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Monday, January 30, 2012

Usher syndrome part IV: Clinical management and research directions

by Jennifer Phillips, Ph.D.

Editor's Note:  This is part four in a series.  Here are the links to parts one, two, and three. We will return to the story of Bella's struggles in school in the next post.

The current standard of pediatric care mandating that all newborns undergo hearing screenings has been applied successfully throughout the industrialized world. Early identification of hearing impairments gives valuable lead-time to parents and health care providers during which they can plan medical and educational interventions to improve the child’s development, acquisition of language skills, and general quality of life.

Some percentage of children born with hearing loss have Usher syndrome. Until fairly recently, a diagnosis of Usher syndrome as distinct from various forms of congenital hearing impairment was not made until the onset of retinal degeneration was clinically documented—usually years after birth. The considerable number of genes involved made genetic screening impractical with the methods used up until the last few years, so unless there was a family or community history that could shorten the list of targets by implicating a particular Usher gene or subtype, there just wasn’t enough data to proceed.

Considering that educational and medical intervention designed to impact a deaf or hearing-impaired child’s cognitive and social development vary considerably based on whether the child in question is expected to lose his or her vision later in life, an earlier diagnosis of Usher syndrome has been a critical research goal ever since the breadth of the Usher gene list has been known. The most impacting diagnostic advance in the past decade, with respect to earlier identification of Usher children, has been gene chip screening. With this technology, the patient’s DNA can be screened against a microarray of human genes known to cause deafness (and/or Usher syndrome) when mutated, and variances in the DNA sequence of any screened gene would be detected and analyzed. While groundbreaking, there are still some limitations in the availability of this analysis, although hopefully that is a short term problem. A more pervasive problem—ultimately solvable, but on a much more protracted timeline—is the fact that we still can’t screen for everything. The genes on the chip usually represent the most common mutations, so if a patient has a rare or unmapped type of USH, it won’t be caught by this assay. Searching for new genes, and new variants of known genes to add to the list is an important focus of ongoing research. Developing improved methods of early screening for hereditary vision defects is another.

In spite of the considerable amount of information about the biological cause and clinical progression of Usher syndrome obtained over the past 10 years, there are, as of yet, no treatments available based on the molecular underpinnings of the disease. Following the diagnosis of hearing impairment in an infant or child, the parents may consider hearing aids or, in cases of profound hearing loss, as is common in most Usher type I patients, a cochlear implant. The timing of the installation of these devices is critical, as speech development can be significantly impacted if the child does not begin to hear and reproduce spoken sounds in the first year or two of life. Obviously, early diagnosis is critical to the success of this intervention.

In cases where hair cells are severely affected by disease, traditional hearing aids, which merely amplify sound, are ineffective. Cochlear implants are surgically placed devices that can substitute to some degree for defective hair cells. An implanted processor converts the sound signals it receives into electrical impulses and transmits them directly to the auditory nerve, via wires threaded through the cochlea, basically fulfilling the role of the missing or defective auditory hair cells. Here’s a short video of the placement and mechanism of action of this device:


And here is a link that contains several audio files simulating how speech might sound through a cochlear implant.

There is currently no treatment for the vision loss suffered in Usher patients. The first sign of a vision problem usually occurs when patients report difficulty seeing at night—a symptom of rod photoreceptor loss in the periphery of the eye. Degeneration of the remaining photoreceptors usually occurs from the periphery inward, resulting in an increasingly restricted visual field. The rate of retinal cell death is monitored through regular ophthalmological examinations, and although some physicians recommend dietary supplements in an effort to slow the progression of photoreceptor degeneration, there are no targeted therapies, either preventative or curative, available.

Currently, the most tractable possibility of a treatment for the retinal disorder lies in gene replacement therapy. There have been encouraging results using viral vectors to deliver functional copies of genes into retinal cells of mouse models and of humans in research trials (just type “gene therapy” into the Usher Blog’s search engine to read about some recent examples). The use of nanoparticles as a delivery system should be another fruitful avenue of research. The slow, progressive nature of the retinal degeneration in Usher patients lends itself to the application of such treatments. In principle, an effective therapy initiated early enough could begin rescuing photoreceptors from dysfunction and eventual death prior to the onset significant vision loss, further underscoring the importance of developing methods for early diagnosis.

Ongoing research into where and how the Usher proteins function in auditory and visual cells will be important in determining the optimal target for gene replacement therapy, and animal models of the disease will continue to be indispensible both for basic study of the molecular and cellular physiology of Usher syndrome as well as for the testing of new therapies in preparation for clinical trials. We will continue to report on the latest developments in this research here on the Usher Blog as results come to light.

Friday, January 13, 2012

The Bella Chronicles, Part II: The Search for the Source

By Mark and Bella Dunning

My daughter, Bella, is thirteen years old and a good student. She has always loved going to school and was one of those kids that teachers described as a joy to have in class. She is even tempered and rarely gets upset.

So why was she crying every day before school?

In the first part of this series I wrote about Bella’s history in detail and why it was such a surprise that she was suddenly having problems in school. In this post, I will write about our search for the source of her problems.

One more quick point: I worked on this post with Bella. I wanted to make sure she was comfortable with the content, and, in truth, it gave me a chance to check in with her. I wanted to make sure we hadn’t missed anything, but also Bella’s answers and her reaction were telling. She liked the idea of having input on the article, so you’ll see her name in the byline. I wrote it but she read it and contributed, too.

So what was the problem?

Our first thought was bullying.

This is Bella’s first year in middle school. Girls are tall and gangly. Boys are getting their first whiff of testosterone. Everyone is self-conscious and some try to point out the faults of others to distract from their own.

Bella would seem an easy target. She is different. Though she is blond and beautiful, she has Usher syndrome. She wears cochlear implants and glasses. She can be clumsy and has problems seeing in low light. The school has made accommodations for her, which is good but which sometimes make her stand out. She doesn’t have to attend gym. She has an FM system in class. There is a hand mike that the kids pass around when they ask questions.

Bella’s middle school is a regional school. Six elementary schools come together there. The grade school kids in Bella’s old school have grown up with Bella. They have been passing the hand mike since before they can remember. There was always a kid in class with cochlear implants. To them it was normal. But to the kids from other schools it had to be different. Were they picking on Bella?

When I asked Bella, she made a face that said the very idea was foreign to her. “The kids treat me like all the other kids,” she said, as if that were expected.

But were they embracing her?

That was the next idea. Was Bella simply lonely? The other kids were not picking on her, but perhaps they were isolating her. She is thirteen and thirteen-year-olds swirl with hormones. All the kids want to be the same and Bella is different. What if she was feeling left out?

Having Usher syndrome can be very hard socially. The hearing loss is the hardest part. Kids miss out on pieces of conversations. They hear the other kids laugh but they missed the joke and it’s awkward to ask to have it repeated. Often they tire of straining to hear the conversation, so they don’t bother any longer. They just laugh when others laugh and agree when others agree all the while slowly glazing over. Everyone gets up to go somewhere they all agreed to go, but the kids with hearing loss stays, not sure of the destination or the invite.

Some kids with hearing loss take the opposite approach. They hijack the conversation. If they are always the one talking then they always know what is being said. But that, too, can be socially isolating. Kids tire of the one man show and make plans that don’t include the kid that talks too much.

In middle school there is no recess. Socializing occurs in the cafeteria. The cafeteria is constructed like a hangar, with high ceilings, tiled floors, metal appliances and folding tables. It’s built for cleaning up after four hundred sloppy students, not for acoustics. Bella couldn’t hear a thing. So the school allowed Bella to have lunch in a conference room next the nurse’s office. They thought Bella could invite a friend or two to lunch so she could be involved in the conversations.

Bella brought nine kids with her the first day. Social isolation was not her problem.

“The nurse’s office is good,” she says, “I can hear everybody. I can see everybody better because in the cafeteria it’s darker. And my friends don’t mind going to the nurse’s office for me. They think it is fun.”

In the background of all of this, the Penn State and Syracuse abuse scandals were playing out. So another possibility was more sinister.

Was Bella being abused?

Let me take a moment to say Bella is NOT being abused and we have no reason to suspect she is. But when Bella was behaving in a way that is completely out of character, we had to consider all sources, no matter how unlikely, especially knowing what we know now about places like the Catholic Church (we’re Catholic) and Penn State. Being deafblind, beautiful, and innocent might make Bella an inviting target.

So we tried to think of places where Bella was alone with adults or older kids. There weren’t many. The only place where she was alone for any significant time was the farm where she rides horses and that didn’t fit the profile at all. Bella wanted to go the farm. It had been Bella’s oasis during her tough time at school. It was the one place she wanted to go more than anywhere else. This was not a kid afraid of abuse. On the contrary, this was her sanctuary.

When we hinted at the farm as a source of concern to Bella, she again thought we were crazy. “Everybody over there knows me and they are all good people,” she said, “They take care of me. They would never hurt me.” The farm remained above reproach in her mind and remains there in ours as well. We’re lucky to have it.

When we further examined her schedule, we couldn’t find any other time or place where even the most opportunistic abuser could have been alone with her.

No, Bella was not being abused.

Maybe it was the opposite. Maybe Bella was in love.

Was Bella having trouble with a boyfriend?


Uh, no. She was not. Bella does not have a boyfriend. She is open and honest, if a little shy, about her crushes.

“You’re embarrassing me!” she said.

We asked if maybe there was a boy she liked who didn’t like her back. Or maybe a boy who she thought liked her who later gave her the cold shoulder. We probed every angle of puppy love to see if we could find evidence of a broken heart. But Bella still likes horses more than boys, for the moment. (“Horses or boys?” I asked. “Horses. Not even close.”) That will change at some point. It just hasn’t yet.

A lot will change for Bella in the next few years. She is full on into puberty now. Her body is changing and the hormonal shifts are startling at times. I have been writing for years about my phobia of having a thirteen-year-old daughter. Well, the time has arrived and it is everything I dreaded and nothing like I imagined at the same time.

There was a point this summer where I feared for the life of my ten-year-old son. His mere scent was enough to ignite the normally placid Bella. And, of course, being a younger brother, he took every opportunity to set her off. She was his own personal firecracker and he lit the fuse every chance he got.

On the flip side, Bella has moments of maturity that are just as startling as the moments of fury. You can hold a thoughtful, adult conversation with her now as this post can attest. At a party on New Year’s Eve, she didn’t go downstairs with the kids right away. She sat at the table with the adults until the topics became too boring (which was pretty quick).

So maybe it was just the hormones and puberty themselves that were the cause of Bella’s problems.

Bella has had her highs and lows with her entry into adolescence, but that’s why we ultimately dismissed it as the cause. Puberty is peaks and valleys, yet her problems with school were a constant. She got upset every morning. Hormones may have been contributing, but they were not the cause. The problem was too consistent.

There was one other possibility that we examined and quickly dismissed. Maybe Bella was just faking it. Maybe she had decided that she preferred to be home and had learned that if she made enough of a scene, she could eventually get sent home.

Was Bella purposely crying her way out of school?

As I wrote in the last post, she was clearly feigning illness to get out of class, but that’s not what I mean by purposely crying her way out of school. I don’t mean she was so scared or upset that she didn’t want to go. I mean what if she was NOT really scared or upset but instead had decided she preferred being home and was pretending to be scared and upset so she could stay home and play video games or watch TV or do something else. What if she just wanted to play hooky?

This feels almost crazy to write if you know Bella. It’s completely out of character for her. Indeed, nothing brought a more vigorous denial from Bella than the suggestion she was faking it. She got upset to a degree rarely seen.

“You always make me feel like I’m faking it and I’m NOT,” Bella said, “I like school. I want to learn stuff. I’m not like Jack.”

Jack is her little brother and he agreed with a twinkle in his eye as he played his video game that he would fake it. All kids are different. Bella is a kid with a real problem at school and the suggestion that she didn’t have one sent her to an extreme level of frustration. No, Bella was not faking it just to get out of school.

So what was the problem?

Well, it’s complex but it comes down to two things. Bella does not have a relationship with her teachers this year. It’s not a bad relationship or a good relationship. It’s no relationship. Because she has no connection with her teachers, Bella is uncomfortable advocating for herself. As a result, she has gotten increasingly frustrated at school. Finally it reached the boiling point and spilled over in tears.

Having Usher doesn’t help. She assumes she is missing information. She assumes she is having a harder time than the other kids. These points are probably fair. She does miss information and have a harder time. But she also assumes that means she is doing worse in class than the other kids. She is not. In fact, she’s a solid ‘B’ student which in this school really is above average. Given her situation, that’s quite remarkable. I’ll go in to the advocacy problem more in a future post.

But here’s the second issue. Bella puts a lot of pressure on herself. That is in part because she is very empathetic and wants to please others. It also has its roots back in San Diego at the Classy Awards and right here in the blog. Not many kids have numerous blog posts dedicated to them or are recognized as they walk the streets of a city on the other side of the country. Bella knows that a lot of people look up to her and she doesn’t want to let them down.

“I feel like everyone is disappointed in me,” Bella said, her eyes glistening.

That’s my fault and it will be the subject of the next post.

Thursday, January 5, 2012

The Bella Chronicles, Part I: The Symptoms

by Mark Dunning

I haven’t been very active in writing for this blog recently. There are a lot of reasons involved, but the biggest has been my daughter, Bella. She’s been having a tough time. I have spent a good amount of time trying to help her, which is part of the reason I have not written lately. But her problems have also shaken my confidence considerably. It’s hard to feel worthy of sharing your knowledge about Usher syndrome and parenting when you feel like you are doing a lousy job.

Bella’s life is a frequent topic in this blog, in large part because without her, there is not blog. But she also provides very relevant subject matter. She is, in a lot of ways, a success story. Her vision hasn’t changed noticeably in several years. Her grades are on par with her hearing peers. She has lots of friends. She is a model Usher kid. It seems that everything is going great.

Except, it isn’t.

Until recently, Bella cried every day before she went to school this year. Every day. When she was in school, she had trouble staying in class. She has been to the nurse’s office 50+ times this year. This is completely out of character for her and extremely puzzling to all that know her. Clearly, something has gone wrong.

Over the next several posts I want to take you through the whole story because I think it will be valuable for other parents to hear it. You can learn from what we did right and what we did wrong. But let me set your mind at ease up front. The source of Bella’s problems at school are nothing sinister. There is no abuse or bullying or anything untoward. She’s just a 13 year old girl going in to middle school who happens to have Usher syndrome. That’s enough of a reason for her to have a hard time in school and that’s the point.

Bella attends a mainstream public middle school. She is profoundly deaf, but she has two cochlear implants. She understands sign language, but has chosen to use spoken English primarily for communication. She speaks nearly flawlessly, with no deaf accent, though she does still struggle with some words (which her little brother takes great joy in pointing out).

Bella has always loved school. She has been popular with the other kids, active socially, and a solid ‘B’ student. She rarely complains about homework and has always been quick to advocate for herself. Her situation has required some accommodations, of course. She still attends speech therapy sessions in school, though it is mostly for vocabulary preview at this point. Given her vision and balance issues, she does not attend gym. She rides horses regularly so we are not worried about her fitness. She uses the period when she would have had gym for either speech therapy or as a study. Often she gets help in the study with material she may not have understood in class.

Socially, Usher syndrome can be isolating at times, but Bella has never had a problem making friends. She has always been comfortable explaining to people that she is deaf and asking them to repeat something she missed. She has friends who are happy to guide her in situations where she has difficulty seeing. The cafeteria can be loud and difficult for a kid with hearing loss, so the school has made an effort to accommodate her socially by offering up a conference room in the nurse’s office for lunch. They expected Bella to invite a friend or two to join her there. Nine kids showed up. Bella is not short of friends.

She has some of the best professionals in the world involved in her education. Honore Weiner and Tracy Evans Luiselli have (sorry ladies) several decades of experience educating kids. Honore is currently the Education Director of the Decibels Foundation and spends her days consulting with multiple school systems on how best to accommodate kids with hearing loss. There’s no one better at what she does. Tracy is the Director of the New England Center Deafblind Project. She has spent her career helping families deal with Usher syndrome, particularly kids in school. Again, there is no one better at what she does.

Honore and Tracy have followed Bella for years and have spent hours working with her teachers to address Bella’s needs. For the most part, the teachers have been very receptive of the advice. Her school seems to be genuinely interested in accommodating her needs. Occasionally the bureaucracy is slow in delivering, but there has been little pushback about giving her what she needs to do well, both in terms of scheduling and technology.

At home, my wife, Julia, and I are actively involved in Bella’s life. Julia works at the Minuteman Arc Early Intervention Program for Children with Hearing Loss so she spends her day working with kids with hearing loss. I’m the Executive Director of the Coalition for Usher Syndrome Research. We have access to most of the world’s experts on the disease. We have many friends with Usher and we work closely with professionals who help kids with Usher in school. So we as parents are well versed in the issues facing a kid with Usher and hearing loss.

Bella herself is well versed in her condition. She has worked with mobility specialists and has been trained on how to advocate for herself, which historically she has done quite well. (Too well at times. She’s a big advocate for herself around the house when it suits her.) Finally, she has attended several Usher Syndrome Family Conferences where she has made many friends and has learned a lot about the condition.

Bella has been actively involved with the Decibels Foundation for many years. Julia and I founded the organization so her involvement was not voluntary, but she seems to have enjoyed it. She is always asking about upcoming events and genuinely likes working with the young kids in the program. As I have written before, her sixth grade class ran an event for the Decibels Foundation last winter for which they received national recognition. Bella was very proud of her class and her friends, but looking back, it was also the first sign of trouble.

The Classy Awards were held in San Diego in early September. We live outside of Boston so we had a long flight. We left on a Thursday so Bella missed two days of school. It was early enough in the year that there was not much content being discussed. It was mostly orientation. She got the homework and was able to finish it on the plane. The missed time seemed unlikely to put her far behind.

The event in San Diego was attended by several hundred people and they all stayed in the same few hotels. So when we walked through the lobby or along the streets in the area, Bella was often recognized by people she had never met. This isn’t all that new to her. As I said, she is actively involved with events for Decibels and is well known in the Usher community. She is used to being greeted by people she has never met before. Still, she was a minor celebrity and I needled her about being famous.

Her reaction was not what I expected. Bella has always been buoyant and even tempered. She doesn’t get rattled and always maintains her sense of humor (well, unless her little brother is involved). But that wasn’t Bella in San Diego. She was not excited about her celebrity or embarrassed by it, the two most logical reactions. She wasn’t overwhelmed, either, though that would be understandable, too. Instead, she just seemed weary, as if she were carrying a great burden.

“I don’t want to be famous,” she said one evening with such sad conviction that I promised her she would never have to attend another event unless she chose to. She’s thirteen, I told her, and old enough to make those decisions.

When we got home, Bella came down with a heavy cold. She missed another couple of days of school. She was probably fighting it in San Diego, so that seemed to explain her weariness. When she was healthy enough to go to school, things figured to go back to normal.

But they didn’t. The school nurse called. Bella was complaining of stomach pains. She was sent home. This is worth noting because Bella gets stepped on by horses and doesn’t cry. Bella didn’t blink (literally didn’t blink) when she got her ears pierced earlier this year. She once spent the day gallivanting at her grandmother’s house then collapsed in the car when we took her home. We went straight to the doctor and found out she had pneumonia. In other words, when Bella says she’s sick, it’s usually serious. So the next day when she didn’t want to go to school, we kept her home.

But the following day brought more of the same. We forced her to go to school, but that brought another call from the nurse. You see the pattern. Headaches, stomach aches, earaches, sneezes, sniffles. Anything and everything was a reason to go to the nurse. Or, rather, to leave class.

And every morning she had a reason she couldn’t go to school. Tears flowed. We coaxed her encouraged her, yelled at her, and ordered her. She dropped Spanish because it was too hard (which it probably was). She wanted my wife to drive her to school instead of taking the bus. She wanted to change her schedule. Math was too hard. Social studies was too hard. She said the teachers didn’t like her. She spent hours with the guidance counsellor, missing class time.

Bella, this little girl who had always been a success story, a model for what a child with Usher syndrome could accomplish, was falling apart. Worse still, we couldn’t figure out why. In the next post, I’ll take you through our search for a reason.