WEBVTT

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EISERMAN:  I would like to welcome everyone to today's webinar

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entitled 'Genetics and New Developments in the Screening and

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Testing for Healing Loss'.

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I am Will Eiserman, and I am the associate director of the national

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Center for during assessment and management.

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At Utah State University.

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Which is funded by the Maternal and Child Health Bureau.

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To serve as the EHDI National Technical Resource Center.

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And as a part of that, we offer periodic webinars on topics

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relevant to early childhood, hearing and hearing detection

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efforts.

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And today's webinar is just one of those webinars.

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This webinar is being recorded.

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And will be available to stream on our website@infanthearing.org.

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In the next couple of days.

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So, if anything disrupts your attention to today's webinar, know

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that you can access it in the next couple of days on our website.

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And keep that in mind, too.

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In case there are folks that are not attending live today.

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Who you think might benefit from the information that is being

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shared today.

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So, I will turn off my screen share.

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And give our presenter an opportunity to share his screen.

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Our presenter today is Dr.

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Eliot Shearer.

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Who is an assistant professor of otolaryngology, at Harvard Medical

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School.

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Dr.

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Shearer is also practicing pediatric otolaryngologist at

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Boston Children's Hospital.

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Where he cares for hostile -- children with a wide range of ears,

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nose, and throat disorders.

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He has a special interest in the surgical management of pediatric

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ear disorders, including hearing loss.

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Dr.

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Shearer is internationally recognized for his work in

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developing a new genetic testing platform for the diagnosis of

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hearing loss.

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And has written many research articles and several book chapters

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on the subject.

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Dr.

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Shearer also studies ways to improve newborn hearing screening

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tests.

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Using technologies and ways to improve outcomes for children with

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Cochlear Implant.

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So, without further delay, let me introduce Dr.

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Eliot Shearer.

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ELIOT

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ELIOT SHEARER:  Thanks for the

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introduction, Will.

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Thank you so much for having me, I am really honored to be invited to

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speaking to you about today.

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First of all, I would like to thank you all for being here and

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taking time out of your very busy schedule and your very important

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jobs to learn about genetics.

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So, I would like to just say, I have no conflicts of interest.

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I would like to start by changing or reframing how many of us think

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about hearing loss.

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What I mean by this is that, if we think about another diagnosis, or a

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symptom, I mean.

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If you think about someone who comes into the emergency room and

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they have severe chest pain.

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You know, you do not have to be a physician to know that they may be

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having a heart attack.

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Now, when I was a medical student, or an intern, and if I was in an

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emergency room, and if I recommended that immediate leave

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the patient go to the Cath Lab for a cardiac catheterization for the

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symptom of chest pain, which is really just a symptom, I would have

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been laughed out of the room.

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Because we all know that we need to come up with a diagnosis first.

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So, that means doing things like taking a history, physical exam,

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getting vital signs and labs.

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And then doing tests, like an EKG.

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Because you want to make sure that you are diagnosing a heart attack

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before you bring the patient to the operating room.

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And you want to make sure it is not something like acid reflux.

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Which you can treat just with an (Unknown term) , it also has a

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similar symptom.

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I realize as a ...

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and Cochlear Implant surgeon, that I treat patients that have a

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symptom.

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On a daily basis.

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That we do not have a diagnosis for.

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So, what I mean by that is that, we have a symptom of hearing loss

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and this is, you know, a down sloping, mild to severe hearing

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loss you can see here.

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That is symmetric.

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And I take patient like this to the operating room for a Cochlear

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Implant.

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Often, really, we do not have a diagnosis.

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So, I would like to get us to focus on, is the importance of

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diagnosis and reframing the way we are thinking abut hearing loss,

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which is a symptom of an underlying process that is different.

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And this really does affect patient care.

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So, what I mean by that is that, if we diagnose this patient with

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the gene MYH14, this is a stable hearing loss, and it could look

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like this for the rest of your life.

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That reframes the conversation I have with this individual.

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They may decide that they want to use hearing aids instead of

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Cochlear Implant.

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If there hearing is going to be stable for years.

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On the other hand, this same symptom, the same Audiogram, I

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could provide a diagnosis of ACTG1, which is the gene that causes quite

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rapidly progressive hearing loss.

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And again, that may reframe our discussion around hearing aids

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versus Cochlear Implant.

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The same individual with the same hearing loss symptom could also

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have congenital CMV infection.

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And I think everyone on this call today knows that if you are not

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talking to a patient who has a CMV about (Unknown term) when they are

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in infants, then you are not providing the most up-to-date care.

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So, we know that treating children with congenital CMV with (Unknown

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term) can slow or sometime even reversed the hearing loss.

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This individual here could have the symptom of hearing lesson have

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a diagnosis of OTOF, or out of Ferlin hearing loss.

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And there are two clinical trials that are enrolling, or starting to

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enroll individuals for gene therapy.

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So again, the diagnosis totally reframes the discussion I have with

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the family in clinic.

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As opposed to treating a symptom, we need to treat and think about

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the diagnosis.

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So, our improved diagnostic ability has really changed dramatically

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over the past 15 years.

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And it has been brought about by new high-resolution CTs.

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And MRIs.

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Which really show the inner ear anatomy in a way we have not been

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able to before.

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This is an example of a cochlear nerve, or (Unknown term)  shown

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here with the white arrow.

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In many institutions, we are performing CMV testing on a

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universal basis or for individuals who have referred on a newborn

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hearing screening.

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So, this is drastically increase the number of children with CMV

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that we detect.

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There is also tools like electrocochleography.

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We are able to get a better understanding of the physiology of

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the inner ear.

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Using these measures in a way that was not possible 10 years ago.

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And the focus today that I will talk about is genetic testing.

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I will show you how this has changed dramatically over the past

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15 years.

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And it really has altered how we care for individuals who have

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hearing loss.

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Or who are deaf or hard of hearing.

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So, what this means overall is that, in my clinic, where I see the

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majority of children who have hearing loss.

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We are able to come up with diagnoses in most cases.

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So, this is one study from Korea that shows this very nicely.

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So, they had 119 children with severe to profound sensorineural

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hearing loss.

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And they did genetic testing, CMV testing, and high-resolution

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imaging.

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They were able to identify the cause or diagnosis.

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In greater than two thirds of these children.

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This was similar to what I see in my own practice now.

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And this is dramatically different than even 10 years ago.

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When the majority of individuals we did not have a diagnosis for.

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So, what I would like to propose is, we stopped thinking about and

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focusing on the hearing loss.

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And instead, we change to looking at the deaf or hard of hearing

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person.

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And the diagnosis which could be many of really hundreds of

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different things.

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So, they could have CMV -induced inflammatory damage to the (Unknown

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term) , for instance.

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Or the Cochlear nerve hypoplasia.

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Or they could have TMC1 deficiency.

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There is hundreds of different diagnoses that make up or that can

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cause the symptom of hearing loss.

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And that is what leads to reduced hearing.

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What this really provides for us, is personalized care.

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Which is what we all hope to provide to individuals.

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So, as we know, some individuals are -- will choose hearing aids,

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some will go with Cochlear Implant.

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We have auditory brainstem implant for individuals who are unable to

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use Cochlear Implant and willing.

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And then I told you about (Unknown term), and we will talk more about

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gene therapy.

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We also need to alter member that in many cases, none of these

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treatments will be with the family chooses or the best treatment for

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that family.

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For example, the cochlear nerve hypoplasia.

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So, sign language or alternative forms of communication maybe what

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that family chooses.

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My goal in my clinic is to provide the best care for the individual.

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And I believe that by focusing on the diagnosis and not the symptom,

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we are able to come up with the best answer.

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Of course, a team-based approach, like we do at Boston's children

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hospital, is really beneficial in this perspective.

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That is what I -- how I wanted to frame things, before I get started

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with the talk.

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Which is about genetic testing.

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We will talk about sort of a who, what, why, how overview here.

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So, we will talk about what is genetic testing.

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Why should we perform it.

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Who should receive it and how should the clinician order it.

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And what we are going -- while we do this, I will present four

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different patients from my practice that I have seen, that I think

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demonstrate the power and importance of genetic testing and

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genetic evaluation.

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For individuals who are deaf or hard of hearing.

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So, what is genetic testing for hearing loss?

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Well, if you look at all children that have hearing loss, this sums

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up the causes of congenital hearing loss.

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So, about two thirds or 65% is considered genetic.

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About 10% is an anatomic abnormality.

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About 20% is congenital CMV.

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In summer about 5% is due to (Unknown term) toxicity or trauma.

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Usually surrounding birth.

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The genetics of hearing loss, as shown here, if we look at the

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genetic causes.

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About 80%.

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About one third of genetic causes are syndromic, so this means that

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there is other clinical features associated with hearing loss, will

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there is Usher syndrome, which includes hearing loss as well as

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progressive blindness caused by retina -- retina (Unknown term) .

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… (Unknown Name).

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These are just the most common… About 70% is non-syndromic.

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This can be inherited in all different forms.

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The majority is inherited in a recessive fashion.

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Which most typically means that the parents of the child who is

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deaf or hard of hearing do not have hearing loss.

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But, hearing loss is extremely genetically heterogeneous.

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So, what I mean by that is that, there is 124 different known

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hearing loss genes.

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And this is what makes studying hearing loss and testing for

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hearing loss so difficult.

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You know, sometimes I wish that I had studied something like cystic

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fibrosis where there is really only one gene that can cause the

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majority of cases.

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But, at the same time, I think this is what makes studying hearing loss

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so interesting.

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So, if you look at a large group of deaf and hard of hearing

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individuals, in this case, I am showing data from more than 2400.

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There is not one single gene that makes up the majority of cases.

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So, here you can see, TJP2… Is about 20%.

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Stereo sell in, or STRC is the second most common cause of hearing

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loss, but far in a way is the most common cause of mild to moderate

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hearing loss, which I will be talking about later.

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So, because of this extreme genetic heterogeneity, it makes testing

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very difficult.

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Truly, genetic hearing loss is complicated.

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So, what we realized, 14 years ago, is that comprehensive genetic

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testing using massively parallel sequencing is key.

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00:14:54.197 --> 00:14:57.110
So, that is a lot of words.

258
00:14:57.130 --> 00:15:02.110
But, what I mean is, you cannot just test one single gene at a time

259
00:15:02.130 --> 00:15:05.710
for an individual.

260
00:15:05.730 --> 00:15:07.510
You really need to test all of the genes.

261
00:15:07.530 --> 00:15:10.310
So, let me back up and talk a little bit about the history of

262
00:15:10.330 --> 00:15:10.810
this.

263
00:15:10.830 --> 00:15:13.993
So, the human genome project was completed in 2003.

264
00:15:14.013 --> 00:15:17.993
And some people in the call may not remember, this is what

265
00:15:18.013 --> 00:15:21.393
computers used to look like.

266
00:15:21.413 --> 00:15:23.593
These are some of the DNA sequencers that were used to

267
00:15:23.613 --> 00:15:26.793
complete the human genome project.

268
00:15:26.813 --> 00:15:30.793
They used a technology called chain termination sequencing, which was

269
00:15:30.813 --> 00:15:33.593
developed in the 1970s.

270
00:15:33.613 --> 00:15:36.284
And it costed $8000 per million base pairs.

271
00:15:36.304 --> 00:15:42.284
This meant that the human genome the initial sequence cost several

272
00:15:42.304 --> 00:15:45.382
billion dollars to perform the sequencing.

273
00:15:45.402 --> 00:15:48.382
This is what new sequencers look like.

274
00:15:48.402 --> 00:15:53.382
And this is from one company called alumina, that is the

275
00:15:53.402 --> 00:15:56.182
predominant sequencing company.

276
00:15:56.202 --> 00:15:57.582
It uses something called massively parallel sequencing.

277
00:15:57.602 --> 00:16:00.782
And we do not have to get into all of the details, but you can see

278
00:16:00.802 --> 00:16:04.619
essentially sequencing that is performed on a massive scale.

279
00:16:04.639 --> 00:16:05.619
In parallel.

280
00:16:05.639 --> 00:16:08.002
Which means that, you know, at the same time.

281
00:16:08.022 --> 00:16:12.002
This has dramatically reduce the cost of sequencing over the past 15

282
00:16:12.022 --> 00:16:17.992
years since it has been developed.

283
00:16:18.012 --> 00:16:20.155


284
00:16:20.175 --> 00:16:25.155
It is less than a dollar per million base pairs and we can do 80

285
00:16:25.175 --> 00:16:26.355
billion base pairs in 24 hours.

286
00:16:26.375 --> 00:16:28.755
We realized very early that this is exactly the technology that was

287
00:16:28.775 --> 00:16:30.755
needed for something like genetic hearing loss, which is so

288
00:16:30.775 --> 00:16:31.255
complicated.

289
00:16:31.275 --> 00:16:35.255
In my lab now, I have a sequencer that actually fits into the palm of

290
00:16:35.275 --> 00:16:38.655
your hand.

291
00:16:38.675 --> 00:16:39.855
This is the new sequencing technology.

292
00:16:39.875 --> 00:16:42.855
It actually pulls a single molecule DNA through Accor and

293
00:16:42.875 --> 00:16:43.855
sequences at a time.

294
00:16:43.875 --> 00:16:47.855
So, the new developments in sequencing technology are evolving

295
00:16:47.875 --> 00:16:48.855
all the time.

296
00:16:48.875 --> 00:16:51.713
It is really amazing!

297
00:16:51.733 --> 00:16:56.713
But, what this means is that, that the thousand dollar genome is here.

298
00:16:56.733 --> 00:17:00.713
So, for years, people were talking about how things will change.

299
00:17:00.733 --> 00:17:03.674
When it cost $1000 to sequence the genome.

300
00:17:03.694 --> 00:17:06.674
No, we do this essentially on a daily basis.

301
00:17:06.694 --> 00:17:11.674
At Boston's Children's Hospital where we do genome sequencing for

302
00:17:11.694 --> 00:17:13.874
$1000.

303
00:17:13.894 --> 00:17:16.474
You can see in the early 2000's, there was $100 million or more.

304
00:17:16.494 --> 00:17:20.315
So, the fallen cost is dramatic.

305
00:17:20.335 --> 00:17:24.315
So, this is the technology we used to perform copperheads of genetic

306
00:17:24.335 --> 00:17:29.600
testing for hearing loss.

307
00:17:29.620 --> 00:17:30.600
In 2009 and 2010.

308
00:17:30.620 --> 00:17:33.600
This meant for the first time we can sequence all of the hearing

309
00:17:33.620 --> 00:17:37.200
loss genes all at once.

310
00:17:37.220 --> 00:17:43.190
This technology rapidly propagated - you can see within a few years,

311
00:17:43.210 --> 00:17:45.200


312
00:17:45.220 --> 00:17:48.200
there were many different publications.

313
00:17:48.220 --> 00:17:50.200
We published several years after, using this technology for 1119

314
00:17:50.220 --> 00:17:50.700
patients.

315
00:17:50.720 --> 00:17:53.700
Intergroup from Japan came out soon after with 1120 patients, just

316
00:17:53.720 --> 00:17:55.700
to show they could beat us.

317
00:17:55.720 --> 00:17:57.955
-- And a group.

318
00:17:57.975 --> 00:18:01.955
What this means is that, this technology is is often used in

319
00:18:01.975 --> 00:18:05.422
hundreds of studies and thousands of patients.

320
00:18:05.442 --> 00:18:08.422
There is now several different companies around the country that

321
00:18:08.442 --> 00:18:14.918
perform this testing.

322
00:18:14.938 --> 00:18:16.918
Or a similar version of this testing.

323
00:18:16.938 --> 00:18:19.318
This is the testing I helped develop at the University of Iowa,

324
00:18:19.338 --> 00:18:23.318
but you can see there are other companies here.

325
00:18:23.338 --> 00:18:27.318
I do not have any financial relationship with any of them.

326
00:18:27.338 --> 00:18:29.718
But, this company is a genetic testing for hearing loss has now

327
00:18:29.738 --> 00:18:31.918
become the standard of care for evaluation of child hearing loss.

328
00:18:31.938 --> 00:18:33.918
All of these different tests essentially do the same thing.

329
00:18:33.938 --> 00:18:38.453
So, they use these new sequencing techniques.

330
00:18:38.473 --> 00:18:42.453
Just to give -- sequence all of the non-it syndrome a hearing last

331
00:18:42.473 --> 00:18:45.453
income as well as many of the syndromic hearing Lester jeans,

332
00:18:45.473 --> 00:18:46.453
like (Unknown Name) syndrome.

333
00:18:46.473 --> 00:18:50.655
Because we are better able to test for them at the same time.

334
00:18:50.675 --> 00:18:55.021
We are identifying the syndromes earlier and earlier.

335
00:18:55.041 --> 00:18:59.275
So, why do we perform genetic testing for hearing loss?

336
00:18:59.295 --> 00:19:02.275
Well, really, the easiest answer is that it is the single most

337
00:19:02.295 --> 00:19:05.075
effective test.

338
00:19:05.095 --> 00:19:11.065
So, if you look across all studies, and this is relatively even and it

339
00:19:11.085 --> 00:19:13.075


340
00:19:13.095 --> 00:19:19.065
has been similar for the past year or so, if you order a test for an

341
00:19:19.085 --> 00:19:20.075


342
00:19:20.095 --> 00:19:24.075
individual and hearing loss, the diagnostic yield, or also

343
00:19:24.095 --> 00:19:26.075
diagnostic rate, is about 40%.

344
00:19:26.095 --> 00:19:28.675
So, that means that in 40% of people, we come up with a

345
00:19:28.695 --> 00:19:31.410
diagnosis.

346
00:19:31.430 --> 00:19:37.410
If -- I was raised some sites later, which showed that this is higher.

347
00:19:37.430 --> 00:19:40.410
So, it is more like 50 to 60%.

348
00:19:40.430 --> 00:19:44.410
But, if you just ordered a CT scan or an MRI, the diagnostic rate

349
00:19:44.430 --> 00:19:46.410
would be lower, so close to 30%.

350
00:19:46.430 --> 00:19:51.410
Even when I started training, we would do other testing.

351
00:19:51.430 --> 00:19:53.603
Like, we would get ultrasounds.

352
00:19:53.623 --> 00:19:54.803
And blood tests.

353
00:19:54.823 --> 00:19:58.803
And these tests do not really have very much of the diagnostic yield,

354
00:19:58.823 --> 00:20:02.003
is very low.

355
00:20:02.023 --> 00:20:05.003
The other important reason to do genetic testing is because it

356
00:20:05.023 --> 00:20:08.373
provides really important information for families.

357
00:20:08.393 --> 00:20:11.373
It provides prognostic information, so whether the during loss will

358
00:20:11.393 --> 00:20:15.642
stay the same or worse over time.

359
00:20:15.662 --> 00:20:16.642
-- The hearing loss.

360
00:20:16.662 --> 00:20:20.642
It also provides information on recurrent risk for patients and

361
00:20:20.662 --> 00:20:21.142
families.

362
00:20:21.162 --> 00:20:24.142
So, if they would have another child, what are the chances they

363
00:20:24.162 --> 00:20:25.142
would be affected?

364
00:20:25.162 --> 00:20:29.142
Or will their children -- when their children going to have

365
00:20:29.162 --> 00:20:33.142
children, but are the chances that -- that they will have hearing

366
00:20:33.162 --> 00:20:34.201
loss?

367
00:20:34.221 --> 00:20:39.652
… We are finding really does comprise about 20% of diagnoses.

368
00:20:39.672 --> 00:20:45.652
And what I think maybe one of the most important income is not the

369
00:20:45.672 --> 00:20:49.652
most important thing, is what I find for my family is, it really

370
00:20:49.672 --> 00:20:53.252
empowers the patients and families.

371
00:20:53.272 --> 00:20:56.252
But what I mean by this is, instead of just having a symptom, like I

372
00:20:56.272 --> 00:20:58.781
talked about, it provides a diagnosis.

373
00:20:58.801 --> 00:21:01.781
So, for instance, this is the stereo cell and gene mutation

374
00:21:01.801 --> 00:21:04.806
hearing loss Facebook group.

375
00:21:04.826 --> 00:21:07.902
And one of my patient's family started this.

376
00:21:07.922 --> 00:21:14.550
And they have many members of this group now.

377
00:21:14.570 --> 00:21:17.150
It provides a sense of empowerment for the family so they can meet

378
00:21:17.170 --> 00:21:21.680
other members of their community and they can share their diagnosis.

379
00:21:21.700 --> 00:21:26.680
So, I would like to talk about the first patient.

380
00:21:26.700 --> 00:21:30.647
So, this individual is a seven month old.

381
00:21:30.667 --> 00:21:33.277
It was referred on the newborn hearing screening bilaterally.

382
00:21:33.297 --> 00:21:38.277
And you can see an audio that we have here where it is profound

383
00:21:38.297 --> 00:21:41.677
hearing loss bilaterally.

384
00:21:41.697 --> 00:21:43.477
And the family was really on top of things.

385
00:21:43.497 --> 00:21:45.797
You know, they had hearing aids since three-month-old.

386
00:21:45.817 --> 00:21:49.520
And by seven months, it was meeting developmental milestones.

387
00:21:49.540 --> 00:21:54.520
You can imagine the questions the parents would be asking.

388
00:21:54.540 --> 00:21:58.520
What is the cause of the hearing loss?

389
00:21:58.540 --> 00:21:59.320
What is the prognosis?

390
00:21:59.340 --> 00:22:01.120
What the recurrence risk is.

391
00:22:01.140 --> 00:22:02.120
We did genetic testing.

392
00:22:02.140 --> 00:22:07.038
It came up with two pathogenic variations in the genes CDH23.

393
00:22:07.058 --> 00:22:11.413
This is the most common cause of Usher syndrome type I.

394
00:22:11.433 --> 00:22:16.413
This is severe to profound hearing loss with vestibular function,

395
00:22:16.433 --> 00:22:19.092
which can lead to delayed motor milestones.

396
00:22:19.112 --> 00:22:25.404
As well as progressive vision loss due to retinitis pigmentosa.

397
00:22:25.424 --> 00:22:29.404
So, these are some of the most difficult days that I have in

398
00:22:29.424 --> 00:22:35.394
clinic - providing this result back to a family.

399
00:22:35.414 --> 00:22:37.522


400
00:22:37.542 --> 00:22:43.522
It is really a unique position, I have quite routinely where I am

401
00:22:43.542 --> 00:22:49.512
providing a diagnosis of a vision problem before it even occurs.

402
00:22:49.532 --> 00:22:52.021


403
00:22:52.041 --> 00:22:55.021
Because we are often ordering genetic testing, now we are often

404
00:22:55.041 --> 00:22:58.315
the providers who give this result back.

405
00:22:58.335 --> 00:23:04.305
I will tell you that having this diagnosis of a dual sensory

406
00:23:04.325 --> 00:23:06.315


407
00:23:06.335 --> 00:23:11.315
impairment really changes the discussion for possible treatment

408
00:23:11.335 --> 00:23:12.315
options.

409
00:23:12.335 --> 00:23:14.315
It reframes our discussion talking about Cochlear Implant, for

410
00:23:14.335 --> 00:23:16.315
instance.

411
00:23:16.335 --> 00:23:18.315
Although providing this result back to families can be very

412
00:23:18.335 --> 00:23:22.315
devastating, universally, when I talk to families, after they have

413
00:23:22.335 --> 00:23:28.305
had some time they have been so thankful to have the diagnosis.

414
00:23:28.325 --> 00:23:29.309


415
00:23:29.329 --> 00:23:33.309
Just because they're able to do things like teach a child braille

416
00:23:33.329 --> 00:23:36.309
before they start to lose vision and they can start to take vitamins,

417
00:23:36.329 --> 00:23:42.309
like vitamin A, and wear sunglasses to delay the onset of

418
00:23:42.329 --> 00:23:45.309
retinitis pigmentosa… Although this diagnosis is very hard to give, it

419
00:23:45.329 --> 00:23:51.299
is very important for us.

420
00:23:51.319 --> 00:23:54.380


421
00:23:54.400 --> 00:23:56.951
… It is 40%.

422
00:23:56.971 --> 00:23:59.951
And you know, sometimes I am thinking kind of negatively about

423
00:23:59.971 --> 00:24:02.551
that too.

424
00:24:02.571 --> 00:24:04.951
I was talking to one of my colleagues who is a neurologist.

425
00:24:04.971 --> 00:24:09.951
And I said, "my diagnostic is so low, it is 40%." And she said,

426
00:24:09.971 --> 00:24:11.951
"what are you talking about?

427
00:24:11.971 --> 00:24:12.951
That is great!

428
00:24:12.971 --> 00:24:13.451
"

429
00:24:13.471 --> 00:24:17.451
So, we started looking into it, and these are genetic disorders,

430
00:24:17.471 --> 00:24:20.451
neurological disorders, that they routinely order genetic testing

431
00:24:20.471 --> 00:24:20.951
for.

432
00:24:20.971 --> 00:24:24.990
So, it is very common now to obtain genetic testing for autism.

433
00:24:25.010 --> 00:24:28.919
The diagnostic rate for that is about 17%.

434
00:24:28.939 --> 00:24:31.919
Almost every child now with epilepsy undergoes genetic testing

435
00:24:31.939 --> 00:24:33.719
because there are specific treatments that are available for

436
00:24:33.739 --> 00:24:36.329
them.

437
00:24:36.349 --> 00:24:39.263
Even then, the diagnostic rate is about 24%.

438
00:24:39.283 --> 00:24:43.263
And then children with intellectual disability routinely undergo

439
00:24:43.283 --> 00:24:46.642
genetic testing and that diagnostic rate is 28%.

440
00:24:46.662 --> 00:24:50.642
And now in the NICU, it is becoming more and more common to

441
00:24:50.662 --> 00:24:54.511
obtain rapid genetic testing.

442
00:24:54.531 --> 00:24:55.511
And rapid genome sequencing.

443
00:24:55.531 --> 00:24:58.513
To provide a diagnosis.

444
00:24:58.533 --> 00:25:01.513
And this is hugely expensive because they try to get the results

445
00:25:01.533 --> 00:25:05.113
back within 24 to 48 hrs.

446
00:25:05.133 --> 00:25:11.103
In the diagnostic rate there is about 36%… What this means is that,

447
00:25:11.123 --> 00:25:13.113


448
00:25:13.133 --> 00:25:18.113
as a provider, taking care of individuals who are deaf or hard of

449
00:25:18.133 --> 00:25:20.413
hearing, you all are geneticists.

450
00:25:20.433 --> 00:25:25.413
It is important for all of you to understand the genetics of hearing

451
00:25:25.433 --> 00:25:28.657
loss as well.

452
00:25:28.677 --> 00:25:30.657
So, we will talk about another patient.

453
00:25:30.677 --> 00:25:35.657
So, this is an 18-year-old that I saw who had his congenital hearing

454
00:25:35.677 --> 00:25:38.457
loss.

455
00:25:38.477 --> 00:25:41.057
And it was, as you can see here, it was mild to moderate.

456
00:25:41.077 --> 00:25:43.289
With a little bit of a mixed component.

457
00:25:43.309 --> 00:25:48.289
And this patient had eustachian tube dysfunction, had a bunch of

458
00:25:48.309 --> 00:25:50.889
tubes placed.

459
00:25:50.909 --> 00:25:53.089
So, her whole life, she was dealing with tubes, and straining

460
00:25:53.109 --> 00:25:56.144
ears.

461
00:25:56.164 --> 00:26:00.144
No one had brought up her underlying hearing loss that she

462
00:26:00.164 --> 00:26:03.144
had been struggling with.

463
00:26:03.164 --> 00:26:06.288
It was attributed to her tubes and her eustachian tube dysfunction.

464
00:26:06.308 --> 00:26:12.512
She wore hearing aids, but not all of the time.

465
00:26:12.532 --> 00:26:14.512
She also struggles with ADHD.

466
00:26:14.532 --> 00:26:17.512
So, because we have a research study with children's, we were able

467
00:26:17.532 --> 00:26:18.512
to enroll her in this.

468
00:26:18.532 --> 00:26:21.512
And we perform genetic evaluation because she really just wanted to

469
00:26:21.532 --> 00:26:24.512
know what the cause of hearing loss was and what the prognosis would

470
00:26:24.532 --> 00:26:25.012
be.

471
00:26:25.032 --> 00:26:28.012
So, she is 18, she would want to know whether it would stay the same

472
00:26:28.032 --> 00:26:32.012
or get worse over time.

473
00:26:32.032 --> 00:26:36.223
What we found was a pathogenic variation in the gene FGRF3.

474
00:26:36.243 --> 00:26:40.223
At the age of 18 years old, we were able to give her a diagnosis

475
00:26:40.243 --> 00:26:43.823
of Muenke Syndrome.

476
00:26:43.843 --> 00:26:49.813
This is a syndrome that is associated with cranial (Unknown

477
00:26:49.833 --> 00:27:11.823


478
00:27:11.843 --> 00:27:17.813
term), so abnormal, early fusion of the skull and hearing loss, as well

479
00:27:17.833 --> 00:27:34.823


480
00:27:34.843 --> 00:27:39.074
as ADHD.

481
00:27:39.094 --> 00:27:41.474
So, finally, at 18 years of age, she was provided with the

482
00:27:41.494 --> 00:27:45.521
diagnosis.

483
00:27:45.541 --> 00:27:48.521
This was hugely impactful for her because the next time that I saw

484
00:27:48.541 --> 00:27:52.521
her back, it was almost like she had accepted her diagnosis more and

485
00:27:52.541 --> 00:27:56.437
she was wearing her hearing aids.

486
00:27:56.457 --> 00:27:59.437
Dylan Chan, who was at the University of San Francisco, has

487
00:27:59.457 --> 00:28:02.437
shown that providing a diagnosis to children increases their use of

488
00:28:02.457 --> 00:28:05.037
hearing aids.

489
00:28:05.057 --> 00:28:09.037
For this reason, I think, it is important that we pursue this.

490
00:28:09.057 --> 00:28:14.037
So, the other point I will make about this patient is that, for a

491
00:28:14.057 --> 00:28:17.037
lot of these syndromes, there is something called a syndromic

492
00:28:17.057 --> 00:28:17.537
spectrum.

493
00:28:17.557 --> 00:28:21.537
So, what I mean by that is that, they first diagnosed, or first came

494
00:28:21.557 --> 00:28:26.537
up with these syndromes years ago, they probably looked at the most

495
00:28:26.557 --> 00:28:29.337
severely affected.

496
00:28:29.357 --> 00:28:31.737
But, what we are finding, is with we perform testing of more

497
00:28:31.757 --> 00:28:35.737
individuals who are able to find that there is someone who has more

498
00:28:35.757 --> 00:28:38.737
of a mild phenotype, or a more mild, clinical features.

499
00:28:38.757 --> 00:28:40.704
This was very important for this individual.

500
00:28:40.724 --> 00:28:44.704
Even though this is not someone that you would typically think, "we

501
00:28:44.724 --> 00:28:48.124
should do genetic testing for." I am glad we do.

502
00:28:48.144 --> 00:28:50.124
More about the prognosis and management.

503
00:28:50.144 --> 00:28:54.124
I just wanted to show you two different genes that have a very

504
00:28:54.144 --> 00:28:56.124
different prognosis.

505
00:28:56.144 --> 00:29:00.124
So, these are combined audiograms of different individuals with two

506
00:29:00.144 --> 00:29:03.408
forms of hearing loss.

507
00:29:03.428 --> 00:29:03.908
Techda (?

508
00:29:03.928 --> 00:29:10.005
) And KC and Q4.

509
00:29:10.025 --> 00:29:14.005
What you can see over time, is the hearing loss for it (Unknown Name)

510
00:29:14.025 --> 00:29:15.868
is relatively stable.

511
00:29:15.888 --> 00:29:21.858
Whereas for KC and Q4, there is about a ten bold drop per decade.

512
00:29:21.878 --> 00:29:23.851


513
00:29:23.871 --> 00:29:25.851
That we can see here.

514
00:29:25.871 --> 00:29:28.851
This really reframes how we think about Cochlear Implant versus

515
00:29:28.871 --> 00:29:34.237
hearing aids.

516
00:29:34.257 --> 00:29:38.237
On a day-to-day basis, if I have a genetic diagnosis, it changes the…

517
00:29:38.257 --> 00:29:43.237
So, if I know the child has a stable form of hearing loss, we may

518
00:29:43.257 --> 00:29:47.463
be able to push a visit out to one year.

519
00:29:47.483 --> 00:29:50.867
Whereas otherwise, we may see the back every 4 to 6 months.

520
00:29:50.887 --> 00:29:55.113
It does change my clinical practice on a day-to-day basis.

521
00:29:55.133 --> 00:29:58.455
Another reason why these consensus guidelines.

522
00:29:58.475 --> 00:30:02.455
There has been a couple of different guidelines from the

523
00:30:02.475 --> 00:30:05.583
international (Unknown term) otolaryngology group.

524
00:30:05.603 --> 00:30:08.583
And people say that genetic testing should be a part of the

525
00:30:08.603 --> 00:30:13.779
evaluation of children of hearing loss.

526
00:30:13.799 --> 00:30:17.318
I also want to talk about Cochlear Implant outcomes.

527
00:30:17.338 --> 00:30:23.308
So, if you look at any group of Cochlear Implant patients, you may

528
00:30:23.328 --> 00:30:24.318


529
00:30:24.338 --> 00:30:27.318
see something that looks like this.

530
00:30:27.338 --> 00:30:29.628
So, post operative word recognitions.

531
00:30:29.648 --> 00:30:31.628
Are on average, something like this.

532
00:30:31.648 --> 00:30:34.601
So, 70% for one test, Caspian Sea.

533
00:30:34.621 --> 00:30:37.706
60% for another text.

534
00:30:37.726 --> 00:30:42.706
What is underlying this data, is actually a huge variability and

535
00:30:42.726 --> 00:30:45.106
outcomes.

536
00:30:45.126 --> 00:30:47.506
So, there is some individuals who have a Cochlear Implant and they

537
00:30:47.526 --> 00:30:48.506
get 0% word recognition.

538
00:30:48.526 --> 00:30:51.626
And others may get 100%.

539
00:30:51.646 --> 00:30:55.626
I really find this to be quite unacceptable.

540
00:30:55.646 --> 00:31:01.537
Because I would like to be able to cancel my families.

541
00:31:01.557 --> 00:31:03.881
The children that I see.

542
00:31:03.901 --> 00:31:07.881
Effectively, as far as how well a Cochlear Implant is going to work.

543
00:31:07.901 --> 00:31:10.854
So, that is a big part of my research.

544
00:31:10.874 --> 00:31:12.854
Trying to understand these Cochlear Implant outcomes.

545
00:31:12.874 --> 00:31:14.497
So, we know that these outcomes are variable.

546
00:31:14.517 --> 00:31:19.497
And can we improve outcomes with a better understanding of genetics?

547
00:31:19.517 --> 00:31:22.304
Is the question.

548
00:31:22.324 --> 00:31:25.304
So, Cochlear Implant outcomes, it is clearly complicated.

549
00:31:25.324 --> 00:31:29.304
So, we know there are things like the environment, so, socioeconomic

550
00:31:29.324 --> 00:31:31.704
status.

551
00:31:31.724 --> 00:31:32.904
Time without hearing.

552
00:31:32.924 --> 00:31:34.104
The social interactions.

553
00:31:34.124 --> 00:31:35.904
These clearly play a role in Cochlear Implant outcomes.

554
00:31:35.924 --> 00:31:38.904
And then there is clinical variables, so things like what

555
00:31:38.924 --> 00:31:44.894
device is used, what surgeon… Activation in training afterwards.

556
00:31:44.914 --> 00:31:46.904


557
00:31:46.924 --> 00:31:49.904
I would propose that, genes are likely involved, too.

558
00:31:49.924 --> 00:31:55.904
So, genes that could affect the sensory pathways as well as the

559
00:31:55.924 --> 00:31:58.704
central pathway.

560
00:31:58.724 --> 00:31:59.904
So, the brain.

561
00:31:59.924 --> 00:32:02.904
And I really do think that a better understanding of Cochlear

562
00:32:02.924 --> 00:32:07.904
Implant genetics could allow us identification of poor performers

563
00:32:07.924 --> 00:32:09.904
preoperatively.

564
00:32:09.924 --> 00:32:13.904
So, what I mean by this is that, if we think that someone is at a

565
00:32:13.924 --> 00:32:16.904
higher risk of not doing as well with the Cochlear Implant, we can

566
00:32:16.924 --> 00:32:20.014
focus the activation and training and follow-up.

567
00:32:20.034 --> 00:32:22.014
For those at risk patients.

568
00:32:22.034 --> 00:32:25.014
And then really importantly, I would like to be able to counsel my

569
00:32:25.034 --> 00:32:27.104
families and patients effectively.

570
00:32:27.124 --> 00:32:32.081
With how I expect they are going to be doing after surgery.

571
00:32:32.101 --> 00:32:35.081
And then ultimately, this could also pave the way to position

572
00:32:35.101 --> 00:32:38.369
tailor Cochlear Implant.

573
00:32:38.389 --> 00:32:44.359
So, to get into more detail about this, if you think about the

574
00:32:44.379 --> 00:32:47.369


575
00:32:47.389 --> 00:32:49.569
auditory pathway as the schematic year, you have the hairstyle, you

576
00:32:49.589 --> 00:32:51.369
have the nerve, and then you have the brainstem.

577
00:32:51.389 --> 00:32:54.369
The cochlear and plant electrode bypasses the hairstyle and it

578
00:32:54.389 --> 00:32:56.969
simulates the nerve.

579
00:32:56.989 --> 00:32:59.969
You would -- our hypothesis would be that, individuals who have a

580
00:32:59.989 --> 00:33:03.969
damaging genetic mutation or variant affecting the spiral

581
00:33:03.989 --> 00:33:07.871
ganglion will have a significantly worse Cochlear Implant outcomes.

582
00:33:07.891 --> 00:33:12.871
What I mean by that, is that it has actually been known for a while now

583
00:33:12.891 --> 00:33:16.871
that if you have sensory dysfunction, so if you have a

584
00:33:16.891 --> 00:33:20.871
genetic variant that affects the hair cells specifically, like GGP 2

585
00:33:20.891 --> 00:33:23.071
for instance, this are some of the best performers with copper

586
00:33:23.091 --> 00:33:29.061
implants.

587
00:33:29.081 --> 00:33:31.782


588
00:33:31.802 --> 00:33:35.782
Whereas we propose if you have a neural dysfunction due to genetics,

589
00:33:35.802 --> 00:33:38.582
if your nerve is not working as well, you may have a poor outcome.

590
00:33:38.602 --> 00:33:40.782
Well, there is close to 100 different genes that affect the

591
00:33:40.802 --> 00:33:46.772
organ (Unknown term) , or the synapse.

592
00:33:46.792 --> 00:33:51.104


593
00:33:51.124 --> 00:33:54.104
And there are fewer genes to affect the nondirected.

594
00:33:54.124 --> 00:33:57.104
Elected this a few years ago and what you can see is, when we looked

595
00:33:57.124 --> 00:33:59.704
at the Z score average of the individuals who had a genetic cause

596
00:33:59.724 --> 00:34:02.304
that was neural or a sensory cause of hearing loss that was genetic,

597
00:34:02.324 --> 00:34:05.304
versus things like otosclerosis and sudden hearing loss, the

598
00:34:05.324 --> 00:34:09.304
individuals that had a neural genetic cause of hearing loss

599
00:34:09.324 --> 00:34:15.294
performed worse overall than those that had a sensory genetic form of

600
00:34:15.314 --> 00:34:17.304


601
00:34:17.324 --> 00:34:18.304
hearing loss.

602
00:34:18.324 --> 00:34:21.304
I do think genetic variants that affect the auditory nerve are

603
00:34:21.324 --> 00:34:22.504
associated with worse Cochlear Implant outcomes.

604
00:34:22.524 --> 00:34:27.420
There is a lot more work that needs to be done in this area, too.

605
00:34:27.440 --> 00:34:33.420
To do the study again with a greater number of patients.

606
00:34:33.440 --> 00:34:35.420
And this was adults.

607
00:34:35.440 --> 00:34:38.420
So, I want to talk about another patient.

608
00:34:38.440 --> 00:34:41.420
So, this is the patient you came to see me for Cochlear Implant

609
00:34:41.440 --> 00:34:44.220
evaluation.

610
00:34:44.240 --> 00:34:45.620
This is what the Audiogram looks like.

611
00:34:45.640 --> 00:34:48.220
So, it is sharply down sloping.

612
00:34:48.240 --> 00:34:49.620
Normal to severe to profound hearing loss.

613
00:34:49.640 --> 00:34:53.620
This patient's word recognition scores were decreasing

614
00:34:53.640 --> 00:34:55.620
significantly over time.

615
00:34:55.640 --> 00:34:58.020
They wanted to know what the cause of the hearing loss was.

616
00:34:58.040 --> 00:35:01.020
And what -- whether a cochlear implant was the right treatment or

617
00:35:01.040 --> 00:35:03.984
whether they wanted to continue with hearing aids.

618
00:35:04.004 --> 00:35:07.984
We did genetic testing, we identified pathogenic variance in

619
00:35:08.004 --> 00:35:10.821
the gene TMPRSS3.

620
00:35:10.841 --> 00:35:13.160
This is a cause of non-syndromic hearing loss.

621
00:35:13.180 --> 00:35:17.160
It is very controversial, but some groups have shown that individuals

622
00:35:17.180 --> 00:35:22.160
with this form of hearing loss have worse outcomes after two --

623
00:35:22.180 --> 00:35:24.960
Cochlear Implant.

624
00:35:24.980 --> 00:35:27.960
This is still - there is conflicting data, one way or

625
00:35:27.980 --> 00:35:28.960
another on it.

626
00:35:28.980 --> 00:35:30.960
But, we had a long discussion about this.

627
00:35:30.980 --> 00:35:33.960
Because I want to make sure that individuals are adequately

628
00:35:33.980 --> 00:35:35.560
counseled prior to cochlear implantation based on their

629
00:35:35.580 --> 00:35:38.982
diagnosis.

630
00:35:39.002 --> 00:35:43.982
I should point out, though, that I am not saying that individuals with

631
00:35:44.002 --> 00:35:49.982
TMPRSS3 hearing loss or other genetic forms of hearing loss that

632
00:35:50.002 --> 00:35:55.982
may be associated with more poor Cochlear Implant outcomes should

633
00:35:56.002 --> 00:35:57.782
not have a Cochlear Implant, because Cochlear Implant, for

634
00:35:57.802 --> 00:35:59.782
individuals who want that, are the most effective available treatment

635
00:35:59.802 --> 00:36:02.982
for severe to profound hearing loss.

636
00:36:03.002 --> 00:36:07.982
And so, my point overall is that, we should work towards better

637
00:36:08.002 --> 00:36:11.382
counseling based on the diagnosis.

638
00:36:11.402 --> 00:36:15.382
Because after all, some individuals do very well with the Cochlear

639
00:36:15.402 --> 00:36:15.882
Implant.

640
00:36:15.902 --> 00:36:18.882
And TMPRSS3 hearing loss, for instance.

641
00:36:18.902 --> 00:36:23.882
But you would like to be able to counsel effectively.

642
00:36:23.902 --> 00:36:27.971
So, another reason why, is gene hearing for their loss.

643
00:36:27.991 --> 00:36:31.312
-- Gene therapy for hearing loss.

644
00:36:31.332 --> 00:36:34.355
This is a rapidly evolving area right now.

645
00:36:34.375 --> 00:36:36.990
I will talk just for a moment about it today.

646
00:36:37.010 --> 00:36:43.082
And maybe in the future we will talk more about it.

647
00:36:43.102 --> 00:36:46.082
I have very mixed feelings about moving forward with this.

648
00:36:46.102 --> 00:36:49.082
Gene therapy for hearing loss.

649
00:36:49.102 --> 00:36:53.727
And we can get into that another date.

650
00:36:53.747 --> 00:36:56.727
But, there are different methods for liking their therapy for

651
00:36:56.747 --> 00:36:57.727
hearing loss.

652
00:36:57.747 --> 00:37:00.727
So, there is replacing a gene, or suppressing the gene, or editing

653
00:37:00.747 --> 00:37:03.527
the gene.

654
00:37:03.547 --> 00:37:06.527
And there is also the considerations like the ethics of

655
00:37:06.547 --> 00:37:08.527
doing gene therapy for hearing loss.

656
00:37:08.547 --> 00:37:12.518
Just to begin with.

657
00:37:12.538 --> 00:37:16.518
We do not know how well it would work, the virus can have systemic

658
00:37:16.538 --> 00:37:17.518
effects on the whole body.

659
00:37:17.538 --> 00:37:19.518
And how safe it is.

660
00:37:19.538 --> 00:37:23.518
But, the point is that, any genetic therapy requires an accurate,

661
00:37:23.538 --> 00:37:25.499
genetic, diagnosis first.

662
00:37:25.519 --> 00:37:29.499
So, you cannot even think about gene therapy unless you have an

663
00:37:29.519 --> 00:37:33.698
accurate, genetic, diagnosis.

664
00:37:33.718 --> 00:37:38.698
I will say, whether you like it or not, gene therapy for hearing loss

665
00:37:38.718 --> 00:37:41.698
here.

666
00:37:41.718 --> 00:37:44.698
So, I think most of you have heard that there is two companies now who

667
00:37:44.718 --> 00:37:46.698
are opening up clinical trials.

668
00:37:46.718 --> 00:37:49.098
For gene therapy for hearing loss.

669
00:37:49.118 --> 00:37:51.298
I have no financial relationship with these or either of them.

670
00:37:51.318 --> 00:37:57.288
But, when company isAkouous and the other is Decibel, and the error …

671
00:37:57.308 --> 00:38:00.298


672
00:38:00.318 --> 00:38:06.288
For OTOF… Genetic hearing loss.

673
00:38:06.308 --> 00:38:09.658


674
00:38:09.678 --> 00:38:12.658
You can see from their website, the next targets are things like

675
00:38:12.678 --> 00:38:13.658
GGP 2.

676
00:38:13.678 --> 00:38:16.258
As I told you, it is the most common, genetic form of hearing

677
00:38:16.278 --> 00:38:16.758
loss.

678
00:38:16.778 --> 00:38:20.404
So, this is happening now.

679
00:38:20.424 --> 00:38:24.404
As providers who care for children that have hearing loss, this is

680
00:38:24.424 --> 00:38:28.443
something that you should all at least know something about.

681
00:38:28.463 --> 00:38:32.443
So, the less patient I want to talk about is this patient.

682
00:38:32.463 --> 00:38:34.568
So, this is their Audiogram.

683
00:38:34.588 --> 00:38:37.568
They have a mild to moderate symmetric sensorineural hearing

684
00:38:37.588 --> 00:38:38.068
loss.

685
00:38:38.088 --> 00:38:42.068
Again, this is maybe someone that you would not necessarily

686
00:38:42.088 --> 00:38:46.068
automatically say, "we have to get genetic testing for." But, this is

687
00:38:46.088 --> 00:38:49.157
a seven year old who did not pass their newborn hearing screening.

688
00:38:49.177 --> 00:38:50.157
Otherwise healthy.

689
00:38:50.177 --> 00:38:53.388
And is doing great with hearing aids.

690
00:38:53.408 --> 00:38:59.303
But, the family wanted to know about the prognosis primarily.

691
00:38:59.323 --> 00:39:01.703
They are also very active in wanting to be involved in the

692
00:39:01.723 --> 00:39:02.478
childcare.

693
00:39:02.498 --> 00:39:08.468
We were able to provide them with a diagnosis of STRC hearing loss

694
00:39:08.488 --> 00:39:09.478


695
00:39:09.498 --> 00:39:13.270
because of deletion of the stereo sound the gene.

696
00:39:13.290 --> 00:39:17.270
I told you, this is the second most common cause of genetic

697
00:39:17.290 --> 00:39:20.270
hearing loss overall.

698
00:39:20.290 --> 00:39:22.870
And by far, the most common cause of mild to moderate hearing loss.

699
00:39:22.890 --> 00:39:25.070
Now that we are testing these individuals, we are finding this

700
00:39:25.090 --> 00:39:28.070
more and more frequently.

701
00:39:28.090 --> 00:39:31.070
That there is a long background of this gene, but it is very hard to

702
00:39:31.090 --> 00:39:31.570
sequence.

703
00:39:31.590 --> 00:39:35.570
So, until these new technologies came along, we were not able to

704
00:39:35.590 --> 00:39:38.970
test for it very well.

705
00:39:38.990 --> 00:39:41.370
Now, we are finding it is much more common then we realized

706
00:39:41.390 --> 00:39:41.870
before.

707
00:39:41.890 --> 00:39:44.870
But, the first thing this family wanted to know after we gave them a

708
00:39:44.890 --> 00:39:47.870
diagnosis, this diagnosis, is whether there was a gene therapy

709
00:39:47.890 --> 00:39:48.370
available.

710
00:39:48.390 --> 00:39:53.370
You may be looking at this hearing test and say to yourself, "they

711
00:39:53.390 --> 00:39:56.370
were hearing aids, why would they want gene therapy?

712
00:39:56.390 --> 00:39:57.370
"

713
00:39:57.390 --> 00:40:01.370
Again, this is where I would argue that we need to care for each

714
00:40:01.390 --> 00:40:04.157
family as they would like to be cared for individually.

715
00:40:04.177 --> 00:40:10.157
So, hearing loss in children, we show that gene therapy for STOC

716
00:40:10.177 --> 00:40:13.157
hearing loss is effective in mice.

717
00:40:13.177 --> 00:40:15.557
So, this is showing electron microscopy of the hair cells of a

718
00:40:15.577 --> 00:40:19.757
mouse.

719
00:40:19.777 --> 00:40:22.757
You can see on the left, the hair cells that were treated.

720
00:40:22.777 --> 00:40:27.757
On the right, the hair cells that were, or sorry, the hairs on the

721
00:40:27.777 --> 00:40:29.757
left rehearsals that were untreated.

722
00:40:29.777 --> 00:40:31.157
On the right, herself that were treated.

723
00:40:31.177 --> 00:40:34.191
You can see that they are stating a nice, straight rows again.

724
00:40:34.211 --> 00:40:38.191
This family, every time I see them, ask about gene therapy for hearing

725
00:40:38.211 --> 00:40:40.991
loss.

726
00:40:41.011 --> 00:40:45.991
As I told you, the companies have them on the horizon.

727
00:40:46.011 --> 00:40:50.996
The next two years the landscapes will be changing, I think.

728
00:40:51.016 --> 00:40:56.996
So, who should we be performing genetic testing for hearing loss

729
00:40:57.016 --> 00:40:57.996
for?

730
00:40:58.016 --> 00:40:59.396
The diagnostic rate varies by clinical characteristics.

731
00:40:59.416 --> 00:41:01.396
I told you overall, the diagnostic rate was about 40%.

732
00:41:01.416 --> 00:41:04.400
This is data from a few years ago now.

733
00:41:04.420 --> 00:41:07.400
But, if there is a family history of hearing loss, the diagnostic

734
00:41:07.420 --> 00:41:10.600
rate can be higher.

735
00:41:10.620 --> 00:41:13.000
If the age of onset is earlier, the diagnostic rate is higher.

736
00:41:13.020 --> 00:41:17.000
And if it is a symmetric hearing loss, the diagnostic rate is higher

737
00:41:17.020 --> 00:41:20.000
as well.

738
00:41:20.020 --> 00:41:23.000
So, when I see a child that has congenital profound sensorineural

739
00:41:23.020 --> 00:41:27.000
hearing loss, in a normal -- and normal, physical exam, I tell them

740
00:41:27.020 --> 00:41:29.400
they have about a 60% chance of having a diagnosis from genetic

741
00:41:29.420 --> 00:41:33.044
testing.

742
00:41:33.064 --> 00:41:35.546
Which is really remarkable.

743
00:41:35.566 --> 00:41:38.472
The genetic diagnosis really varies by age.

744
00:41:38.492 --> 00:41:42.472
So, when we look at Cochlear Implant patients, this is 100

745
00:41:42.492 --> 00:41:45.472
pediatric Cochlear Implant patients.

746
00:41:45.492 --> 00:41:46.872
Here the diagnostic rate was about 48%.

747
00:41:46.892 --> 00:41:49.803
You can see all the different genes here.

748
00:41:49.823 --> 00:41:53.803
So, GGB 2 is most common.

749
00:41:53.823 --> 00:41:59.803
If you look at adult, the diagnostic rate is lower.

750
00:41:59.823 --> 00:42:01.803
It is about 22%.

751
00:42:01.823 --> 00:42:04.803
This is for a whole number of reasons that I do not have time to

752
00:42:04.823 --> 00:42:08.403
talk about today.

753
00:42:08.423 --> 00:42:10.203
But, the genes that are affected are totally different.

754
00:42:10.223 --> 00:42:12.003
So, that you can see that TMPRS is three.

755
00:42:12.023 --> 00:42:14.603
The whingeing that I talk to you about with Cochlear Implant is the

756
00:42:14.623 --> 00:42:15.603
most common, genetic hearing loss.

757
00:42:15.623 --> 00:42:17.621
In patients who are adults.

758
00:42:17.641 --> 00:42:21.733
So, it really varies based on age.

759
00:42:21.753 --> 00:42:24.733
We also know that genetic diagnosis varies by race and

760
00:42:24.753 --> 00:42:25.233
ethnicity.

761
00:42:25.253 --> 00:42:30.233
So, GJB 2 is most common cause of Caucasian and Asian individuals.

762
00:42:30.253 --> 00:42:35.233
But, it is essentially not present and noncontributory in

763
00:42:35.253 --> 00:42:36.233
African-Americans.

764
00:42:36.253 --> 00:42:41.233
So, if you were to just test for GJB 2 in African-Americans, it

765
00:42:41.253 --> 00:42:46.809
would not be effective.

766
00:42:46.829 --> 00:42:50.809
Dylan Chet the University of San Francisco has done some amazing

767
00:42:50.829 --> 00:42:54.809
work looking at the genetic diagnostic rate based on the

768
00:42:54.829 --> 00:42:57.209
socio-demographic factors.

769
00:42:57.229 --> 00:42:59.209
As well as race and ethnicity.

770
00:42:59.229 --> 00:43:04.209
What he showed is that, Hispanics and Blacks were five times less

771
00:43:04.229 --> 00:43:08.758
likely to receive a genetic diagnosis as Asians and whites.

772
00:43:08.778 --> 00:43:12.758
This is hugely important that we work to reduce this inequity in

773
00:43:12.778 --> 00:43:13.758
genetic testing.

774
00:43:13.778 --> 00:43:16.841
It is a focus in my lab as well as others.

775
00:43:16.861 --> 00:43:18.041
Around the country.

776
00:43:18.061 --> 00:43:21.041
So, just to show you what a diagnostic evaluation would look

777
00:43:21.061 --> 00:43:24.932
like for a child with sensorineural hearing loss.

778
00:43:24.952 --> 00:43:26.932
They have a history of physical exam.

779
00:43:26.952 --> 00:43:29.608
Audio metric testing.

780
00:43:29.628 --> 00:43:34.608
We obtain CNV testing, and we look for specific exam findings.

781
00:43:34.628 --> 00:43:39.608
If we see something that is clearly syndromic, which is often

782
00:43:39.628 --> 00:43:44.608
very difficult in young children, we do genetic testing based on the

783
00:43:44.628 --> 00:43:49.105
syndrome.

784
00:43:49.125 --> 00:43:53.105
… If it is bilateral, including asymmetric hearing loss, and

785
00:43:53.125 --> 00:43:57.105
auditory neuropathy, we start with comprehensive genetic testing.

786
00:43:57.125 --> 00:44:00.162
We obtain an ophthalmology evaluation.

787
00:44:00.182 --> 00:44:03.566
Just make sure there is not a dual sensory impairment.

788
00:44:03.586 --> 00:44:05.968
We get an EKG, because it is cheap and noninvasive.

789
00:44:05.988 --> 00:44:08.968
And we do not want to miss any cardiac problems.

790
00:44:08.988 --> 00:44:11.968
And then we talk to them about imaging.

791
00:44:11.988 --> 00:44:16.968
In the time the -- the timeframe of this peasant weather we are

792
00:44:16.988 --> 00:44:19.968
thinking about a Cochlear Implant or not.

793
00:44:19.988 --> 00:44:22.968
If it is unilateral hearing loss, then essentially, we rely more on

794
00:44:22.988 --> 00:44:26.168
MRI or CT scan.

795
00:44:26.188 --> 00:44:28.768
This is essentially the algorithm I use on a daily basis in my

796
00:44:28.788 --> 00:44:29.268
clinic.

797
00:44:29.288 --> 00:44:31.857
You can see genetic testing forms a cornerstone of it.

798
00:44:31.877 --> 00:44:35.857
However, we have started to wonder whether we should do genetic

799
00:44:35.877 --> 00:44:38.824
testing more for unilateral and asymmetric hearing loss.

800
00:44:38.844 --> 00:44:41.824
So, this is some more recent data just from last year.

801
00:44:41.844 --> 00:44:46.824
Showing that a diagnostic rate by symmetry, if you look at bilateral,

802
00:44:46.844 --> 00:44:48.824
it is about 40%.

803
00:44:48.844 --> 00:44:51.458
Asymmetric, it is about 20%.

804
00:44:51.478 --> 00:44:55.636
Unilateral hearing loss, our diagnostic rate was about 18%.

805
00:44:55.656 --> 00:44:58.636
Maybe what is more important, is the number of syndromic diagnoses

806
00:44:58.656 --> 00:44:59.636
we make.

807
00:44:59.656 --> 00:45:03.636
So, for bilateral symmetric hearing loss, about 20% had

808
00:45:03.656 --> 00:45:05.436
syndromic diagnoses, so this is Usher syndrome or pendulum

809
00:45:05.456 --> 00:45:09.627
syndrome.

810
00:45:09.647 --> 00:45:12.725
But, it was 33% for bilateral asymmetrical hearing loss.

811
00:45:12.745 --> 00:45:15.725
And actually more than half of the individuals be diagnosed who had

812
00:45:15.745 --> 00:45:19.923
unilateral hearing loss, had a syndromic diagnosis.

813
00:45:19.943 --> 00:45:23.923
So, you could argue that the unilateral hearing loss, or

814
00:45:23.943 --> 00:45:28.923
children, they are the ones who the diagnosis is the most important for

815
00:45:28.943 --> 00:45:32.067
because that is what can change our clinical care.

816
00:45:32.087 --> 00:45:36.067
So, this data has really changed how I think about evaluating kids

817
00:45:36.087 --> 00:45:38.067
with unilateral and asymmetric hearing loss.

818
00:45:38.087 --> 00:45:43.067
And I do think we should be performing genetic testing for

819
00:45:43.087 --> 00:45:43.567
them.

820
00:45:43.587 --> 00:45:47.567
So, how do we perform genetic testing for hearing loss?

821
00:45:47.587 --> 00:45:48.767
I told you, there's many companies.

822
00:45:48.787 --> 00:45:53.762
There is a 1 to 3 month test turnaround time.

823
00:45:53.782 --> 00:45:58.762
This can be ordered by an (Unknown term) .

824
00:45:58.782 --> 00:46:03.762
Many of these companies provide genetic counseling associated with

825
00:46:03.782 --> 00:46:04.762
it.

826
00:46:04.782 --> 00:46:05.562
The cost is $1000-$4000.

827
00:46:05.582 --> 00:46:07.762
So, that seems like a lot, and it is a lot.

828
00:46:07.782 --> 00:46:10.762
It will tell you that for our patients, when we looked at the

829
00:46:10.782 --> 00:46:14.762
last 100 patients that we evaluated, 64% of the time insurance actually

830
00:46:14.782 --> 00:46:18.219
covered the genetic testing.

831
00:46:18.239 --> 00:46:20.219
81% of the time with private insurance.

832
00:46:20.239 --> 00:46:24.799
And our mass health actually covered 50%.

833
00:46:24.819 --> 00:46:29.799
So, this is hugely different from 10 years ago when insurance almost

834
00:46:29.819 --> 00:46:30.799
never cover genetic testing.

835
00:46:30.819 --> 00:46:34.799
Now, in the majority of cases, beacons is covered by insurance.

836
00:46:34.819 --> 00:46:38.799
Because insurance companies have realized it is really integral to

837
00:46:38.819 --> 00:46:41.599
care for these individuals.

838
00:46:41.619 --> 00:46:45.599
So, I hope that I have shown to you that by focusing on the diagnosis

839
00:46:45.619 --> 00:46:50.599
instead of the symptom, we are able to decide the best treatment for

840
00:46:50.619 --> 00:46:53.904
the individual.

841
00:46:53.924 --> 00:46:56.904
I want to leave you with some future directions.

842
00:46:56.924 --> 00:46:59.704
So, one thing that I think about, and hopefully I will have a chance

843
00:46:59.724 --> 00:47:02.104
to talk to more about at another forum, is finding a therapeutic

844
00:47:02.124 --> 00:47:05.114
window.

845
00:47:05.134 --> 00:47:11.114
So, we know for things like Cochlear Implant, and I am guessing

846
00:47:11.134 --> 00:47:15.114
for something like gene therapy, that the therapeutic efficacy

847
00:47:15.134 --> 00:47:17.514
decreases over time.

848
00:47:17.534 --> 00:47:21.514
And this is probably a combination of things like the spiral ganglion

849
00:47:21.534 --> 00:47:25.537
neurons and neural plasticity decreases over time.

850
00:47:25.557 --> 00:47:30.537
And then also, when you think about single-sided hearing loss,

851
00:47:30.557 --> 00:47:34.084
there is a side preference that develops.

852
00:47:34.104 --> 00:47:38.084
And what is pretty incredible, is that even at Boston children's,

853
00:47:38.104 --> 00:47:42.084
were we have an incredible amount of resources, our average age at

854
00:47:42.104 --> 00:47:45.419
diagnosis for congenital hearing loss is about 13 months.

855
00:47:45.439 --> 00:47:49.419
So what I mean is, we are providing an actual diagnosis to these

856
00:47:49.439 --> 00:47:52.219
children.

857
00:47:52.239 --> 00:47:54.619
So, this is what our sort of therapeutic window looks like now.

858
00:47:54.639 --> 00:47:57.619
But, in order to improve our therapeutic window for things like

859
00:47:57.639 --> 00:48:00.619
Cochlear Implant and in the future, gene therapy, we need to think

860
00:48:00.639 --> 00:48:04.103
about shifting that diagnosis earlier.

861
00:48:04.123 --> 00:48:10.103
The only way we can do this, is by improving newborn hearing

862
00:48:10.123 --> 00:48:11.103
screening.

863
00:48:11.123 --> 00:48:17.103
Which I know is very important to all of you and very important to me

864
00:48:17.123 --> 00:48:20.503
as well.

865
00:48:20.523 --> 00:48:22.703
So, the take-home points are that hearing loss is a symptom.

866
00:48:22.723 --> 00:48:23.703
It is not a diagnosis.

867
00:48:23.723 --> 00:48:26.703
And a diagnosis for individuals who are deaf and hard of hearing

868
00:48:26.723 --> 00:48:30.703
provides the individual family and the clinician with tons of valuable

869
00:48:30.723 --> 00:48:31.203
information.

870
00:48:31.223 --> 00:48:35.812
And it ultimately allows for personalized care.

871
00:48:35.832 --> 00:48:40.812
And so, I hope you can understand that I have refrained how I think

872
00:48:40.832 --> 00:48:41.612
about this.

873
00:48:41.632 --> 00:48:46.612
And I had district and trying to get other people to think about

874
00:48:46.632 --> 00:48:49.612
this differently.

875
00:48:49.632 --> 00:48:52.212
Instead of looking at the hearing was or coming up with the diagnoses

876
00:48:52.232 --> 00:48:54.412
just so we can start to think about the whole child.

877
00:48:54.432 --> 00:48:57.212
And what is best for the child.

878
00:48:57.232 --> 00:48:59.212
Instead of just their symptom.

879
00:48:59.232 --> 00:49:05.212
And with that, I would like to thank Doctor Kenna, my close… And

880
00:49:05.232 --> 00:49:07.212
everyone in my lap.

881
00:49:07.232 --> 00:49:10.212
Thank you all again for your attention.

882
00:49:10.232 --> 00:49:12.212
I really appreciate it.

883
00:49:12.232 --> 00:49:15.212
I am happy to take questions.

884
00:49:15.232 --> 00:49:16.612
Thank you all again for your attention.

885
00:49:16.632 --> 00:49:17.412
I really appreciate it.

886
00:49:17.432 --> 00:49:18.612
I am happy to take questions.

887
00:49:18.632 --> 00:49:19.612
SPEAKER:  Yes, thank you, Dr.

888
00:49:19.632 --> 00:49:20.112
Shearer.

889
00:49:20.132 --> 00:49:21.312
This is Will Eiserman again.

890
00:49:21.332 --> 00:49:23.112
From the National Center for Hearing Assessment and Management.

891
00:49:23.132 --> 00:49:25.912
And we have some questions coming in and I wanted to start off by

892
00:49:25.932 --> 00:49:28.312
asking you this: it seems like there are so many hot button

893
00:49:28.332 --> 00:49:34.623
issues.

894
00:49:34.643 --> 00:49:36.623
Related to what you talk about today.

895
00:49:36.643 --> 00:49:42.623
And it is important, I would think, that they do not get unnecessarily

896
00:49:42.643 --> 00:49:45.423
conflated.

897
00:49:45.443 --> 00:49:50.340
There is the issue of screening children, genetically, at birth.

898
00:49:50.360 --> 00:49:53.450
Who have hearing loss.

899
00:49:53.470 --> 00:49:55.450
Because that can inform treatment.

900
00:49:55.470 --> 00:49:58.250
Regard us of what the treatment is.

901
00:49:58.270 --> 00:50:03.250
And then there is how it might inform the decision around specific

902
00:50:03.270 --> 00:50:05.012
treatments, like Cochlear Implant.

903
00:50:05.032 --> 00:50:11.012
And then there is that even hotter button issue of whether we should

904
00:50:11.032 --> 00:50:16.213
be going down the path of genetic treatment.

905
00:50:16.233 --> 00:50:22.203
So, can you just say a few more words to try to isolate those

906
00:50:22.223 --> 00:50:23.213


907
00:50:23.233 --> 00:50:29.203
separate concerns so that they do not unnecessarily get conflated?

908
00:50:29.223 --> 00:50:30.686


909
00:50:30.706 --> 00:50:31.186
ELIOT

910
00:50:31.206 --> 00:50:33.186
SHEARER:  Yes, it is a great point.

911
00:50:33.206 --> 00:50:35.424
They are all connected.

912
00:50:35.444 --> 00:50:38.424
But, you can also think about them separately.

913
00:50:38.444 --> 00:50:44.414
So, another way to think about it is that, when we perform genetic

914
00:50:44.434 --> 00:50:45.424


915
00:50:45.444 --> 00:50:49.424
testing, we make sure that families, first of all, want to do the

916
00:50:49.444 --> 00:50:53.270
genetic testing rate.

917
00:50:53.290 --> 00:50:56.270
It is up to the parents, families, and individuals.

918
00:50:56.290 --> 00:50:59.070
That is opting into it.

919
00:50:59.090 --> 00:51:01.470
We never for something like this.

920
00:51:01.490 --> 00:51:05.470
We also want to make sure that we are providing early screening and

921
00:51:05.490 --> 00:51:06.470
the best possible screening.

922
00:51:06.490 --> 00:51:13.307
So, I did not talk about genetic screening.

923
00:51:13.327 --> 00:51:15.307
And hopefully I will add another time.

924
00:51:15.327 --> 00:51:19.307
But, using genetics, I think we will be able to use our newborn

925
00:51:19.327 --> 00:51:24.307
hearing screening by detecting individuals that may have a later

926
00:51:24.327 --> 00:51:27.307
onset hearing less rate outside of the newborn period.

927
00:51:27.327 --> 00:51:32.307
Or there things like auditory neuropathy or other things that may

928
00:51:32.327 --> 00:51:35.322
be missed on the current physiological screen.

929
00:51:35.342 --> 00:51:41.312
So, there is a way to use genetics just for screening.

930
00:51:41.332 --> 00:51:42.914


931
00:51:42.934 --> 00:51:46.914
When you do any screening with genetics though, you will have an

932
00:51:46.934 --> 00:51:52.914
individual who can opt in or opt out ever receiving results.

933
00:51:52.934 --> 00:51:56.914
They may have a screen that says, you failed the genetic portion, do

934
00:51:56.934 --> 00:52:00.521
you want to know the result or not?

935
00:52:00.541 --> 00:52:03.521
So, you can use genetics to just perform a screen without providing

936
00:52:03.541 --> 00:52:06.321
the diagnosis.

937
00:52:06.341 --> 00:52:08.321
I think most families would want to know the diagnosis.

938
00:52:08.341 --> 00:52:10.873
Because of all of the important information it provides you.

939
00:52:10.893 --> 00:52:16.873
But any genetic screen would be -- need to be followed up by a full,

940
00:52:16.893 --> 00:52:20.473
genetic evaluation afterwards.

941
00:52:20.493 --> 00:52:22.873
And then the idea of, you know, gene therapy moving forward with

942
00:52:22.893 --> 00:52:23.373
that.

943
00:52:23.393 --> 00:52:28.373
Again, that can be held totally separately and that is something

944
00:52:28.393 --> 00:52:34.065
that's not going to be available for many or most families.

945
00:52:34.085 --> 00:52:37.065
And so, it is up to the family.

946
00:52:37.085 --> 00:52:38.665
Whether they want to pursue that treatment option.

947
00:52:38.685 --> 00:52:41.065
Just like Cochlear Implant are now.

948
00:52:41.085 --> 00:52:43.065
We would never force that on them.

949
00:52:43.085 --> 00:52:45.065
Does that answer your question, Will?

950
00:52:45.085 --> 00:52:45.565
WILL

951
00:52:45.585 --> 00:52:46.565
EISERMAN:  Yes, thank you.

952
00:52:46.585 --> 00:52:51.565
I know, because I have heard you speak before, about how important

953
00:52:51.585 --> 00:52:57.555
it is for you to make it clear that you are about having as much

954
00:52:57.575 --> 00:52:58.565


955
00:52:58.585 --> 00:53:03.565
information as you can when you consult with families so that they

956
00:53:03.585 --> 00:53:09.598
can make the best decisions that meet their families needs.

957
00:53:09.618 --> 00:53:13.598
And I know that is where you are coming from and I just wanted to

958
00:53:13.618 --> 00:53:18.093
make sure that you had an opportunity to clarify that.

959
00:53:18.113 --> 00:53:21.726
Given how hot some of these other issues are.

960
00:53:21.746 --> 00:53:22.726
ELIOT

961
00:53:22.746 --> 00:53:23.926
    ELIOT SHEARER:  That is exactly right.

962
00:53:23.946 --> 00:53:26.926
I really want to empower patients and families to make the best

963
00:53:26.946 --> 00:53:29.926
decisions for them.

964
00:53:29.946 --> 00:53:30.878
Ultimately.

965
00:53:30.898 --> 00:53:31.378
WILL

966
00:53:31.398 --> 00:53:34.378
EISERMAN:  Here is one of the questions from our participants

967
00:53:34.398 --> 00:53:40.378
today: can you explain why surgeons may be implanting CIs on kids with

968
00:53:40.398 --> 00:53:44.378
no detectable audiological nerve?

969
00:53:44.398 --> 00:53:49.378
This person says, "I have seen no increase in hearing for this

970
00:53:49.398 --> 00:53:49.878
population."

971
00:53:49.898 --> 00:53:50.378
ELIOT

972
00:53:50.398 --> 00:53:50.878
population."

973
00:53:50.898 --> 00:53:51.378
ELIOT

974
00:53:51.398 --> 00:53:53.378
SHEARER:  Yes, that is a great question.

975
00:53:53.398 --> 00:53:55.178
You could have a whole seminar on that (Laughs).

976
00:53:55.198 --> 00:53:57.869
That is totally dependent on the center.

977
00:53:57.889 --> 00:54:02.869
And it is, you know, I can only speak for what we do at Boston

978
00:54:02.889 --> 00:54:07.788
children's, which is, we have an interdisciplinary group.

979
00:54:07.808 --> 00:54:10.788
Of audiologists, speech pathologists, surgeons, social

980
00:54:10.808 --> 00:54:16.778
workers, and we discuss every family and become up with, sort of,

981
00:54:16.798 --> 00:54:19.788


982
00:54:19.808 --> 00:54:22.588
treatment options.

983
00:54:22.608 --> 00:54:26.588
There are some children who have surprised us in that we - it looks

984
00:54:26.608 --> 00:54:31.588
like there is not much of a nerve and they can do very well.

985
00:54:31.608 --> 00:54:34.588
But, it is actually very rare, at our institution, that we would

986
00:54:34.608 --> 00:54:39.353
perform or offer a Cochlear Implant that has no nerve that we can see.

987
00:54:39.373 --> 00:54:41.353
Actually, we essentially do not do that.

988
00:54:41.373 --> 00:54:44.153
I do not want to speak for all groups, but I would not recommend

989
00:54:44.173 --> 00:54:45.501
that.

990
00:54:45.521 --> 00:54:48.501
I know there are some people that proceed with cochlear implantation

991
00:54:48.521 --> 00:54:51.196
if there is no know detectable nerve.

992
00:54:51.216 --> 00:54:57.186
You would need to be able to cancel them really effectively as

993
00:54:57.206 --> 00:54:58.196


994
00:54:58.216 --> 00:55:01.196
far as the risks and benefits.

995
00:55:01.216 --> 00:55:04.196
I hope that answers your question.

996
00:55:04.216 --> 00:55:05.196
WILL

997
00:55:05.216 --> 00:55:07.596
You would need to be able to cancel them really effectively as

998
00:55:07.616 --> 00:55:08.796
far as the risks and benefits.

999
00:55:08.816 --> 00:55:09.996
I hope that answers your question.

1000
00:55:10.016 --> 00:55:10.496
WILL

1001
00:55:10.516 --> 00:55:12.896
You would need to be able to cancel them really effectively as

1002
00:55:12.916 --> 00:55:14.096
far as the risks and benefits.

1003
00:55:14.116 --> 00:55:15.296
I hope that answers your question.

1004
00:55:15.316 --> 00:55:15.796
WILL

1005
00:55:15.816 --> 00:55:18.196
You would need to be able to cancel them really effectively as

1006
00:55:18.216 --> 00:55:21.796
far as the risks and benefits. I hope that answers your question.    WILL EISERMAN:  Here is another question.

1007
00:55:21.816 --> 00:55:22.996
Such interesting questions are coming in.

1008
00:55:23.016 --> 00:55:25.396
Given that congenital CMV is so common, do you also tested those

1009
00:55:25.416 --> 00:55:26.996
patients for genetic causes of sensorineural hearing loss?

1010
00:55:27.016 --> 00:55:28.196
Or just assume it was CMV?

1011
00:55:28.216 --> 00:55:29.196
ELIOT

1012
00:55:29.216 --> 00:55:30.796
    ELIOT SHEARER:  This is such a great question.

1013
00:55:30.816 --> 00:55:32.396
This is a really important topic to me.

1014
00:55:32.416 --> 00:55:35.396
Because exactly as you said, CMV is very common, and genetic hearing

1015
00:55:35.416 --> 00:55:36.396
loss is very common.

1016
00:55:36.416 --> 00:55:40.396
We have now seen several patients were being treated with (Unknown

1017
00:55:40.416 --> 00:55:43.623
Name) for congenital CMV.

1018
00:55:43.643 --> 00:55:45.623
And we perform genetic testing on them.

1019
00:55:45.643 --> 00:55:48.023
And we have actually found they have a genetic cause of hearing

1020
00:55:48.043 --> 00:55:50.132
loss.

1021
00:55:50.152 --> 00:55:55.132
And so, we will stop the treatment for (Unknown term).

1022
00:55:55.152 --> 00:56:01.132
So, our protocol at children's, is any child with hearing loss, we

1023
00:56:01.152 --> 00:56:05.132
recommend they undergo genetic testing if the family is

1024
00:56:05.152 --> 00:56:05.632
interested.

1025
00:56:05.652 --> 00:56:08.505
Because it does change or treatment.

1026
00:56:08.525 --> 00:56:12.505
Because we do not expect (Unknown Name) to help genetic hearing loss,

1027
00:56:12.525 --> 00:56:13.505
for instance.

1028
00:56:13.525 --> 00:56:17.505
I would say even if you think it is congenital CMV, you still need

1029
00:56:17.525 --> 00:56:21.505
to test for genetic hearing loss, and even if you think it is genetic

1030
00:56:21.525 --> 00:56:23.505
hearing loss, you should check for CMV.

1031
00:56:23.525 --> 00:56:25.505
You need to demote -- both.

1032
00:56:25.525 --> 00:56:26.005
WILL

1033
00:56:26.025 --> 00:56:27.405
WILL EISERMAN:  So, CMV does not include

1034
00:56:27.425 --> 00:56:32.621
there being another explanation.

1035
00:56:32.641 --> 00:56:33.121
ELIOT

1036
00:56:33.141 --> 00:56:34.121
SHEARER:  Exactly, yes.

1037
00:56:34.141 --> 00:56:34.621
WILL

1038
00:56:34.641 --> 00:56:38.621
EISERMAN:  The next question, is NTRC on the regular genetic hearing

1039
00:56:38.641 --> 00:56:39.121
panel?

1040
00:56:39.141 --> 00:56:42.614
Would it only connect -- attached deletions?

1041
00:56:42.634 --> 00:56:45.276
What about mutations?

1042
00:56:45.296 --> 00:56:51.276
This person says, "I ask because my sense both have a mutation of

1043
00:56:51.296 --> 00:56:56.276
STRC, not deletion, it was only caught by Columbia's genomic

1044
00:56:56.296 --> 00:56:56.776
project.

1045
00:56:56.796 --> 00:57:01.776
It did not show up on their genetic hearing panel."

1046
00:57:01.796 --> 00:57:02.276
ELIOT

1047
00:57:02.296 --> 00:57:04.534
ELIOT SHEARER:  I alluded to this.

1048
00:57:04.554 --> 00:57:09.534
This gene is very, very difficult to sequence.

1049
00:57:09.554 --> 00:57:15.534
The new technologies we have are getting better and better at

1050
00:57:15.554 --> 00:57:16.534
sequencing.

1051
00:57:16.554 --> 00:57:18.934
So, we have an example of an individual who did the standard

1052
00:57:18.954 --> 00:57:19.434
panel.

1053
00:57:19.454 --> 00:57:20.434
And nothing was detected.

1054
00:57:20.454 --> 00:57:23.434
We did the next level, which was Exim (?

1055
00:57:23.454 --> 00:57:24.652
) sequencing, and nothing was detected.

1056
00:57:24.672 --> 00:57:28.652
And then we did one of those new DNA sequencing technologies I told

1057
00:57:28.672 --> 00:57:33.652
you about, with… sequencing, which are very expensive.

1058
00:57:33.672 --> 00:57:39.652
Finally, that detected an SCRC deletion.

1059
00:57:39.672 --> 00:57:45.642
So, it is very hard to identify and it really depends on new

1060
00:57:45.662 --> 00:57:46.652


1061
00:57:46.672 --> 00:57:50.189
technology.

1062
00:57:50.209 --> 00:57:55.189
I think we are missing some individuals who have… Or deletions.

1063
00:57:55.209 --> 00:58:00.189
Most panels now include detection of deletion… I do not think they

1064
00:58:00.209 --> 00:58:02.789
are capturing all of them, just because it is very difficult to do

1065
00:58:02.809 --> 00:58:07.900
that.

1066
00:58:07.920 --> 00:58:08.400
WILL

1067
00:58:08.420 --> 00:58:09.000
  WILL EISERMAN:  Yes.

1068
00:58:09.020 --> 00:58:12.000
I do not think we will get to all of our questions, let's go for

1069
00:58:12.020 --> 00:58:12.500
another one.

1070
00:58:12.520 --> 00:58:18.500
This is a comment from an individual who identifies as deaf

1071
00:58:18.520 --> 00:58:21.100
since birth.

1072
00:58:21.120 --> 00:58:27.090
The individual says, "I am a carrier of the GJB 2 gene, my

1073
00:58:27.110 --> 00:58:28.100


1074
00:58:28.120 --> 00:58:31.691
partner and children all have the gene.

1075
00:58:31.711 --> 00:58:34.691
I just wanted to share that deafness is the only disability

1076
00:58:34.711 --> 00:58:38.691
that has a culture and language and that I believe it would be

1077
00:58:38.711 --> 00:58:43.691
unethical to do gene therapy to perform eugenics on deafness."

1078
00:58:43.711 --> 00:58:47.691
Do you have a comment about that?

1079
00:58:47.711 --> 00:58:48.191
ELIOT

1080
00:58:48.211 --> 00:58:49.191
ELIOT

1081
00:58:49.211 --> 00:58:49.691
ELIOT

1082
00:58:49.711 --> 00:58:50.191
ELIOT

1083
00:58:50.211 --> 00:58:54.191
SHEARER:  Yes, again, you can spend the whole seminar talking about

1084
00:58:54.211 --> 00:58:57.191
gene therapy, and I hope we do sometime, just so we can better

1085
00:58:57.211 --> 00:59:00.191
educate everyone.

1086
00:59:00.211 --> 00:59:05.191
The way that gene therapy is being talked about for hearing loss, is

1087
00:59:05.211 --> 00:59:06.191
as a treatment.

1088
00:59:06.211 --> 00:59:12.181
So, it is an inject -- injection in the inner ear, does not change

1089
00:59:12.201 --> 00:59:14.191


1090
00:59:14.211 --> 00:59:16.191
the reproductive organs of the individual, for instance.

1091
00:59:16.211 --> 00:59:18.791
That is a common misconceptions.

1092
00:59:18.811 --> 00:59:22.370
Eugenics would be something that actually erases a group of people.

1093
00:59:22.390 --> 00:59:24.770
It is a different treatment option.

1094
00:59:24.790 --> 00:59:27.510
How it is looking right now.

1095
00:59:27.530 --> 00:59:29.110
Similar sort of surgery.

1096
00:59:29.130 --> 00:59:30.110
To cochlear implantation.

1097
00:59:30.130 --> 00:59:31.810
But without the implant.

1098
00:59:31.830 --> 00:59:37.800
So, I would never… I completely respect the opinion of yours.

1099
00:59:37.820 --> 00:59:49.331


1100
00:59:49.351 --> 00:59:50.331
WILL

1101
00:59:50.351 --> 00:59:51.731
    WILL EISERMAN:  There are number of questions.

1102
00:59:51.751 --> 00:59:54.131
Let's maybe end with this question.

1103
00:59:54.151 --> 00:59:57.131
If you have other questions you would like to pose to Dr.

1104
00:59:57.151 --> 00:59:58.331
Shearer, please send them to as.

1105
00:59:58.351 --> 01:00:01.131
We will put that in, Gunner, if you could put my email in --

1106
01:00:01.151 --> 01:00:04.685
address.

1107
01:00:04.705 --> 01:00:09.685
Or the helpdesk in the chat, then we can forward those questions onto

1108
01:00:09.705 --> 01:00:10.185
Dr.

1109
01:00:10.205 --> 01:00:12.145
Shearer.

1110
01:00:12.165 --> 01:00:16.145
There are a number of questions that are coming and that all have

1111
01:00:16.165 --> 01:00:19.145
to do with the statistic that we all here.

1112
01:00:19.165 --> 01:00:23.145
About how many children are born with permanent hearing loss to

1113
01:00:23.165 --> 01:00:29.135
families that do not have a known history.

1114
01:00:29.155 --> 01:00:30.604


1115
01:00:30.624 --> 01:00:34.604
And yet, does that necessarily mean there is a genetic component?

1116
01:00:34.624 --> 01:00:37.910
Can you separate those two issues?

1117
01:00:37.930 --> 01:00:40.863
So that beget a clear understanding of that.

1118
01:00:40.883 --> 01:00:41.363
ELIOT

1119
01:00:41.383 --> 01:00:41.863
ELIOT

1120
01:00:41.883 --> 01:00:44.863
SHEARER:  The majority of genetic hearing loss is recessive.

1121
01:00:44.883 --> 01:00:50.863
Which means that, in most cases, the parents do not have a hearing

1122
01:00:50.883 --> 01:00:53.663
loss.

1123
01:00:53.683 --> 01:00:57.663
It is the combination of the two parents, separate genes, that make

1124
01:00:57.683 --> 01:01:01.329
the child.

1125
01:01:01.349 --> 01:01:02.329
That makes the child different.

1126
01:01:02.349 --> 01:01:07.329
That is a reason why we are not clones of parents, because -- it is

1127
01:01:07.349 --> 01:01:11.329
the parents that make us.

1128
01:01:11.349 --> 01:01:13.329
So, I think that answers your question, well.

1129
01:01:13.349 --> 01:01:13.829
WILL

1130
01:01:13.849 --> 01:01:14.829
EISERMAN:  Yes, thank you.

1131
01:01:14.849 --> 01:01:16.829
It was not mine, it was many others.

1132
01:01:16.849 --> 01:01:20.829
So, we are at the bottom of the hour, which means we are at our

1133
01:01:20.849 --> 01:01:24.229
closure here.

1134
01:01:24.249 --> 01:01:30.229
Before you all run off, Gunner is going to post a link in our chat

1135
01:01:30.249 --> 01:01:35.229
that will take you to a quick survey and a certificate of

1136
01:01:35.249 --> 01:01:38.029
attendance generator.

1137
01:01:38.049 --> 01:01:41.029
So that if you need evidence of your participation in today's

1138
01:01:41.049 --> 01:01:43.815
webinar, you can get that there.

1139
01:01:43.835 --> 01:01:44.315
Dr.

1140
01:01:44.335 --> 01:01:49.315
Shearer, we would love for you to come back and talk specifically

1141
01:01:49.335 --> 01:01:52.915
about the use of genetic screening.

1142
01:01:52.935 --> 01:01:58.164
As a part of the newborn hearing screening protocol.

1143
01:01:58.184 --> 01:02:00.964
And so, we would love to get that on the books sometime soon with

1144
01:02:00.984 --> 01:02:02.641
you.

1145
01:02:02.661 --> 01:02:05.041
If you are open to that.

1146
01:02:05.061 --> 01:02:11.041
Because there is a lot of practical questions about the

1147
01:02:11.061 --> 01:02:14.241
feasibility of doing such a thing.

1148
01:02:14.261 --> 01:02:15.241
ELIOT

1149
01:02:15.261 --> 01:02:17.167
    ELIOT SHEARER:  Yes, I would love to, thank you.

1150
01:02:17.187 --> 01:02:17.667
WILL

1151
01:02:17.687 --> 01:02:18.167
WILL

1152
01:02:18.187 --> 01:02:19.167
WILL

1153
01:02:19.187 --> 01:02:21.696
    WILL EISERMAN:  Yes, thank you, everyone, for your time and attention today.

1154
01:02:21.716 --> 01:02:23.696
This webinar has been recorded.

1155
01:02:23.716 --> 01:02:26.096
And will be posted on infant hearing.org in the next couple of

1156
01:02:26.116 --> 01:02:28.753
days.

1157
01:02:28.773 --> 01:02:33.753
Keep that in mind if you need to review any of this again for your

1158
01:02:33.773 --> 01:02:34.753
own benefit.

1159
01:02:34.773 --> 01:02:39.753
Or if there are individuals who did not attend live today who you

1160
01:02:39.773 --> 01:02:43.290
think might benefit from this information.

1161
01:02:43.310 --> 01:02:45.032
Thank you, everyone.

1162
01:02:45.052 --> 01:02:50.969
And thank you to our captioner, and to our ASL interpreter.

1163
01:02:50.989 --> 01:02:55.969
We really appreciate your talents, expertise, and availability, to

1164
01:02:55.989 --> 01:03:00.969
help us make this webinar, learning opportunity, as accessible as

1165
01:03:00.989 --> 01:03:03.169
possible.

1166
01:03:03.189 --> 01:03:08.413
Thanks, everyone.

1167
01:03:08.433 --> 01:03:08.913
ELIOT

1168
01:03:08.933 --> 01:03:09.913
ELIOT

1169
01:03:09.933 --> 01:03:15.903
    ELIOT SHEARER:  Thank you, thank you to the interpreter and captioner, too.

1170
01:03:15.923 --> 01:03:18.424


1171
01:03:18.444 --> 01:02:08.748
(End of Webinar)