Congenital hearing loss - UCSF CME · 2013-11-26 · Congenital hearing loss Which tests and why does it matter? Dylan K. Chan, MD, PhD Assistant Professor Pediatric Otolaryngology

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Congenital hearing lossWhich tests and why does it matter?

Dylan K. Chan, MD, PhDAssistant ProfessorPediatric OtolaryngologyUniversity of California, San Francisco

UCSF Otolaryngology UpdateSaturday, November 9, 201311:30-11:50 am

I have nothing to disclose

Congenital hearing loss Outline

How are children identified? Newborn hearing screening, school screeningWhy to work up? Knowledge, prognosis, counseling, interventionHow to work up? History, physical, diagnostic testingWhich tests to consider? Imaging, genetic testing, CMVHow to decide? Audiogram, cost, side effects, impact

Goal is not to provide a strict workup algorithm, but to build understanding to facilitate informed counseling of patients and families

Newborn Hearing Screening Goals

Birth AABR or DPOAE- based screen (x2 to confirm)

By one month Outpatient screen/rescreen

By three monthsDiagnostic audiology evaluation (ABR)Otolaryngology evaluation

By six monthsCommunity/school services initiatedOngoing audiology/otolaryngology management

REFER

REFER

Confirmed hearing

loss

Goal diagnosis, medical treatment, and early intervention initiated by 6 months.

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Newborn Hearing Screening Outcomes

Each year in CA:

500,000 infants screened 93% of all births in CA

10,000 infants (1:50) REFER Diagnostic program initiated

1,000 infants (1:500) diagnosed with Congenital SNHL http://trialx.com

Newborn Hearing Screening Outcomes

Each year in CA:

500,000 infants screened 93% of all births in CA

10,000 infants (1:50) REFER Diagnostic program initiated

1,000 infants (1:500) diagnosed with Congenital SNHL

Plus an additional 1:500 children with postnatal permanent childhood hearing impairment (PCHI)

http://trialx.com

All children with SNHL

50% acquired 50% genetic

67% non-syndromic33% syndromic

50% GJB2

50%Non-GJB2

Congenital Sensorineural Hearing Loss Epidemiology

Pendred’sUsher’s

CMVTORCH

infections

All children with SNHL

50% acquired 50% genetic

67% non-syndromic33% syndromic

50% GJB2

50%Non-GJB2

Congenital Sensorineural Hearing Loss Epidemiology

Pendred’sUsher’s

CMVTORCH

infections

Early intervention + hearing aids or cochlear implantation

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Congenital Sensorineural Hearing Loss Why test?

Knowledge


Knowledge Why can’t my child hear?



Prognosis



Prognosis Is the hearing going to get worse?

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Exclusion of other causes




Exclusion of other causes What else is wrong with my child?





Family counseling





Family counseling What does this mean for my other kids?

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Intervention






Intervention What can we do about it?

Congenital Sensorineural Hearing Loss How to work up?

HistoryPhysical ExamDiagnostic Tests

History Syndromic hearing loss

Associations with syndromic SNHL apparent from personal or family history

Visual impairment Usher’sBranchial cleft anomalies Branchio-oto-renalThyroid dysfunction/goiter Pendred’sSudden death/arrhythmia Jervell Lange-NielsenRenal/urinary complaints Alport’s, branchio-oto-renalPigmentation disorders Waardenburg

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History Non-syndromic hearing loss

Causes of non-syndromic SNHL apparent from history

Infectious Toxoplasmosis, syphilis, rubella, CMV, HSV, meningitis

Ototoxic drugs Gentamicin, cisplatinGenetic Family history, consanguinityHyperbilirubinemia JaundiceTrauma EVA-related sudden hearing loss

Physical Exam Syndromic hearing loss

Associations with syndromic SNHL apparent from physical exam

Goiter Pendred’sCraniofacial abnormalities MultipleBranchial cleft anomalies Branchio-oto-renalPreauricular pits Branchio-oto-renalPigmentation abnormalities Waardenburg’s

Diagnostic tests Congenital hearing loss

What next?

1) Work up potential causes revealed in H&P• Visual loss -> ophthalmology consult• Urinary problems -> renal US• Branchial cleft anomalies -> renal US• Goiter or thyroid problems -> TFTs, genetic testing (SLC26A4), imaging (EVA)• History of syncope or arrhythmia -> EKG• ANY syndromic association -> genetics consult

Diagnostic tests Congenital hearing loss

What next?

1) Work up potential causes revealed in H&P• Visual loss -> ophthalmology consult• Urinary problems -> renal US• Branchial cleft anomalies -> renal US• Goiter or thyroid problems -> TFTs, genetic testing (SLC26A4), imaging (EVA)• History of syncope or arrhythmia -> EKG• ANY syndromic association -> genetics consult

2) If H&P unrevealing:• do NOT empirically pursue these tests for specific syndromic causes.• DO consider one of three core diagnostic tests

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Non-syndromic hearing loss Core diagnostic tests

1) Imaging1) CT2) MRI

2) Genetic testing1) Connexin 26/302) Pendred’s3) Usher’s4) Complete hearing loss gene array testing

3) CMV testing1) Urine PCR (active infection)2) Newborn blood spot PCR (congenital infection)




3) CMV testing1) Urine PCR (active infection)2) Newborn blood spot PCR (congenital infection)

Bony anomalies CT

Right: http://www.nidcd.nih.gov/health/hearing/pages/eva.aspxLeft: http://american-hearing.org/disorders/congenital-deafness/

Enlarged vestibular aqueductMondini dysplasia

Bony anomalies MRI vs. CT

Right: http://www.nidcd.nih.gov/health/hearing/pages/eva.aspx

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Nerve anomalies MRI

Oblique sagittal plane FIESTA MRI – internal auditory canal

Normal anatomy Cochlear nerve aplasiaYan et al., 2013

Nerve anomalies CT

Normal anatomy Cochlear nerve aplasia

Narrowing of IACNot always seen on CT

(~50% of cases of known, MRI-demonstrated cochlear nerve hypoplasia)

Yan et al., 2013

Nerve anomalies CT

Yan et al., 2013

Narrowing of cochlear nerve canal <1.5 mmSlightly more demonstrable on CT than IAC narrowing

(~70% of cases of known, MRI-demonstrated cochlear nerve hypoplasia)

Imaging CT vs MRI

CT

Somewhat better bony anatomy

MRI

Much better neural anatomy

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Imaging Side effects and costs

CT

Somewhat better bony anatomy

RadiationLess sedation

Less expensive

MRI

Much better neural anatomy

No radiationMore sedation

More expensive

Imaging CT and MRI risk

Miglioretti et al., 2013

Single anesthetic exposure before age 3

Ing et al., 2012

Up to 1:570 risk of cancer with a single head CT under 5 years

Two-fold risk of neurocognitive disability with single anesthetic under 3 years

Could not adjust for disease confounder

Imaging Impact

How does information gleaned from imaging affect patient management?

EVA recommendations regarding head trauma

Temporal-bone abnormalities surgical planning

Cochlear nerve hypoplasia cochlear implant candidacy

Imaging CT vs MRI

Recommendations

1) Cochlear implant candidates MRI with or without CT

2) All others MRI or CT at appropriate age after discussion with parents

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3) CMV testing1) Blood/urine PCR (active infection)2) Newborn blood spot (congenital infection)

Genetic testing GJB2/GJB6

1/2000 general population1/10-1/50 carrier frequency

20% of congenital SNHL20% of patients with postnatal permanent childhood hearing impairment20% progressive20% asymmetric

Strong association of ethnicity with mutation, prevalence, and hearing

35delG

R143W

235delCV37IW24X

167delCcIVS1+1G>A

Cx26 hearing loss Common mutations

Chan et al., 2013

Cx26 hearing loss Severity

0%

50%

100%

T/T NT/T NT/NT

profound

severe

moderate

mild

N = 1531 Snoeckx et al., 2006

Perc

ent o

f ind

ividu

als

Genotypei.e. 35delG i.e. V37I

% of

all Cx

26 he

aring

loss

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Cx26 hearing loss Progression

Chan et al., 2010

Perc

ent o

f ind

ividu

als

Genotype

* p < 0.01

Genetic testing Disease-specific panels

Gene Location #genes tested

Turnaround time

Cost (approximate)

Indication

GJB2/GJB6 (Connexin 26)

Stanford,multiple

2 1-3 wks $400 Non-syndromicSNHL

SLC26A4(Pendred’s)

Stanford, Cincinnati, Boston

1-3 4 wks $1100 SNHL + EVA or thyroiddysfunction

Usher’s panel Cincinnati,Boston

9 8-12 wks $2500 SNHL + visual dysfunction

Genetic testing Next-generation sequencing arrays

Platform Location #genes tested

Turnaround time

Cost (approximate)

OtoSeq Cincinnati 23 12 wks $3500 (self)$4300 (insurance)

OtoGenome Boston 70 8-12 wks $4000

OtoScope Iowa 66 6 months $1500

Genetic Testing Impact

Any cause identified genetic counseling/family planning

Syndromic association identified careful screening for associated phenotype

Specific mutations increased risk of progressive hearing loss, ototoxicity

Future therapeutic options gene therapy

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3) CMV testing1) Urine PCR (active infection)2) Newborn blood spot (congenital infection)

Congenital CMV infection1:500 newborns (higher with lower socioeconomic status)

CMV Epidemiology

10% symptomatic

30-65% SNHL

90% asymptomatic

7-15% SNHL (by age 6)

Overall 20-30% of CMV (+) with SNHL

10-60% of SNHL with CMV (+)Misono et al., 2011

Prenatal healthy pregnant women and newborns not routinely tested for CMV

Newborn screening saliva PCR assays (not routinely done)

Neonatal (up to three weeks) PCR assay from urine or blood

Postnatal PCR assay from dried heel sticks performed for newborn screening

CMV Testing options

Prognosis High risk of progressive hearing loss

Treatment IV ganciclovir, PO valganciclovir. Side effects, unclear treatment window

Cochlear implantation Overall benefit, but outcomes worse

CMV Impact

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2) Genetic testing1) Connexin 26/302) Pendred’s3) Ushers4) Complete hearing loss gene array testing

3) CMV testing1) Urine PCR (active infection)2) Newborn blood spot (congenital infection)

Core diagnostic tests How to choose?

1) Diagnostic yield 2) Audiogram configuration 3) Cost4) Side effects5) Potential for intervention/changes in management


Test Imaging Genetics CMV

Diagnosticyield

10-30%Audiogram dependent

10-30%Ethnicitydependent

10-30%Region dependent

Audiogram (Unilateral HL)

+++ + ++

Cost + (CT)++ (MRI)More with sedation

+ (Cx26)+++ (full screen)

+ (urine PCR)? (blood spot)

Risks/side effects

++/+++ + +

Impact +++ (for CI)+ (for others)

++ +++ (for neonates)+ (for others)


Cochlear implant candidate MRI/CT -> Cx26/CMV

Unilateral imaging at appropriate age -> Cx26/CMV

All others Cx26/CMV -> imaging at appropriate age. Consider demographics.

If no findings, consider full genetic array testing

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Cochlear implant candidate MRI/CT -> Cx26/CMV

Unilateral imaging at appropriate age -> Cx26/CMV

All others Cx26/CMV -> imaging at appropriate age. Consider demographics.

If no findings, consider full genetic array testing

Discuss with parents!

Thanks

Congenital hearing loss - UCSF CME · 2013-11-26 · Congenital hearing loss Which tests and why does it matter? Dylan K. Chan, MD, PhD Assistant Professor Pediatric Otolaryngology

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