Waardenburg Syndrome

Chantal Joy Moshakos GN 301 002 November 18, 2007 “I have neither given nor received unauthorized aid on this assignment” _________________________

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PART A: Waardenburg syndrome is a rare genetic disorder which is often characterized by

hearing and pigmentation mutations. Waardenburg was named by Petrus Johannes

Waardenburg, a Dutch eye doctor, who was the first to see a link between hearing loss

and people with differently pigmented eyes (NIDCD, 2007). In 1951, Waardenburg

noted six major characteristics associated with the different types of Waardenburg

syndrome: high nasal root, medial eyebrow flare, partial or total pigmentation differences

of the iris’s, deaf-mutism from birth, and a white forelock (Tagra et. Al, 2006).

Waardenburg’s most commonly affects the pigmentation of the skin, hair, and

iris’s of the eyes. Those afflicted with Waardenburg’s often have very pale, vivid blue

eyes or different color eyes. One blue eye and one brow eye is the most common

occurrence although occasionally the iris will have two different colors in it such as half

blue and half brown. Waardenburg’s is also often characterized by a white forelock. The

white forelock is usually on the midline of the hair but can also be found farther back on

the midline. Although the forelock is usually white, there have been some cases of red or

black forelocks associated with Waardenburg syndrome (Milunsky, 2007). Another

characteristic of Waardenburg syndrome is premature graying. Premature graying is

graying before the age of thirty although it is often found at much younger ages in people

with Waardenburg syndrome. In rare cases, other more debilitating impairments are

associated with Waardenburg’s such as upper limb musculoskeletal deformities, joint

contractures, disorders affecting the spine, and cleft lip/palate (NIDCD, 2007).

Not everyone afflicted with Waardenburg’s has hearing loss. Hearing loss usually

only afflicts 60% of those diagnosed with the syndrome (USNLM, 2006). On the other

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hand, Waardenburg accounts for approximately 2-3% of the cases of patients with

congenital hearing loss (Ezzell, 1992).

There are four main types of Waardenburg syndrome denoted as types I-IV. The

most prevalent are types I and II. Some of the types of Waardenburg syndrome go by

different names. When a person mentions Waardenburg syndrome without a number

following it, they are traditionally talking about Waardenburg Syndrome type I.

Waardenburg syndrome type II is often called Waardenburg syndrome without dystopia

canthorum (the appearance of wide set eyes) (Polzin, 2002). Type III is usually referred

to as Klein-Waardenburg syndrome and is differentiated from the others because it is

usually characterized by upper limb deformities (Mckusick, 2006). The last type of

Waardenburg’s, type IV, is extremely rare and usually goes by the name of

Waardenburg-Shah or Waardenburg-Hirschsprung because it is associated with

Hirschsprung’s disease which affects the intestines by causing blockages and constipation

(USNLM, 2006).

The Waardenburg Consortium has devised a set of diagnostic criteria used to

diagnose patients with Waardenburg type I. For a patient to be diagnosed with type I,

they must have two major criteria or one major and two minor criteria. The criterion

includes:

Major Criteria

• Congenital sensorineural hearing loss • White forelock, hair hypopigmentation • Pigmentation abnormality of the iris

o Complete heterochromia iridum (irides of different color) o Partial/segmental heterochromia (two different colors in same iris,

typically brown and blue) o Hypoplastic blue irides, or brilliant blue irides

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• Dystopia canthorum, W index >1.95 * • Affected first-degree relative

Minor Criteria

• Skin hypopigmentation (congenital leukoderma) • Synophyrys/medial eyebrow flare • Broad/high nasal root, prominent columella • Hypoplastic alae nasi • Premature gray hair (before age 30 years)

(Milunsky, 2007)

If a patient fits the required criteria above, they are diagnosed with Waardenburg

type I.

Another way doctors diagnose patients with Waardenburg syndrome is through

genetic testing. There are several genes involved in the different types of

Waardenburg’s. Mutations in the genes PAX3, MITF, EDN3, SOX10, EDNRB, and

SNAI2 lead to the variations found in the syndrome (USNLM, 2006).

The genes that cause Waardenburg syndrome are involved in the formation and development of several types of cells, including pigment-producing cells called melanocytes. Melanocytes make a pigment called melanin, which contributes to skin, hair, and eye color and plays an essential role in the normal function of the inner ear. Mutations in any of these genes disrupt the normal development of melanocytes, leading to abnormal pigmentation of the skin, hair, and eyes and problems with hearing.

(USNLM, 2006) Since there are different types of Waardenburg syndrome, different gene

mutations play different roles in each type. Type I Waardenburg’s is associated with a

mutation in the PAX3 gene whereas Type II Waardenburg’s is associated with a mutation

in the MITF and SNAI2 (USNLM, 2006). About 10-20% of patients afflicted with

Waardenburg’s Type II show a mutation in the MITF gene (Milunsky, 2007). Type III is

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associated with gene mutations on the PAX3 gene, similar to those in Type I. Type IV,

which is linked with Hirschsprung Disease is related to gene mutations on the EDN3,

SOX10, and EDNRB genes. These genes are not only associated with the development

of pigment producing cells, but are also a key player in the development of nerve cells in

the large intestine.

The most common mode of inheritance of Waardenburg syndrome is autosomal

dominant. Autosomal dominant inheritance means that at least one parent has to have the

gene mutation to pass on to the afflicted child. Since the gene mutation is dominant, the

parent will have the phenotype of an afflicted individual. Autosomal recessive

inheritance is seen in a few rare cases of Waardenburg’s. Autosomal recessive

inheritance means that both parents are carriers of the mutated gene but neither of them

has the phenotype of an afflicted individual. In some cases of Waardenburg syndrome,

there are no modes of inheritance. In cases like these, new gene mutations arise in the

afflicted individuals with no other family members having an afflicted genotype or

phenotype (USNLM, 2006).

PART B: I chose to research Waardenburg syndrome because when I was born, the doctors

told my parents I had the disorder. I have never followed up with genetic tests to see if

the doctors made a correct diagnosis because I have not had any major issues regarding

the disorder. The doctors were able to come to the conclusion that I had Waardenburg’s

based on a white streak in my hair. Because I had no other physical characteristics of the

disorder, they assumed I had type II Waardenburg’s which carries approximately a 70

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percent chance of hearing impairment (Milunsky, 2007). Until recently, I had basically

forgotten this tid-bit of interesting information because it hadn’t affected me in a negative

manner. Over the past few months I have noticed that I am having a harder time hearing

out of my right ear which brought forth the idea that I might in fact have Waardenburg

syndrome. I decided to do my paper on the topic so that I can learn more about it since I

have been in the dark about the disorder until recently.

There are a handful of people walking around with Waardenburg syndrome that

have never been diagnosed because they have had no reason to believe they have a

genetic disorder. On the other hand, there are also quite a few people who have been

diagnosed with Waardenburg syndrome because they have several characteristics of the

disorder that affect there life day-to-day. Since Waardenburg syndrome is frequently

accompanied with hearing loss, a doctor who is checking out the patient’s hearing loss

often spots a physical characteristic of the disorder which ultimately leads to a diagnosis.

This might be dystopia canthorum which makes the eyes appear as though they are

widely set apart or more commonly: a white forelock or total or partially different

pigmented eyes.

Some individual and family consequences associated with Waardenburg

syndrome is a potential lifestyle change. If a child is born with Waardenburg syndrome

to two parents who are also afflicted with the disorder, there will not be much of a

lifestyle change needed if all three members have the same severity of the disorder.

Depending on what type of Waardenburg’s the afflicted individual has, they might be

dealing with problems of hearing loss, joint contractures, learning difficulties,

Hirschsprung’s Disease, and/or abnormalities in physical appearance.

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If the afflicted individual has hearing loss, it will first need to be determined

whether or not both ears are afflicted and how severe the hearing loss is. Once this is

determined, there are quite a few treatments for the disability. Some treatments include

hearing aids or cochlear implants. If the hearing loss is too severe for either of those,

then the afflicted individual will have to learn sign language. For young children

afflicted with Waardenburg’s who have profound or total hearing loss born to parents

who have perfect or no severe hearing loss, this is where a lot of questions come up.

Families face decisions such as what kind of sign language to teach their children and

whether or not they should keep their children in the regular schooling system or send

them somewhere specifically for the hearing impaired (BTNRH).

Since minor joint contractures sometimes accompany cases of Klein-

Waardenburg’s, it is one more thing an afflicted individual will have to overcome day to

day. The minor joint contractures that appear are usually in the fingers and toes (Kahn,

2007). To ease these contractures, an apparatus may be used to help stretch out and

extend the muscles, ligaments, and/or tendons that are causing the contracture. If the

contractures are very minor, physical therapy should be enough to alleviate the majority

of discomfort and make day to day activities easier.

It isn’t uncommon for children born with hearing disabilities to also have learning

disabilities as well (SAHI, 2007). Because of this, it is imperative that children born with

Waardenburg’s and hearing loss get the proper medical attention as soon as possible to

figure out a plan that best suits their needs to make sure they are as successful in school

as possible.

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Hirschsprung’s Disease, associated with Waardenburg-Hirschsprung is a disorder

that affects the large intestine (USNLM, 2006). The disorder causes intestinal blockage

and constipation. This can potentially cause extreme pain and interfere with day to day

activities. In severe cases, surgery is the only way to fix the blockages such as the case of

little Tom:

Tom took the first bottle just fine and my husband loved being allowed his first hold and cuddles with his son. Tom later vomited that first feed and his tummy looked distended. The next day, vomit went from bile, then to fecal matter, he never passed meconum. An X-ray showed a bowel obstruction. We were quickly transferred to I.C.U in another hospital in New Zealand. After many tests and biopsies, Tom was diagnosed with Hirschsprung's disease. He had surgery at 6 days old for a loop ileostomy.

(MUSHC, 2007)

The most common barrier to overcome with Waardenburg syndrome is the

physical appearance barrier. Since Waardenburg syndrome is most commonly known for

hearing loss and pigmentation anomalies it is extremely common for those afflicted with

the disorder to have different colored eyes, white forelocks, and pigmentation spots on

different parts of their bodies. In more rare cases, some afflicted individuals have to deal

with cleft palate and dystopia canthorum. Although surgical procedures have advanced

enough to, for the most part, repair a cleft palate patients are often left with a scar on their

face which will not go away. As for dystopia canthorum, there is no way to fix the

appearance of the eyes being set wider apart. More commonly afflicted individuals have

a white forelock and premature graying. This could be troublesome for younger children

since other children can sometimes be rather unforgiving of people’s differences. A lot

of people with white forelocks and premature graying often dye their hair so that the

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pigmentation differences are not noticeable. As well as hair color differences, having

two different colored eyes can be rather unforgiving for younger children as seen in this

story:

Kindergarten was also the first time I noticed something was different about me – I had always been very confident (or perhaps indifferent) of my appearance. I remember holding my teacher’s hand, waiting for my bus to come, when a cheeky-looking girl came off of a bus and approached me. “What’s wrong with your eyes?” she asked, rudely, “You look so weird.” My teacher was my defender, quickly reprimanding her, but that wasn’t enough to make me forget the incident. When I came home, I asked my mom if something was wrong with me, if I really did have differently colored eyes! Apparently I hadn’t noticed it until then. I spent several hours examining myself in front of a mirror, very puzzled.

(MUSHC, 2007)

Researching Waardenburg syndrome has really opened my eyes to the disorder. I

was unaware of how severe and potentially debilitating this disorder could be because the

only symptom I have had is a white forelock until recently when I have become more

aware of some hearing loss in my right ear. I feel extremely lucky and at the same time

ignorant for not knowing the severities of this disorder.

Within the last decade a lot of organizations and support groups for those afflicted

with Waardenburg’s have been created and flourished. Prior to that, there was never a

place or way for people afflicted with the disorder to get in touch with one another and

share their stories. As awareness of the disorder grows, so does the support and research

into the causes and genetic links associated with Waardenburg’s.

I believe since the disorder is extremely rare and not really publicized the public

hasn’t done much to get involved. As the research progresses, I think the public will get

more involved in spreading the word about the disorder and become more aware of the

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signs and symptoms of the disorder. Also, as the research progresses the technology will

advance meaning there will hopefully one day be better treatments to hearing loss, joint

contractures, and Hirschsprung’s associated with Waardenburg’s Syndrome.

PART C: For the interview portion of this paper I got in touch with “Banjo” from

AllDeaf.com who is a 23 year old male from Canada who has Waardenburg syndrome

and a genetic counselor, Andrea Uscinski, who works at Brigham and Women’s Hospital

in association with the Harvard Institute’s of Medicine.

I contacted Banjo after searching through a few of the threads on the AllDeaf.com

website. Since Waardenburg syndrome causes hearing impairments in a lot of the people

diagnosed, I had a good feeling I would be able to get in touch with an afflicted

individual on this site. Although Banjo has never had genetic testing done to confirm the

diagnosis, the doctors are fairly certain he has Waardenburg’s because of certain traits he

displays. Banjo has one brown eye and one blue one, profound hearing loss, and his hair

turned gray between 10 and 12 years old. The one surprising thing to me is that Banjo

referred to these three traits as having a “mild form” of the disorder while a lot of people

out there would consider the profound hearing loss “severe”. Banjo uses hearing aids to

overcome his profound hearing loss and eye glasses to correct his vision problems.

Although teased about his premature graying hair, he shrugged off the comments as a

preteen and didn’t really think twice about his appearance. As for his different colored

eyes, he says most people don’t notice them and if they do they think the two different

colors are “cool”.

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Andrea Uscinski graduated from Brandeis University in May of 2006. Unlike a

lot of the genetic counselors I got in touch with, Andrea has actually had experience

working with those diagnosed with Waardenburg syndrome although she is extremely

new to the field.

Andrea described what exactly it is that a genetic counselor does as well as what

makes a “rare” disorder “rare”. She also explained how although one person might find

some odds rather high, another patient might think those same odds are somewhat low.

In the world of statistics and the odds of inheriting a disorder, it seems as though a lot

depends on the patient’s perspective and optimism.

Andrea then went on to give an extremely thorough explanation of diagnoses and

how they are beneficial to the patient because it helps the doctor predict what might come

next. She also mentioned the differences between a diagnosis a doctor makes by viewing

the patient and a diagnosis made by genetic testing. And apparently if I were to get

genetically tested for Waardenburg’s and the tests return positive, my insurance rates

could go up drastically or I could potentially be dropped although I have never been to

the doctor requiring medical help for the disorder. To me, this is extremely disheartening

since the people who need good health insurance are usually those that are afflicted with

disorders and diseases. If a company that is supposed to protect and help those afflicted,

doesn’t; who are these individuals supposed to turn to for help?

Andrea entered the field of genetic counseling because she prefers the relationship

formed between a patient and a genetic counselor rather than the quick “15 minutes”

usually spent between doctor and patient. She also enjoys the variety of areas to work in

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regarding genetic counseling alongside working with support groups and being able to

turn the medical jargon into digestible information for the patients.

As the conversation went on, we began to get into more of the inheritability and

genetics of the disorder. Since this is a fairly personal topic for me, I asked Andrea a few

questions about my situation and different symptoms associated with the disorder. Some

of the questions included whether or not someone can have just a white forelock with no

other symptoms and still have the disorder or whether or not all-over graying in your

early twenty’s constitutes “premature graying”. To know for sure whether or not I have

the disorder I will need genetic testing. The question now is: do I want to risk my

insurance rates for the sake of knowing?

INTERVIEWS:

Interview with individual afflicted with Waardenburg Syndrome:

‘Banjo’ from Alldeaf.com is a 23 year old from Ontario, Canada who has Waardenburg syndrome.

StudentNCSU (Chantal): How old were you when you were diagnosed with Waardenburg Syndrome? Banjo: Well, I'm not sure when I was diagnosed with it. But I'm pretty certain it was within a year of my birth date.

How did they diagnose you with Waardenburg Syndrome? (blood tests or visual characteristics) Banjo: I have different coloured eyes. One is blue and one is brown. The greying didn't begin until I was approximately 10 to 12 years old. I'm deaf, which you already knew.

Have genetic tests been done to determine which gene your form of Waardenburg Syndrome is associated with? (EDN3, EDNRB, MITF, PAX3, SNAI2, or SOX10)

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Banjo: Not that I know of, but it's a mild type. Only my eyes, hearing ability and hair are affected.

Which type of Waardenburg Syndrome were you diagnosed with? Which characteristics associated with Waardenburg Syndrome do you have? Banjo: Deafness, premature greying and different coloured eyes. It has been said the bridge between my eyes is slightly (and I mean slightly) wide. Hardly noticeable, I don't even notice it myself. I don't have a skin condition or any sort of severe symptoms associated with the syndrome.

How severe is your hearing/vision loss or do you have none at all? Banjo: I wear a pair of eyeglasses, I am somewhere near-sighted. I can walk around without eyeglasses, but for driving, I like to wear one since I see better with it. Or if I go to the movies, I wear them so the movie will appear much sharper. My deafness is severe. I cannot hear conversations without hearing aids. I can hear drums or deep-bass sounds at close range (probably 50-75ft).

How have you overcome this syndrome? Banjo: I never really took issue with it. It's a part of me. Always has and always will be.

Do you find that people are accepting of Waardenburg Syndrome (if you have visible characteristics of the syndrome)? Banjo: Actually, people rarely notice my eyes. The only obvious part would be my deafness but many aren't aware of the syndrome itself to start with. In fact, once they discover my eyes, they think it's pretty cool. When I was a teenager, some students would occasionally call me an old boy because of my hair. It really never bothered me.

When diagnosed with Waardenburg Syndrome, were there organizations established to help educate and inform you about the syndrome? Banjo: Not really. My family doctor told my parents of the syndrome and educated them a little on the subject. Then years later when I became more interested in the subject, I decided to do more research.

If you could tell people one thing that is misunderstood or not well known about Waardenburg Syndrome, what would that be?

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Banjo: Well, there has been the occasional question of if I see differently from my eyes. To answer that question, I would say no. However, I have noticed that if a sun is shining on one side of my face, once I start blinking one eye and I would notice one is more saturated while one is slightly less saturated. This only happen if the sun shine into one of my eyes. Just thought you would find that interesting.

So the doctors are not sure of what type (I-IV) of Waardenburg Syndrome you have? Banjo: I just don't recall being told which type. Plus, I don't believe most doctors are really enlightened on the syndrome to start with.

Interview with genetic counselor:

Andrea Uscinski is a genetic counselor working at Brigham and Women’s Hospital in Boston, MA. The following comes from several emails exchanged between Andrea and me:

Chantal: (from the original email I sent) Hi-

I am an undergraduate student at North Carolina State University and I am currently working on a research paper for my honors genetics class. Part of the assignment requires us to ask a professional working in the field a few questions about our topic of choice. I have chosen to research Waardenburg syndrome and I am curious if you have the time to answer a few questions regarding the syndrome?

The questions are:

What exactly is it that you do?

How long have you been in the field?

How often do you encounter/diagnose a patient with Waardenburg Syndrome?

Which type of Waardenburg Syndrome are you most familiar with?

Which type of Waardenburg Syndrome is most commonly diagnosed?

What genes are related to Waardenburg Syndrome?

How is Waardenburg Syndrome inherited?

Does Waardenburg Syndrome affect life expectancy?

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What treatments are used to treat the symptoms of Waardenburg

Syndrome?

What is the most severe case of Waardenburg Syndrome you have encountered and what were the characteristics displayed in the afflicted patient?

Thank you for your time and I look forward to hearing from you soon :) -Chantal Moshakos

Andrea: Maybe it would help to know my background? I am a genetic counselor currently working at Brigham and Women's Hospital/Harvard Medical School in Boston, MA. I received my Master's degree in Genetic Counseling from Brandeis University in May 2006 so I am new to the field. What is a genetic counselor? Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates: * Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. * Education about inheritance, testing, management, prevention, resources and research. * Counseling to promote informed choices and adaptation to the risk or condition. The above definition is the professional definition stated by the National Society of Genetic Counselors. As you can tell from the definition it is a broad field and we work with all kinds of patients...from the prenatal setting where we counsel families about their chance of having a baby with Down syndrome or Spina Bifida to the genetics clinics where we try to find diagnoses for children and adults with different conditions to areas such as cancer where we try to find out whether people or families are predisposed to having certain conditions Waardenburg syndrome is a "rare" condition but there are conditions that are "rarer". In genetics, the word "rare" takes on new meanings depending on the context. I was fortunate enough to see a lot in my internships in the Harvard teaching hospitals because people from all over the world with the "rarest" conditions go to these hospitals for their care. Even though I am new to the field, I have had the opportunity to work with a few patients with Waardenburg syndrome through my internships.

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In terms of what it is like to live with the condition, different people have told me different things. One of the surprising things in my internships is the reactions that people have when they or their children are diagnosed with a condition. Just as "rare" is a relative term, "risk" is a relative term. If someone told you that your risk of having Waardenburg syndrome was 1/2 or 50% would you think that risk was high or low? Some people might say high, some people might say low. Some people might be really worried, other people might not be so worried. I have seen many different reactions and each reaction is "correct" or valid. In your paper, you might mention your personal experience including what you think/feel about not having a "genetic diagnosis" and your thoughts on genetic testing in the future. So what is the difference between a clinical diagnosis and a genetic testing result? What is the point of a diagnosis anyway? A diagnosis is very important because it gives physicians information not only about a person's current health but it also tells them other things to look out for in the future. For Waardenburg syndrome these things include difficulties with hearing and vision. You may have had closer screening than other people because your doctor mentioned the possibility of Waardenburg to your parents when you were born. A diagnosis also gives a person access to resources that they might not have. For example, if a child had learning disabilities with no diagnosis, that child may have a much more difficult time help from special needs programs than if that child received a diagnosis such as Down Syndrome. Some diagnoses are made on the basis of a combination of major health problems and others can be made by recognizing small subtle features about a person. The key is to try to put a pattern together. For example, a "white forelock" is a small subtle feature that anyone can have and on its own means nothing. However, if you combine that feature with other features that are consistent with a disease such as Waardenburg syndrome, a doctor may give you a diagnosis. Does this mean for sure that you have Waardenburg syndrome? That is something that your doctor will have information about based on your personal medical history and your family history. It is possible for a person to have a "white forelock" and some hearing loss without having Waardenburg syndrome. It is also possible for a person to have this condition even if no one else in their family has the same condition. Many times genetic testing is used to confirm a diagnosis. Genetic testing is not for everyone. It is a personal decision to get tested and only one that you can make. Some people like to know...information gives them power...other people are overwhelmed or scared to find out they have a condition, especially if they are feeling fine. It is something to discuss with your family and doctor. If you wanted to pursue testing, you would probably end up talking to a genetic counselor who would be able to review your medical and family history and discuss the pros and cons with you in detail. It would still be up to you to decide.

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Of note, a genetic test result for a condition like Waardenburg can potentially affect your insurance rates or coverage. Once a genetic test result becomes a part of your medical record, insurance companies can look at it and decide to increase your rates or drop your coverage. That would be something to talk to a genetic counselor about in your area who would know the way that works in your state. Chantal: It seems the more I think about the disorder, the more questions arise in my mind: You mentioned you have worked with a few patients with Waardenburg's, which type of the disorder did they have? Andrea: A couple had type I and a couple fell into the "Waardenburg spectrum" meaning that they had some of the features but either did not want to pursue genetic testing or genetic testing did not identify a known mutation. Chantal: Also, what drove you to choose a career in the field of genetics? Andrea: I chose genetic counseling because I love helping people and I enjoy the counseling and teaching part of medicine the most. Whereas doctors often only have 15 minutes with a patient, I talk with patients for an hour or more and get to develop a real relationship with the people I work with. It is a very interesting field and a very broad field because they are so many different areas that you can work in. I have always enjoyed science and I can translate complicated medical terms into language that is meaningful and relevant for different people. I also love working with support groups, serving as a patient advocate, and helping patients and families access resources. Chantal: Genetests.org says premature graying, graying before 30, as a sign of Waardenburg's. My Mom was all over gray by the age of 23, and I am 21 and starting to go gray. Could this be an indicator that maybe she is a carrier of the disorder although she has no other symptoms? Andrea: It is possible that she is a carrier...but her doctor should be the one to diagnose her... Chantal: Also, she has SUPER sensitive ears and loud noises really bother her do to pain. Are there any cases of Waardenburg's causing hypersensitivity in the ears or does it only cause a loss of hearing? Andrea: Waardenburg syndrome is usually associated with a loss of hearing but that doesn't mean that there aren't exceptions...again, if she asks her doctor about this he/she may be a better person to consult as her doctor is more informed about her hearing.

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Chantal: Can someone have a white forelock without having Waardenburg's syndrome? Andrea: YES...many people have white forelocks and many people also have premature graying and most do not have Waardenburg syndrome Chantal: Can someone have Waardenburg's and only have a white forelock and no hearing loss or other symptoms? Andrea: It depends on how you define Waardenburg syndrome...many people have white forelocks and no hearing loss or other symptoms...this does not mean they all have Waardenburg syndrome....do they have a mutation in PAX3? Who knows...it might be a good study... Chantal: Can hearing loss occur later in life progressively? What is the chance of this occurring for someone with Waardenburg's? Is it imminent that this will occur at some point in their life? Andrea: People with Waardenburg syndrome have different degrees of hearing loss...see the following article for more info: http://www.nidcd.nih.gov/health/hearing/waard.asp Remember, that the features described are often the features that people share in common, but there is a range and people are not exactly the same. Chantal: Is it possible for someone to have Waardenburg's and not know it? Can someone have the disorder and have no symptoms? Andrea: Again, it depends on how you define Waardenburg syndrome...does it matter at that point if they do or not? If they have no symptoms, they will never come to medical attention. Chantal: Are there any medications or treatments that prevent or slow down symptoms from developing? Andrea: I think it discusses this in the gene reviews on www.genetests.org Chantal: How do the mutations in the certain genes lead to the different types of Waardenburg's? Andrea: Ah...now you are getting into the true science...you might be able to find out some of that info on Pubmed...but I don't think your teacher will expect you to be able to answer this question....there are researchers dedicating their whole lives to answering this question...but you are right in thinking that different mutations in genes affect the function of the gene differently....our genes serve as the instructions for the body to carry out is many functions...variations in other genes may modify the effect of gene changes as well (which we also do not know too much about) and may act protectively against the condition or may enhance the effects of the condition.

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Chantal: If a case of Waardenburg's is not directly inherited, what causes the gene(s) to mutate leading to the disorder? Andrea: This is not known yet...scientists are working to figure it out...but this case is called "sporadic" or a caused by a "new mutation"....this just happens to our genes...sometimes it has no effect on our health and other times it does...this is part of the reason that there are differences and variation in life... Chantal: When someone comes to you for counseling and they (one or both parents) has Waardenburg's, what advice do you give them about planning a family? Andrea: I find out what they know about the condition already...try to fill in any information gaps...and ask them what their questions/concerns are...as i mentioned before, everyone is different and everyone handles things differently...I don't tell them what to do...I only give them the information and support that they need to make a decision that is best for their particular situation...I also help connect families to other families, support groups etc. Sometimes people want to talk to others who have been in the same situation, hear their stories, and find out how they made their decisions. Chantal: I have been in contact with someone who has Waardenburg's. He has a white forelock (but is now completely gray) and one blue and one brown eye. He is also deaf. The doctors never told him what type of Waardenburg's he has. He has mentioned that when the sun is shining on his face, when he blinks one eye at a time, he sees through one eye with more saturation and through one eye with less saturation. Are vision problems associated with Waardenburg's? Andrea: Yes...you will probably find out more about this in your research...I think I have a few pictures I might be able to dig up for you on this one... Here is an article you might check out: Pediatr Ann. 2007 May;36(5):277-8.Links Different colored eyes. Waardenburg syndrome. Charrow J. Division of Genetics, Birth Defects, and Metabolism and the Genetics Laboratory at Children's Memorial Hospital, Chicago, IL 60614, USA. jcharrow@northwestern.edu You can email the author for a copy of the paper Chantal: I hope I am not bombarding you with too many questions? I am just completely fascinated with learning more about this disorder. Andrea: You have asked a lot of good questions...I'm happy to help...

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References: Title Page Images: Ghorayeb, Bechara Y. Otolaryngology Houston. 26 Aug. 2007. 25 Oct. 2007 <http://www.ghorayeb.com/Waardenberg.html>. Karaman, Ali., and Cihangir Aliagaoglu. Waardenburg Syndrome Type 1. 2006. 25 Oct. 2007 <http://dermatology.cdlib.org/123/case_presentations/waardenburg/karaman.html>. PART A: Ezzell, C.. "Hearing Gene." Science News 141.18 (1992): 296-297. McKusick, Victor A. WAARDENBURG SYNDROME, TYPE III; WS3. 29 Mar. 2006. 25 Oct. 2007 <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=148820>. Milunsky, Jeff M. Waardenburg Syndrome Type I. 19 Apr. 2007. 25 Oct. 2007 <http://www.genetests.org/servlet/access?db=geneclinics&site=gt&id=8888891&key=HO49awy6QiCQl&gry=&fcn=y&fw=H5h2&filename=/profiles/ws1/index.html>. National Institute on Deafness and Other Communication Disorders (NIDCD). Waardenburg Syndrome. 16 Apr. 2007. 25 Oct. 2007 <http://www.nidcd.nih.gov/health/hearing/waard.asp>. Polzin, Scott J. Waardenburg Syndrome. 2002. 25 Oct. 2007 <http://www.healthline.com/galecontent/waardenburg-syndrome#waardenburgsyndrome>. Tagra, Sunita et al. "Waardenburg Syndrome." Indian Journal of Dermatology, Venereology & Leprology 72.4 (2006): 330-333. U.S. National Library of Medicine (USNLM). Waardenburg Syndrome. Apr. 2006. 25 Oct. 2007 <http://ghr.nlm.nih.gov/condition=waardenburgsyndrome>. PART B: Boys Town National Research Hospital. Information on Hearing Loss - My Perspective as a Deaf Person Working with Geneticists.. 25 Oct. 2007 <http://www.boystownhospital.org/Hearing/info/genetics/perspectives/my_perspective.asp>. Kahn, Alice. About WS. 2007. 25 Oct. 2007 <http://www.units.muohio.edu/waardenburgsyndrome/aboutws.htm>.

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Miami University's Speech and Hearing Clinic. Story From A Teenager with WS. 2007. 25 Oct. 2007 < http://www.units.muohio.edu/waardenburgsyndrome/teenagerstory.htm>. Miami University's Speech and Hearing Clinic. Tom's Story. 2007. 25 Oct. 2007 <http://www.units.muohio.edu/waardenburgsyndrome/toms.htm>. Society to Aid the Hearing Impaired. Hearing Impairment Problems and Solutions. 2007. 25 Oct. 2007 <http://sahiearcare.org/hips.htm>. U.S. National Library of Medicine (USNLM). Waardenburg Syndrome. Apr. 2006. 25 Oct. 2007 <http://ghr.nlm.nih.gov/condition=waardenburgsyndrome>.