and/or had
increased vomiting.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input!
C Contact the editor if you’d like to get a copy of the growth charts as an Excel spreadsheet.

How do I know whether my child is properly nourished when
s/he seems so small?

As discussed in Chapter II, it can be challenging to know what is typical for a child
with Bloom syndrome, and the lack of (or low level of) fat in children with Bloom
syndrome can make them appear to be undernourished. Young individuals with
Bloom syndrome typically have very little subcutaneous fat, which contributes to the
malnourished look. It can be helpful to work with a nutritionist, especially one trained
to work with children or adults with genetic disorders that may have needs that differ
from someone who may be just a “picky eater.” As a start, tracking your child’s
growth on the growth charts in Appendix C should give you a sense as to whether
your child is following his or her own growth curve.
Aside from that, while it may be tempting to feed your child high calorie, low
nutritional value foods, it’s important to remember that diabetes can be common in
Bloom syndrome and it’s likely better to offer a wide range of healthy options and to
let your child grow at their own pace. It could be more important for your child to
develop a healthy relationship with food than to force extra calories in the hopes of
having them gain a few ounces.

I am/my child is anemic – is that normal in Bloom syndrome?

Several persons with Bloom syndrome have reported being anemic. To the best of
our knowledge, it is not something that the Registry or other researchers have studied
to understand the prevalence or underlying cause. It is worth having bloodwork done
to check for anemia or other deficiencies, and taking appropriate vitamins to
supplement any deficiencies.

My baby/child with Bloom Syndrome has severe reflux and vomits
after bottles/meals. What should I do?

Reflux (often referred to as Gastroesophageal reflux disease or GERD) is one of the
more common symptoms of Bloom syndrome in infants and young children. Consult
with a GI specialist, and they may recommend medications. However, many families
have noted that the common medications do not help, or help only mildly. Small,
frequent meals seem to be better than larger feeds, and having your baby or child
sleep on a small incline may help.
Most children grow out of the reflux by age 2-3, but some of the GI issues such as
nausea or a feeling of fullness persist even into adulthood.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here? Contact the editor – we’d love to have your input!

What do we know about the facial rash commonly seen in persons
with Bloom Syndrome?

One of the first features noticed by Dr. Bloom that led to his concluding that Bloom
syndrome was in fact a syndrome was a facial rash, in a “butterfly” shape across the
nose and cheeks. This rash appears to be due to a reaction of the skin to ultraviolet
radiation (UV rays) – mostly commonly from the sun, but also from halogen lamps or
lightbulbs.
While described as a facial rash, this rash can also appear on the neck, shoulders,
hands, chin, and may cause a blistering of lips. It is not always in a “butterfly” pattern,
either.
It is not known exactly what causes this rash, nor why it only appears where it does
and not on other parts of the body. Some have said the rash seems to be made worse
by heat, but the cause of this relationship has not been established.

Does everyone with Bloom Syndrome have the facial rash?

It does not seem that everyone with Bloom syndrome has experienced the rash. This
is true anecdotally and also has been reported in the literature (see Appendix D:
References). It is not known whether there is any underlying relationship between
which specific genetic mutation(s) led to Bloom syndrome and the presence or
absence of a facial rash.

Do persons with Bloom Syndrome “grow out” of the rash?

It is reported that the facial rash is more common in children under the age of 3, but
others have reported that their rash did not first appear until a later age. Most parents
of children with Bloom syndrome become vigilant with sunscreen and children get
better at applying and re-applying sunscreen and wearing hats as they get older, so it is
challenging to know whether the rash gets better over time or is just less likely to
appear due to sun protection. That said, most persons say that it does get less
frequent and severe with age.

Is there a treatment for the facial rash?

According to most, the rash or blisters are not painful, but may be itchy, and do not
necessarily need to be treated unless it becomes infected. For a severe rash, some
dermatologists have prescribed a cortisone cream or recommended over-the-counter
zinc oxide, but most persons report these are not effective. Some dermatologists may
prescribe steroid cream, but long-term use of steroids can have complications, in that
they weaken the immune system.
If the rash becomes infected, it should be seen by a doctor who may prescribe
antibiotics.

How can I avoid the facial rash?

Always use a high sun protection factor (SPF) sunscreen on exposed body parts,
including face and hands. Wearing a hat or baseball cap can also minimize direct sun
exposure. Try to avoid direct sun exposure during high UV hours (i.e. 10am – 2pm).
If you have a child in school, work with your school system to make sure that
sunscreen is being reapplied to your child once or twice during the day.

Are there other skin issues associated with Bloom syndrome?

Birthmarks known as “café-au-lait” spots are common in persons with Bloom
syndrome, as are some areas that are darker or lighter than the surrounding skin.
These are not known to cause any problems by themselves, but may be a cosmetic
issue for some.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input!

How is the immune system affected in Bloom syndrome?

It is common in persons with Bloom syndrome to have a slight or moderate
immunodeficiency, even if they show no other signs of being sick.
Children with Bloom syndrome in particular are reported to get frequent ear
infections, stomach upsets, colds and/or lung infections, especially in their younger
years. Some children with Bloom syndrome do not get sick any more frequently than
other children. If you think your child may have an infection, it is important to
consult with your pediatrician to properly diagnose and treat. If you are unsure if your
child needs to be seen, call your doctor’s office and let them guide you until you get a
feel for your child’s regular “patterns.”
At a fundamental level, scientists still do not understand how exactly the BLM protein
affects the immune system. It is hypothesized that perhaps: (1) lymphocytes (white
blood cells that are part of the immune system) do not proliferate as well in persons
with Bloom syndrome; and/or (2) there’s a defect in something called “class
switching” as immune cells try to change between one type and another.

How do I know if my or my child’s immune numbers are low?

Current guidelines (see the Health Supervision paper) recommend only testing
immunoglobulin (antibody) levels if there is a sign of immunodeficiency. That said,
there may be value in knowing your or your child’s immunoglobulin levels to have a
baseline in case anything develops in the future.
A lab test for immunoglobulins will report on the three major immunoglobulins: IgG,
IgA, and IgM. Most commonly reported in Bloom syndrome is that IgG is low
normal, and especially IgG2 is low.

What can I do if my or my child’s immune levels are low?

Even if your child seems perfectly healthy, persons with Bloom syndrome often show
low immunities. This can mean that an infection can progress quickly.
If IgG/IgM levels are very low, your doctor may recommend IVIG therapy as your
child gets older. Some persons report that IVIG is very helpful in making them feel
better and fight off infections, while others have had mildly negative responses to the
IVIG infusion itself. Taking an anti-histamine before the IVIG infusion has helped
some with the irritation caused by the infusion.

What should I do about childhood vaccines?

Given that your child may be immune-deficient, keeping them on the prescribed
schedule for childhood vaccines is critically important. It is important to note that
some have reported that certain childhood immunizations were not successful in
producing antibodies – i.e. they didn’t work. Your child’s doctor should be made
aware of this and may want to test your child’s antibody response to vaccinations and,
if they do not show the normal response, may recommend receiving a “booster”
vaccine.
You may also want to keep your child away from children who have not been
immunized. Although we are not aware of documented cases of a child with Bloom
syndrome getting measles or mumps, it could be a concern as fewer people get
vaccinations. Whooping cough is on the rise in the United States, and could be a
particular concern given that people with Bloom syndrome are at increased risk for
lung infections.

I keep hearing about harnessing the immune system to fight cancer
– is that something I or my child would be eligible to use if/when
cancer strikes?

Immuno-oncology is one of the hottest areas of research in the cancer world today
and is increasingly being used as a frontline in certain types of cancers. At present, not
enough is known about the immune system in Bloom syndrome to know whether
current emerging therapies (checkpoint inhibitors and CAR-T, among others) would
be effective in treating Bloom syndrome cancers, as the immune system is affected in
Bloom syndrome in a way that is not completely understood. That said, there is much
hope for these therapies given they are much less toxic than chemotherapy or
radiation.
Ask your oncologist about these therapies and, if you do end up prescribed one of
them, talk with the Bloom Syndrome Registry so that others can learn from your
experience!
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input!

Are persons with Bloom syndrome more susceptible to dental
problems?

There are some reports of low or no natural enamel coating on some of the teeth,
making them prone to cavities. There has also been reports of weakened teeth that
may chip or crack easily.
It’s not known what causes the above, and whether there may be a connection to the
reflux commonly seen in younger years, or whether it is a part of the syndrome that is
not fully understood.

What can I do to protect my or my child’s teeth and mouth?

Early and regular dental exams are key. It is also important that your dentist
understands that people with Bloom syndrome are far more susceptible to cancer
than the general population.
Strive for regular dental check-ups and cleanings every 6 months, as called for in the
Bloom Syndrome Health Supervision paper. You may also want to discuss with your
dentist about having sealants placed on your child’s primary and/or secondary teeth.
There have been reported cases of oral cancer with Bloom Syndrome. Typically,
dentists do head and neck exams and oral cancer screenings on adult patients.

What should I do if my dentist wants to do x-rays of my or my
child’s teeth?

First and foremost, make sure your dentist understands Bloom syndrome and the
possible risks associated with radiation. (If you don’t think he or she understands, do
not hesitate to change dentists!)
Most dentists follow the ALARA (As Low as Reasonably Achievable) principle of
radiation exposure. This means a dentist will take as few x-rays as possible in order to
evaluate a patient and make a diagnosis. As Bloom patients typically have smaller
mouths than the general population, it is reasonable to expect that less x-rays will be
taken than an average patient. (2 bitewing radiographs for a Bloom patient vs 4 for a
typical patient, for example).

As the thyroid is the most susceptible area of the head and neck region to absorb
radiation, the neck region should be shielded with a lead apron for any x-ray
exposures.
X-rays have been used by persons with Bloom Syndrome for dental care. Some have
had braces, and others have needed x-rays for other purposes.
CBCT (Cone Beam Computed Tomography) scanners are a new technology being
utilized more in dentistry. The routine use of a CBCT scan for evaluation is
controversial due to its higher level of ionizing radiation. Using a CBCT scan for
routine evaluation for a Bloom patient should be avoided. If a CBCT needs to be
done for a specific reason or diagnosis (ie: the surgical placement of an implant), the
dentist should use the smallest field size possible. In addition, some newer CBCT
models have an ultra-low radiation dose mode. (Planmeca scanners utilize this
technology). This mode should be utilized for Bloom patients whenever possible.
You may wish to discuss with your dentist whether any alternative diagnostics are
available.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input!

Are persons with Bloom syndrome predisposed to diabetes?

Diabetes does appear more frequently in the Bloom syndrome community than in the
general population, and it develops at an earlier age than in the general population. It
has been diagnosed in children as young as age 4, but on average appears around age

How should I be monitored for endocrine issues?

The Bloom Syndrome Health Supervision Guidelines recommends that fasting blood
sugar measurements and lipid profiles begin annually at age 10. Talk to your doctor
about seeing an endocrinologist earlier if your child has any symptoms before age 10.
If you have any symptoms of hypothyroidism, such as fatigue, constipation, cold
sensitivity and weight gain, talk to your doctor about testing your thyroid function.

My doctor has told me I’m “pre-diabetic.” What does that mean?

Pre-diabetes can be considered a “warning sign” – it’s when your blood glucose level
is higher than the healthy range, but is not high enough to be considered diabetic.
Talk with your doctor about what he or she recommends.

What do we know about growth hormone therapy in persons with
Bloom syndrome?

There have only been a few reported cases of growth hormone therapy used for
persons with Bloom syndrome. In cases published in the literature (Reyes 2013, Brock
1991, and Stahnke 1992), four out of five children developed cancer, most commonly
B-cell Non-Hodgkin’s Lymphoma. What we don’t know is whether these cancers
were related to the growth hormone treatment or whether they would have developed
otherwise.
There are other, unpublished, reports of Bloom syndrome children having been on
growth hormone therapy with seemingly no cancers developing as a result. These
children anecdotally did show increased growth as a result of GH treatment.
According to the Gene Reviews entry authored by the Registry (link below), growth
hormone administration to children with Bloom syndrome has not led to increased
growth rate or adult height in most persons, but some have experienced improved
linear growth. Use of growth hormone has been approached cautiously in this
population, because of the theoretic increase in their risk to develop tumors as a result
of their treatment.
The Bloom Syndrome Health Supervision paper recommends that great caution
should be used if growth hormone is prescribed and that monitoring for cancers will
be of utmost importance. Specifically, the paper states that growth response, serum
IGF1, and IGFBP3 levels should be monitored during growth hormone therapy; and
therapy should be discontinued if there is no response.

What do we know about delaying puberty in persons with Bloom
syndrome?

Some families have hormonally delayed puberty in their children to allow the bones a
few more years to grow. This has, anecdotally, resulted in increased height compared
to what would have been expected from earlier growth charts.
It is also important to note that some groups feel that medically (hormonally)
intervening is considered unethical as it changes the natural course of growth.
These questions are undeniably complex and should be done in close consultation
with medical professionals (endocrinologist, oncologist, possibly psychologist and/or
psychiatrist), but ultimately each person and family will have to carefully make their
own decision as to which course to take.
Read more:
• Bloom Syndrome Association’s page on the Digestive System (including
metabolism):
http://www.bloomssyndromeassociation.org/?page=thedigestivesystem
• GeneReviews article on Bloom’s syndrome:
https://www.ncbi.nlm.nih.gov/books/NBK1398/
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input!

Can persons with Bloom Syndrome have children?

Women with Bloom Syndrome have had children, but do experience difficulty in
getting pregnant and many go through menopause much earlier than the general
population.
It is less clear how many men with Bloom syndrome are fertile. Not many have been
studied, but, of those that have, most have been azospermic (meaning they do not
have viable sperm in the semen), while one was severely oligospermic (meaning a low
sperm count). Interestingly, a recent paper of a case in Tunisia seemed to show that a
man with Bloom syndrome had successfully fathered a child (see Appendix D:
References). Clearly more research is needed in this area.

Who should I talk with about fertility issues?

Talk with your general practitioner about getting a referral to a fertility specialist.
Make sure to share information about Bloom syndrome with him/her, and discuss
your options. While the road may be challenging, it may not be impossible.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
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Are persons with Bloom syndrome at risk of having intellectual
disabilities or learning difficulties?

This is not a well-documented area for Bloom syndrome. Anecdotally, there have
been reports of learning disabilities and/or Attention Deficit Hyperactivity Disorder
(ADHD) being more common in the Bloom syndrome-affected children than those
not affected. That said, it is known that ADHD and related conditions are more
common in children born premature, so untangling the ultimate cause or true relation
to Bloom syndrome is difficult. The Registry has reported in the past that participants
were of normal intelligence, with some participants having achieved higher levels of
education.
Anecdotally, some persons with Bloom syndrome and their families say they have
experienced learning difficulties and differences including dyslexia. If this is the case
for you or your child, talk with your local school district. In the United States, by law,
they are required to assess your child if you request an evaluation and, if found eligible
for services, they will work with you to come up with an Individualized Education
Plan (IEP).

Read more:

• U.S. Department of Education Guide to the Individualized Education
Program: https://www2.ed.gov/parents/needs/speced/iepguide/index.html
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
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Why do persons with Bloom syndrome have a higher risk of
cancer?

Cancer arises when cells begin to divide without stopping and spread into surrounding
tissues. Cancer is caused by mutations in genes that control the ways our cells grow
and divide. Each time a cell divides, it must copy over its DNA; this process is errorprone, leading to mutations. Mutations also accumulate in response to external
exposures such as tobacco smoke and radiation (see Chapter XV for more on
Environmental Exposures). The BLM protein helps to fix those errors, so persons
with Bloom syndrome, lacking the BLM protein, are more likely to have mutations
that were unable to be fixed, and thus are more likely to develop cancers.

What is the risk of developing cancer?

According to the Registry, at least 33.4% of individuals with Bloom syndrome
develop cancer by age 25, and at least almost 80.9% of individuals with Bloom
syndrome develop cancer by age 40.
As of 2018, the Registry is currently performing a more thorough analysis to
understand the frequency of cancer by type of cancer. In the meantime, a table
describing the cancers reported to the Registry can be found in the Health
Supervision Guidelines paper.

Does Bloom syndrome make cancer more likely / faster to spread?

This is currently unknown and more research is needed. In any case, for most cancers,
earlier detection and treatment leads to better outcomes. Following the recommended
health supervision guidelines, and talking with your doctor as soon as possible if
something seems “off”, is advised.

Whom should I contact (and have my doctors contact) if cancer is
diagnosed? Who are the world’s experts on treating cancer in
persons with Bloom syndrome?

The Registry can put your oncologist in touch with other oncologists who have
treated cancer in persons with Bloom syndrome. Certain oncologists have treated
multiple cancers in multiple persons with Bloom syndrome.
As a community, it is important that we share information on our cancers and
protocols used to treat them. Please share with the Registry, which can serve as a
clearinghouse for this information, and help others!

What types of cancer have persons with Bloom syndrome had?

Persons with Bloom syndrome may develop many different cancer types. Leukemia
(particularly Acute Myeloid Leukemia) and lymphoma (particularly non-Hodgkin) are
the most common cancer types. Colorectal cancer, breast cancer, skin cancer, and
Wilms tumor, are also more common than in the general population.

How should I be monitored for cancer?

The Health Supervision Guidelines paper recommends the following surveillance
schedule:
Clinical Condition Screening/Prevention Recommendations
Leukemia • Awareness of symptoms of leukemia, such as pallor, abnormal bleeding,
petechiae, fatigue, and unintentional weight loss
Lymphoma • Awareness of symptoms, such as enlarged lymph nodes, unexplained
fevers, night sweats, fatigue, unintentional weight loss
• Whole body MRI scanning every 1-2 years, starting at age 12-13
Colorectal Cancer • Annual colonoscopy and fecal immunochemical testing every 6 months,
starting at age 10-12 years
Breast Cancer • Annual breast MRI scans, starting at age 18
Skin Cancer • Reduce excessive exposure to sunlight
• Cover exposed skin
• Use a broad spectrum sunscreen with SPF of 30 with application twice
daily and every 2-3 hours if outdoors
Wilms Tumor • Awareness of symptoms, such as hematuria and a painless abdominal
mass
• Abdominal ultrasound every 3 months, starting at diagnosis to age 8

If I develop cancer, does it need to be treated differently?

YES! It is important that your oncologist understand Bloom syndrome and that you
are at an increased risk for secondary cancers if treated with chemotherapy and/or
radiation.
Chemotherapy regimens should be adapted; patients have typically tolerated 50% or
below the normal regimen dosage. Ionizing radiation or alkylating agents are not
recommended, due to their risk of potential additional damage.
We hope to compile more cancer protocols that have been used in the past. In the
meantime, contact the Registry if you are diagnosed and you can be put in touch with
others who have successfully beat cancer to learn more about their experiences.

Read more:

• National Cancer Institute’s “What is Cancer?”: https://www.cancer.gov/aboutcancer/understanding/what-is-cancer
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input

What pulmonary issues are associated with Bloom syndrome?

Several individuals in the BSR died due to Chronic Obstructive Pulmonary Disease
(COPD), and others have had recurrent bronchitis. If bronchitis is common, consult
with your immunologist about testing for an immunodeficiency.

What can I use to help with my bronchiectasis?

The Health Supervision Guidelines paper recommends cough assist devices, vibration
vests, and daily nasal lavage may be helpful in clearing mucus out of the chest and
sinuses.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input

What eye/vision issues are associated with Bloom syndrome?

None have been documented in the literature, but some have anecdotally said they’ve
had issues including astigmatism (some have had while younger and have grown out
of it) or poor vision in general. If you have experience with this, contact the editor!
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input

Does Bloom syndrome affect hearing?

Several persons with Bloom syndrome have reported hearing difficulties, some of
which were present from birth, or developed a young age (perhaps due to multiple ear
infections, caused by reflux) and others that developed over time with the use of
antibiotics that have hearing loss as a side effect. There’s no evidence (to the best of
our knowledge) that Bloom syndrome in and of itself causes hearing difficulties,
although at least one individual has reported having moderate hearing loss from birth.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input

At what age should I tell my child he/she has Bloom syndrome?

This is a difficult question with no single right answer. Families with children with
other genetic conditions face the same question. Some useful points from a page on
Autism Spectrum Disorder:3
“A child’s personality, abilities and social awareness are all factors to consider
in determining when a child is ready for information about their diagnosis.”
“Many families have found that setting a positive tone about each family
member’s uniqueness is a wonderful starting place. A positive attitude about
differences can be established if you start as early as possible, and before the
diagnosis is mentioned. Everyone is in fact unique with their own likes and
dislikes, strengths and weaknesses, and physical characteristics. Differences are
discussed in a matter of fact manner as soon as the child or others their age
understand simple concrete examples of differences. With this approach, it is
more likely that differences, whatever they are, can be a neutral or even fun
concept. Matter of fact statements such as “Mommy has glasses and Daddy
does not have glasses” or “Bobby likes to play ball and you like to read books”
are examples. The ongoing use of positive concrete examples of contrasts
among familiar people can make it easier to talk about other differences related
to your child’s diagnosis with him or her.”
Talk with your child’s pediatrician about what concepts might be age-appropriate to
share.

How can I connect with others with Bloom syndrome?

The Bloom’s Connect Facebook page, the Bloom’s Syndrome Association membersonly site, and conferences are great places to meet others with Bloom syndrome.
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input
3 https://www.iidc.indiana.edu/pages/Getting-Started-Introducing-Your-Child-to-His-or-HerDiagnosis-of-Autism-or-Asperger-Syndrome

What environmental factors may impact Bloom syndrome?

As described above, persons with Bloom syndrome should avoid direct sun exposure
because of increased risk of both cancer and facial rash. In addition to UV exposure,
persons with Bloom syndrome should avoid or limit exposure to known or likely
carcinogens, mutagens, and reprotoxins (CMRs).
• Carcinogens (C): substances and preparations which, if they are inhaled or
ingested or if they penetrate the skin, may induce cancer or increase its
incidence.
• Mutagens (M): substances and preparations which, if they are inhaled or
ingested or if they penetrate the skin, may induce heritable genetic defects or
increase their incidence.
• Reprotoxins (R): substances and preparations which, if they are inhaled or
ingested or if they penetrate the skin, may produce or increase the incidence of
non-heritable adverse effects in the progeny and/or an impairment of male or
female reproductive functions or capacity.
More information on this topic is available via the resources listed below.

Read more:

• Cancer-Causing Substances in the Environment. National Cancer Institute
• Risk Factors for Cancer. National Cancer Institute
• Known and Probable Human Carcinogens. American Cancer Society
• 10 Household Tips for Cancer Prevention. Environmental Working Group
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input

What should I know about being a carrier of Bloom syndrome?

If you are a carrier of Bloom syndrome, you have only one functioning copy of the
BLM gene. If your partner also is a carrier of Bloom syndrome, it means any offspring
have a 25% chance of having Bloom syndrome, a 50% chance of being a carrier, and
a 25% chance of having two functioning copies of BLM and not being a carrier.
Depending on how your child was diagnosed with Bloom syndrome, you may have
had your BLM gene sequenced and know your mutation. It may be a mutation already
known to the BSR, or a completely novel (new) mutation. Either way, please share
this information with the BSR so that more can be learned about Bloom syndrome.

Are carriers at an increased risk of cancer?

It’s currently unknown whether carriers are at an increased risk of developing cancers;
if they are, the risk is only slightly higher than the general population. In animal tests
used in research, carriers have been found to be at an increased risk. Population
studies of humans have found conflicting results. Nevertheless, you should discuss
with your doctor the fact that you are carrier of Bloom syndrome and discuss whether
he or she recommends any cancer surveillance differing from guidelines for the
general population.
More information on this topic is available via the resources listed below.

Read more:

• Inherited Variants in BLM and the Risk and Clinical Characteristics of Breast
Cancer. Cancers
Do you have a question you’d like to see answered, or do you have an experience that differs from what is listed here?
Contact the editor – we’d love to have your input

We hope that this document will grow over time to include other perspectives and,
that by posing questions, we may be able to drive research and inquiry into those areas
most pressing to affected individuals and their families. As stressed at the end of each
chapter, please do share your thoughts on your experiences, or suggest additional
questions you’d like to see answered!

Overview and History of Registry

The Bloom’s Syndrome Registry at the Weill Cornell School of Medicine was
established in 1960 to collect information on affected individuals and their families.
Dr. James German was head of the registry for many years and personally collected
information and biological samples from individuals with Bloom syndrome and their
families.
In 2012, Chris Cunniff became the new registrar. He has been working to update the
registry’s information and to move older, paper files into a digital repository.

Importance of keeping information up-to-date with Registry

Registries in rare diseases are incredibly important. Because of the difficulty in doing
clinical trials in populations with such few numbers, information in a registry can be
used as a “natural history” to which a potential treatment might be compared.
Sharing any updates to your health, or anything else that you or your child experience
with Bloom syndrome, is an important part of building that natural history for Bloom
syndrome. The Registry also hopes to build on the momentum of the past few years
to have more regular conferences and other activities and making sure your
information is up to date is the best way to be a part of that momentum!

Contact the Registry:

Chris Cunniff, MD
Chief, Division of Medical Genetics
646-962-2205
Mailing address:
Chris Cunniff, MD
Division of Medical Genetics
Weill Cornell Medicine
525 East 68th Street, Box 128
New York, NY 10021

Read More:

• The Bloom Syndrome Registry website: http://weill.cornell.edu/bsr/
• NIH information about patient registries: https://www.nih.gov/healthinformation/nih-clinical-research-trials-you/list-registries

Bloom Syndrome Organizations

• Bloom Syndrome Association: http://www.bloomssyndromeassociation.org/
• Bloom Syndrome Foundation (Europe): http://www.bloomsyndrome.eu/
• Bloom Syndrome Foundation (USA): http://www.bloomssyndrome.org/
• Bloom’s Connect Facebook page:
https://www.facebook.com/groups/130771598288/
• Bloom Syndrome Nanocourse 2017 Facebook page:
https://www.facebook.com/groups/468812696835205/

Cancer Research and Information

• American Association for Cancer Research (AACR): http://www.aacr.org
o AACR Recommendations for Childhood Cancer Screening and
Surveillance in DNA Repair Disorders (including Bloom syndrome):
http://clincancerres.aacrjournals.org/content/23/11/e23
• American Society for Clinical Oncology (ASCO): https://www.asco.org/
• National Institutes of Health: https://www.nih.gov/
o National Cancer Institute: https://www.cancer.gov/
• American Cancer Society: https://www.cancer.org/

Rare Diseases

• National Organization for Rare Disorders (NORD): https://rarediseases.org/
• Global Genes: https://globalgenes.org/

The growth charts here have curves for persons with Bloom Syndrome that are taken
from a paper published in 1999. These charts are designed to be printed out on a full
page so that you can take them to your doctors and chart progress on them by hand if
you wish.
The data used to make those curves were limited, so they should not be taken too
literally, particularly near their endpoints. Wes Campbell keeps these curves and
updates them, so feel free to contact him (wes@physics.ucla.edu) if you have any
questions or requests.
Note: we need additional information to make sure these growth charts are as accurate as can be!
Please provide your/your child’s charts to the Registry, if possible

Weight for Age 0-36 months, Females with Bloom Syndrome

Length for Age 0-36 months, Females with Bloom Syndrome

Weight for Length 0-36 months, Females with Bloom Syndrome

Weight for Age 2-18 yrs, Females with Bloom Syndrome

Height for Age 2-18 yrs, Females with Bloom Syndrome

Weight for Height 2-18 yrs, Females with Bloom Syndrome

Weight for Age 0-36 months, Males with Bloom Syndrome

Length for Age 0-36 months, Males with Bloom Syndrome

Weight for Length 0-36 months, Males with Bloom Syndrome

Weight for Age 2-18 yrs, Males with Bloom Syndrome

Height for Age 2-18 yrs, Males with Bloom Syndrome

Weight for Height 2-18 yrs, Males with Bloom Syndrome

To find any of the below references, you may copy and paste the Digital Object
Identifier (DOI) (the weird number following each reference’s title) into your internet
search engine or the search box at https://dx.doi.org/

Overview/Review Articles

• Bloom’s Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer
Predisposition (2016): 10.1159/000452082
• Health Supervision paper

Summaries of Bloom Syndrome Workshops/Events

• Bloom syndrome: research and data priorities for the development of precision
medicine as identified by some affected families (2018): 10.1101/mcs.a002816
• Bloom’s syndrome workshop focuses on the functional specificities of RecQ
helicases (2008): 10.1016/j.mad.2008.09.005

Growth

• Growth deficiency and malnutrition in Bloom syndrome (1999):
10.1016/S0022-3476(99)70206-4

Facial Rash/Dermatology

• First Two Cases of Bloom Syndrome in Russia: Lack of Skin Manifestations in
a BLM c.1642C>T (p.Q548X) Homozygote as a Likely Cause of
Underdiagnosis (2017): 10.1159/000454820

Immunology

• The Bloom’s Syndrome Helicase Is Critical for Development and Function of
the alpha-beta T-Cell Lineage (2007): 10.1128/MCB.01402-06
• Immunodeficiency in Bloom’s Syndrome (2018): 10.1007/s10875-017-0454-y

Cancer Screening

• Recommendations for Childhood Cancer Screening and Surveillance in DNA
Repair Disorders (2017): 10.1158/1078-0432.CCR-17-0465
• Health Supervision paper
48

Cancer Treatment

• Toxicity of Chemotherapy in a Patient with Bloom Syndrome’s Diagnosis
(2017): 10.17265/2328-2150/2017.07.006
o Unsuccessful treatment of 21 year old in Brazil
• Successful treatment of mature B-cell lymphoma with rituximab-based
chemotherapy in a patient with Bloom syndrome (2017): 10.1002/pbc.26385
o Successful treatment of 11 year old in Saudi Arabia
• Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome (2016):
10.1155/2016/3176842
o Successful treatment of 40 year old in Brazil
• Burkitt lymphoma in a child with Bloom syndrome: Burkitt’s lymphoma and
Bloom syndrome: about a pediatric observation (2016):
10.1016/j.arcped.2015.12.004
o Unsuccessful treatment of 5 year old in Tunisia
• Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in
girl with Bloom syndrome (2014): 10.4172/2157-7412.1000177
o Unsuccessful treatment of 9 year old in UK
• Proton beam therapy for malignancy in Bloom syndrome (2013):
o Unsuccessful treatment of 32 year old in Japan
• Discrepant outcomes in two Brazilian patients with Bloom syndrome and
Wilms’ tumor: two case reports (2013): 10.1186/1752-1947-7-284
o Successful treatment of 3.5 year old in Brazil; Unsuccessful treatment of
4 year old in Brazil
• Bloom syndrome complicated by colonic cancer in a young Tunisian woman
(2011): 10.1016/j.clinre.2011.06.001
o Unsuccessful treatment of 19 year old woman in Tunisia
• Combined modality treatment for locally advanced squamous-cell carcinoma of
the oropharynx in a woman with Bloom’s syndrome: A case report and review
of the literature (2001): 10.1023/A:1011106202939
o Unsuccessful treatment of patient in Australia

Cancer Risks for Carriers

• Deleterious Germline BLM Mutations and the Risk for Early onset Colorectal
Cancer (2015): 10.1038/srep14060