Interview with Alice Kahn, Ph.D., CCC-SLP, Associate Professor in the Department of Speech-Language Pathology at Miami University in Oxford, OH, & Author of Waardenburg Syndrome (2007)

Linda Schreiber: I'm speaking with Alice Kahn today about Waardenburg syndrome; a scarcely known syndrome, but one that speech-language pathologists should be aware of. Good afternoon Alice.Alice Kahn: Good afternoon Linda.Linda: Alice, tell us about your background and how you became an expert in W

Linda Schreiber: I'm speaking with Alice Kahn today about Waardenburg syndrome; a scarcely known syndrome, but one that speech-language pathologists should be aware of. Good afternoon Alice.

Alice Kahn: Good afternoon Linda.

Linda: Alice, tell us about your background and how you became an expert in Waardenburg syndrome.

Alice: I graduated from the University of Houston and I worked a few years at an Easter Seals Society. Several years later, I began teaching at Northeast Louisiana University, and consulting at Delhi Guest Home, a residential facility for adults who were cognitively disabled. During work there, I noticed that many residents were not only cognitively disabled, but that they had unusual facial features. The facility administrator was a dentist and he taught me some things about facial anomalies and their relationship to eating, facial growth, swallowing, and speech.

I realized I needed to know more about anatomy and its relationship to speech and so when I pursued my PhD, I was able to complete a portion of my PhD training in medical school under the guidance of the head of the department of dentistry and prosthodontics. Dr. G.A. McCarty, Jr. was a well-known prosthodontist in the Mid-South, and he taught me how teeth impact the growth and development of the face.

When I began teaching at Miami University of Ohio and began seeing patients again, I started observing unusual facial features in patients with hearing loss. Many of the patients were of German background--and that makes sense when you think about how genetic conditions are passed on a lot of times into ethnically related families. So what I was seeing I think, were a lot of people with Waardenburg syndrome, who were distant relatives, who had immigrated from Germany, and then settled in the Southwest Ohio area.

Linda: And that sparked your interest in Waardenburg syndrome.

Alice: I began to study Waardenburg syndrome, mostly the hard core research, genetic causes, and what could be done about it. I found that very little was known about it from a speech-language pathology point of view. Basically, that's what got me started. And with the help of the audiologists at Miami University, we've been establishing backgrounds and records and keeping track of four or five families.

Linda: Let's talk about the syndrome and the characteristics that define it.

Alice: Waardenburg syndrome (WS) is a rare disorder that results from an autosomal dominant mutation as a deletion in the Pax-3 gene. Some of the characteristics include pigment anomalies, deafness, and defects in the neural crest derivative tissue. In 1951, Waardenburg defined the main features of the syndrome as:

• a prominent broad nasal root
  
• a connection of the medial part of the eyebrows (unibrow)
  
• a white forelock
  
• two differently colored eyes in the same individual (one usually brown and the other bright blue)
  
• deafness

Linda: How prevalent is the syndrome?

Alice: An estimated 1 in 4000 individuals are born with WS. WS occurs in all races, and occurs equally in males and females.

Linda: So what's the probability that the genes for Waardenburg syndrome are passed to one's offspring?

Alice: For most types of WS, if someone who has the gene mates with someone who doesn't have the gene, there is a 50-50 chance of the child having WS. And the effects of the syndrome can be very mild or very severe, with the full-blown spectrum of characteristics. And if someone has the syndrome, he or she may have a problem of pigment distribution throughout the human body, including pigmentation to the eyes and skin. And importantly--and we can't see this--it affects distribution of pigment to the inner ear, and that pigment is necessary for the inner ear to function properly. If the inner ear doesn't have that pigment, that person will be deaf or severely hearing impaired.

And as I mentioned, some of the other major signs are eyes of two different colors; bright blue eyes; a streak of very white hair--like a skunk stripe--usually located in the center of the forehead; and very white patches of skin on areas that should be pigmented. And as you can imagine, this is more observable in someone who would normally have a dark skin color, such as a person who is African-American or who is from India as examples. Also, you don't expect white hair or blue eyes in a person who typically has brown eyes or brown hair or black hair.

Linda: Of course, the feature to be most concerned about is the hearing loss.

Alice: Yes, the person with WS may appear to just have the characteristics of bright blue eyes and some of the facial features, but he or she also needs to have a hearing test frequently because the hearing loss can occur at any time; it's not always present at birth.

Linda: So this genetic syndrome may or may not have hearing loss associated with it. What is the incidence of hearing loss?

Alice: There are four types of Waardenburg Syndrome. Type 1 is characterized by displacement of the folds in the eyelid; hearing loss occurs in 20% of individuals with Type 1. The incidence is about 1/40,000. Type 2 is more frequent than Type 1 and Type 2 has a higher frequency of deafness; hearing loss/deafness occurs in 50% of those manifesting WS Type 2.

What's interesting is that you would think patients would know they have the syndrome; but they often don't. They may know they have a hearing loss, but they often do not recognize a relationship between their hearing loss and how they look or how their eye color may be different, etc. It's one of those syndromes where some of the features look quite attractive and people are proud of them.

Linda: And it seems the characteristics of WS vary.

Alice: Yes. Each time a person is born with this gene, the characteristics of the syndrome can be different. Which features will the gene affect? Will it affect distribution of color? Will it affect pigment to the ear? Will it affect pigment to the eye? Will it affect the growth of their face? Or will it affect all of them? In one type of Waardenburg's, the eyes appear wide set and the person looks like they have Asian ancestry. That's just in one of the types and in other types they may have perfectly typical-looking eyes and facial features. The bottom line is that individuals in our profession need to recognize the features, and when we see them, alert the person or the family about hearing loss and suggest an audiological examination.

Linda: And you mentioned that those audiological exams need to occur sporadically because the hearing loss can occur at any time.





Alice: Yes it can. Of course, you would want to find out immediately at birth if there is a hearing loss and you do that through Otoacoustic Emissions testing, which is a routine test given to newborns. When we know families who have the syndrome will have a new baby, we suggest that they bring the child in for the exam as soon as possible. The exam tells about the integrity of the inner ear hair cells. Children with WS can be born deaf; born without hair cells in the inner ear, or they can be born without a cochlea.

Linda: So if a speech-language pathologist is aware of the genetic history in a family, he or she would want the family to be aware of newborn hearing screening. But there will also be families who won't be aware that they have that genetic link to Waardenburg syndrome, correct?

Alice: That's right. One of my best friends here in Oxford is deaf in one ear and when I met her we talked about her hearing loss. And she said everybody in her family had a hearing loss: her mother did, her grandfather did, etc. I said, "Yes, and you have blue eyes and you have a white patch in your hair." For her, the syndrome could be traced for four generations. And I explained that her children (who are now adults) were at risk for hearing loss. We tested all four of them. Some of her grandchildren have other signs, not hearing loss, but some intestinal problems that are also characteristics of Waardenburg's. Very rarely, and in this family unfortunately, you'll see children born with cleft palate or spina bifida. My friend's family had a history of these problems and also miscarriages. Her mother had delivered a child with spina bifida, who later died, and also had a child with cleft palate. And in cases like this, a genetic counselor could identify the presence of the syndrome.

Linda: Do you see cognitive problems as a result of the syndrome?

Alice: No. Typically, cognition is not a factor unless the individual has had a neglected profound hearing loss and hasn't received the help needed, then he or she might have language-learning problems. But that's related to the hearing loss and not to a cognitive disability.

Linda: You mentioned several times the connection to German and Turkish ancestry. Is there really an ethnic link?

Alice: I've seen the syndrome in Italians and Asian Indians too. It does run in families only because people tend to marry people like themselves, that is, Germans marry Germans and Italians marry Italians. So if there is a gene, the gene pool is narrowed and when the gene pool gets narrow you have more chances for all the cards being dealt with Waardenburg's written on them.

Linda: Alice, it seems that science is at a point where this syndrome can be identified genetically with fair accuracy.

Alice: With Types 1 and 2 that's true. With the other two types that's not true. They haven't yet identified the location of the genetic errors for Types 3 and 4, and they have only recently located the Type 2 error.

Linda: You've mentioned earlier that speech-language pathologists and audiologists need to know about this syndrome, not just for the intervention component, but for the diagnostic component as well. In particular, professionals need to educate clients about the hearing loss factor and the need for consistent and frequent hearing exams.

Alice: I'm almost fanatic about this. I think it's really important that speech-language pathologists realize that we're heading in a direction that's going to require more and more of us to know the genetic pedigrees of families. That is our job. In the past, we might have thought that's the geneticist's job. Nope, it's also ours. When you refer someone to a physician, the physician will want some verification of why you sent the person and why you think there may be a syndrome involved. A family history is a good way to gather this information; that, as well as a description of his or her physical appearance. And sometimes you're going to have to spell it out for the doctors because they're not always aware of this syndrome either. Several of my parents have said, "Well my pediatrician didn't tell me my child had Waardenburg's. He said, 'Isn't that cute. Your baby has two different color eyes.' "

Linda: Alice, you have written a book, Waardenburg Syndrome, published by Plural Publishing. It's complete with a full description of the different types of WS, how to diagnose WS, how to counsel families, and more. It includes colored photographs depicting the characteristic facial features that accompany the syndrome. And you have clearly described treatment issues for patients with WS. For readers who are interested in learning more about the syndrome, this is a wonderful resource.



Alice: I have also gotten my students involved in helping me build a website for helping Waardenburg's patients and that website has brought together people with WS from all over the world. The web was just a godsend; a lot is known about the syndrome genetically, but not much is known within our profession about recognizing the syndrome and the website can also help SLPs become more aware.

Linda: I hope folks will check out the website: www.units.muohio.edu/waardenburgsyndrome/index.html
It's very user friendly and offers helpful resources and links.

Alice: Well thank you.

Linda: Alice, thanks for educating us today on the topic of Waardenburg syndrome.