Download Pediatric Hearing Loss

Pediatric Hearing Loss
Introduction
• Hearing loss is common
• 1 in 1000 babies have significant
hearing loss at birth
• 10 in 1000 children have significant
hearing loss at school (inc. mild and
moderate)
• 80% of all children will have at least
one middle ear infection
And Mild Unilateral Hearing
Loss has an Impact...
• Significant reduction
in language
acquisition and
speech with
prolonged mild
unilateral hearing
loss.
http://www.cdc.gov/ncbddd/ehdi/documents/unilateralh
l/Mild_Uni_2005%20Workshop_Proceedings.pdf
Paediatric Sensorineural Loss
• Sensorineural Hearing Loss (Nerve deafness)
– Genetic and Idiopathic (70%)
– Acquired (30%)
• Low birth weight/ NICU residents
• Hyperbilirubinaemia
• Ear and Head trauma
• Anoxia and Hypoxia
• Ototoxic Drugs and Chemicals
• Infectious Diseases
• Recurrent otitis media
Diagnosis
•SWISH (Statewide Infant Hearing
Screening Programme) aims to test
every child born in NSW and identify
significant hearing loss by the age of 3
months
•Parental (other carers) clues
•Family physician
Diagnosis
• History
✦ Risk factors for SNHL
✦ Auditory milestones:
– 3 months: Startled by loud sounds and calmed
by familiar sounds
– 6 months: ability to localise
– 9 months: respond to name & mimic
environmental sounds
– 12 months: First meaningful words
– 18 months: Vocabulary of 20 words or more
– 24 months: Small sentences
Diagnosis
• Examination
– Local
• Auricle
• Canal
• Tympanic membrane
(pneumatic otoscopy)
– Regional
• Syndromic features
– Tuning Forks
• Difficult under 6 yrs
Treatment for Paediatric
Sensorineural Hearing Loss
• Hearing assistive techniques
– Preferential seating
– Techniques to use at home
• Rehabilitation
– Hearing Aids
– FM systems
• Cochlear Implantation
Etiology
 Congenital HL
 50% Genetic
 50% Acquired
 Childhood Onset HL
 50% Genetic
 25% Acquired
 25% Unknown
Genetic HL
 75% non-syndromal
 25% syndromal




75% autosomal recessive (AR)
25% autosomal dominant (AD)
1-2% X-linked
Rare mitochondrial
Autosomal recessive HL
 Monogenic, 25%
risk to offspring if
both parents are
carriers
 Severe to
profound SNHL,
prelingual onset
Autosomal recessive syndromal
HL




Usher syndrome
Pendred
Jervel and Lange Nielsen
Goldenhar (Oculoauriculoverterbral spectrum)
Epidemiology
• congenital SNHL 1-3 per 1000 per live births
• 10x greater for infants with 1 or more risk factor
than those with no risk factors, ie 2% to 5%.
• late-onset and acquired hearing loss in
childhood 6x higher than the incidence of
hearing loss in the neonatal period
• 1% all children have HL
Evaluation
• History:
– intrauterine infections (most commmon prenatal cause)
– perinatal infection, maternal drug abuse, low Apgar score (most common
perinatal causes)
– Prematurity, NICU stay, bilirubinemia,family history.
– Meningitis (most commmon postnatal cause)
• Physical: microscopic exam; auricle, periauricular pits, craniofacial
abnormalities,
• +/- ocular, thyroid, skin, limb exams look for syndromic
cause
Evaluation
• OAE
• ABR
– TORCH, meningitis, family hx, craniofacial abnormalities,
birth weight <1.5kg, neonatal hyperbilirubinemia, Apgar <4
at 1 minutes, <6 at 5 minutes, prolonged NICU stay or
ECMO or mechanical vent, exposure to ototoxic meds.
• Behavior observation audiometry (birth to 6 mos)
• Visual Reinforcement Audiometry (6mos-3yrs)
• Conventional play audiometry (3-6 yrs)
• Standard Audiometry (6 yrs+)
Ancillary Tests
Imaging: CT temporal bone: inner ear disorders,
cholesteatoma, & osteodysplasias.
CBC, lipid profile, IgM assay for TORCH
(Toxoplasmosis, Other[syphilis], Rubella,
Cytomegalovirus, Herpes simplex)
Connexin-26 test
Other tests as indicated by ddx.
Causes of HL
•
•
•
•
•
5-10% prenatal causes (TORCH, teratogens)
5-15% perinatal causes (hypoxemia etc)
10-20% postnatal causes (meningitis etc)
20-30% UNKNOWN
30-50% genetic
Acquired prenatal hearing loss
Congenital Cytomegalovirus
• most common infectious cause, >4000 annual cases
• Incidence of infection: 1-2 cases/100 live birth
 <5% develop multiorgan dx 50% of those develop HL
 5-15% silently infected infants eventually develop HL
• Oto SSx: B progressive high freq SNHL
• Other SSx: Cerebral calcification,
microcephaly, mental retardation,
hepatosplenomegaly, jaundice.
Acquired prenatal hearing loss
Congenital Cytomegalovirus
• Dx: serum anti-CMV IgM, CMV DNA from body
fluid,+ intranuclear inclusions (owl eyes) in renal
tubular cells in urinary sediment (1 to 2 weeks of life)
• Rx: Ganciclovir—little effect for HL since damage
happened already in utero
Acquired prenatal hearing loss
Congenital Syphilis
• Pathophysio: transplacental transmission, 100% inoculation rate
• 40% perinatal death
• Oto SSx Hennebert sign (aka +fistula sign)
– Early deafness birth to 3 yo
– delayed 8-20 yo.
• Other SSx: Hutchinson triad: abnormal central incisors
(aka Hutchinson teeth), interstitial keratitis of the eye,
• Dx: RPR,VDRL(sensitive); FTA-ABS(specific)
• Tx: PCN
Acquired prenatal hearing loss
Congenital Rubella
• Rare since vaccination (0-3 per year now in USA)
• Pathophysio: vasculitis resulting in tissue necrosis
• Oto SSx: B often asymmetric severe to profound
SNHL
• Other SSx: growth delay, learning disability, congenital
heart disease, and ocular, endocrinologic, and
neurologic abnormalities.
• Dx: urine/throat/amniotic fluid clx, antirubella IgM
Inner Ear Dysmorphologies
• Time frame: membranous labyrinth is
interrupted during 1st trimester
• Etiologies: Genetic or teratogenic exposure
• Classifications
– membranous labyrinth ONLY (seen at autopsy)
– Osseous & membranous labyrinth ( seen in CT)
Inner Ear Dysmorphologies
• Incidence: 20% congenital SNHL will show
abnormal inner ear on CT temporal bone
– Bony: Dilated Vestibular aqueduct >cochlea>SCC
(as reflected by modern imaging technology)
Inner Ear Dysmorphologies
membranous labyrinth ONLY
• Complete membranous labyrinthine dysplasia
(Siebenmann-Bing)
• Limited membranous labyrinthine dysplasia
– Scheibe dysplasia (cochleosaccular dysplasia) MOST
common membranous labyrinthine dysplasia
– Cochlear basal turn dysplasia
Bing-Siebenmann
• Extremely rare
• Associated with Jervell and Lange-Nielsen
syndrome and Usher syndrome.
Scheibe dysplasia
cochleosaccular dysplasia
• Pathophysio: incomplete development of the
pars inferior
– Cochlea dysplasia: severa in the basal turn, lessen
toward apex, or severe throughout
– Saccule: collapsed
– Organ of Corti: partial or completely missing
– SCCs & utricle: NORMAL
• OtoSSx: SNHL
• Associated w/ Usher syndrome & Waardenburg
syndrome
.
Cochleosaccular Dysplasia: A Morphometric and
Histopathologic Study in a Series of Temporal Bones.
Sampaio, Andre; Cureoglu, Sebahattin; Schachern,
Patricia; Kusunoki, Takeshi; Paparella, Michael; Oliveira,
Carlos
Otology & Neurotology. 25(4):530-535, July 2004.
FIG. 1. (A) In the apical turn of this right temporal bone from case 10,
there is a large cystic area (arrow) in the stria that intersects in its
apical portion with a hydropic Reissner's membrane (arrowhead). O,
organ of Corti represented by supporting cells; T, deformed tectorial
membrane; S, atrophic stria vascularis. (B) There are strial cysts (arrow)
in the lower basal turn of this left temporal bone from case 2. (C) In the
lower basal turn of this right temporal bone from case 8, there is a
strial concretion (short arrow), a collapsed Reissner's membrane
(arrowhead), and an amorphous substance (long arrow) within a rolled
tectorial membrane.
2
Inner Ear Dysmorphologies
osseous & membranous labyrinth
• Complete labyrinthine aplasia
(Michel) 1%
• Cochlear anomalies
– Cochlear aplasia 3%
– cochlear hypoplasia 15%
– Incomplete partition (Mondini)
55%
– Common cavity 26%*
*Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: a classification
based on embryogenesis, Laryngoscope Suppl 97:2, 1987
Michel: complete labyrinthine Aplasia
• Exceedingly rare.
• Associated w/
anencephaly &
thalidomide exposure.
• Overestimated due to
confusion with
acquired labyrinthine
ossification.
Mondini: incomplete partition
• Pathphysio: arrest at 7th week gestation 1.5
turn cochlea
• Oto SSx: normal to profound SNHL
• Other SSx:
– 20% SCC deformities;
– dilated cochlear aquaduct: perilymphatic gushers &
meningitis
Mondini: incomplete partition
• CT/MRI findings:
– smaller cochlea (5-6mm vs 8-10mm vertical
dimension of normal cochlea)
– absence of a scalar septum
Common Cavity
• Pathphysio: arrest at 4th week otocyst stage or
later
• CT/MRI findings:
– Empty ovoid space (average 7mm vertically, 10mm
horizontally)
– Common cavity cochlear ANTERIOR to the IAC
on axial CT
• Oto SSx: variable SNHL, usually poor
Common Cavity
Implanting Common Cavity Malformations Using
Intraoperative Fluoroscopy.
Coelho, Daniel; Waltzman, Susan; Roland, J
Otology & Neurotology. 29(7):914-919, October 2008.
DOI: 10.1097/MAO.0b013e3181845827
FIG. 2 . A transorbital plain x-ray intraoperative view. Note that the array has
passed into the IAC. The arrow denotes the junction between the common
cavity and the IAC as seen in this orientation. Inset outlines the lumen of the
common cavity (cc) and the IAC. Reprinted with permission from Fishman AJ,
Roland JT Jr, Alexiades G, Mierzwinski J, Cohen NL. Fluoroscopically assisted
cochlear implantation. Otol Neurotol 2003;24:882-6.
2
Inner Ear Dysmorphologies
osseous & membranous labyrinth
• Labyrinthine anomalies
– Semicircular canal dysplasia
– Semicircular canal aplasia
• Aqueductal anomalies
– Enlargement of the vestibular
aqueduct
– Enlargement of the cochlear
aqueduct
•
Internal auditory canal
anomalies
– Narrow IAC
– Wide IAC
*Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: a classification
based on embryogenesis, Laryngoscope Suppl 97:2, 1987
Semicircular Canal Dysplasia
• 40% malformed
cochlea a/w dysplasia
of lateral SCC
– Lateral>>post/superi
or
• Pathphysio: arrest at
6th week
• CT/MRI findings :
short, broad cystic
space confluent with
the vestibule
Enlargement of the Vestibular Aqueduct
• Epid: most common radiographically detectable
malformation of the inner ear
• Pathphysio: Acquired abnormal communication
between the subarachnoid space and the fluid chambers
of the inner ear
• Oto SSx:
– born w/ normal or mildly impaired hearing that gradually
worsens;
– hearing variable, 40% profound SNHL
– CHL possible: AVOID STAPEDECTOMY! (a/w
perilymphatic gusher)
Enlargement of the Vestibular Aqueduct
• CT/MRI findings :
–
–
–
–
CT: VA> 2mm (normal 0.4-1mm)
a/w cochlea or SCC malformation
MRI: Dilated endolymphatic sac, sometimes >2cm
Usually bilateral
• RX: CI, avoid endolymphatic
surgery/stapedectomy
Wide Internal Auditory Canal
• Usually incidental finding in normal hearing
subjects
• CT/MRI findings : IAC>10mm
• a/w spontaenous CSF otorrhea & gusher during
stapes surgery obtain CT for congenital CHL!
Narrow Internal Auditory Canal
• Pathphysio : agenesis of CN VIII
• CT/MRI findings : IAC<3 mm, bony canal only
transmits CN VII
• Relative contraindication to CI
GENETIC HL
• >50% non-syndromic
– 75% to 80% autosomal recessive
– 15% to 20% autosomal dominant
– 1% to 2% is X-linked.
– <<1% mitochondrial inheritance
Autosomal Recessive Disorders
Usher syndrome
• Most common cause of congenital deafness
• 50% deaf-blind in USA
• Pathophy: unknown, could also be autosomal
dominant, X-linked
• SSx:Variable SNHL, progressive retinitis pigmentosa
• Dx: Electroretinography
Usher syndrome
subtypes
• I: profound congenital SNHL, No vestibular response
Blind by childhood, most common
• II: moderate to severe SNHL, normal vestibular
response, blind by early adulthood
• III: progressive SNHL, progressive vestibular
dysfunction, varied progression in blindness
Autosomal Recessive Disorders
Pendred syndrome
• Pathophy: Defect in tyrosine iodination from pendrin
(chloride/iodide transporter)
• OtoSSx: severe to profound SNHL, a/w Mondini
deformity, dilated vestibular aqueducts.
• Other SSx: multinodular goiter in 8-14 yo
• Dx: + perchlorate test
• Rx: Thyroid supplement
Autosomal Recessive Disorders
Jervell and Lange-Nielsen Syndrome
• Pathophy: mutation in potassium channel
• OtoSSx: B severe to profound SNHL
• Other SSx: cardiac abnormalities, recurrent syncope,
sudden death
• Dx: EKG ( prolonged QT, large T-wave)
• Rx: beta-blocker, HA
Autosomal Recessive Disorders
Goldenhar Syndrome
• aka Hemifacial Microsomia/ Oculoauriculovertebral
spectrum
• Pathophy: uncertain, malformation of 1st and 2nd arch
derivatives
• OtoSSx:
– microtia/EAC atresia, ossicular malformationCHL
– abnormal CN VII, SCC, oval windowSNHL
Autosomal Recessive Disorders
Goldenhar Syndrome
• Other SSx:
–
–
–
–
Ocular: epibulbar dermoids, colobomas of upper eyelids
Vertebral: fusion or absence of cervical vertebrae
Facial asymmetry
Mild mental retardation
• Dx: PE
Autosomal Dominant Disorders
Waardenberg Syndrome
• Pathophy: abnormal tyrosine metabolism
• OtoSSx: U/B SNHL, +/- vestibular dysfunction
• Other SSx:
– Pigmentary abnormalities
(heterchromic iriditis,
white forelock,
patch skin depigmentation
– Dystopia canthorum
– Synophrys
– Flat nasal root,
– Hypoplastic alae
Autosomal Dominant Disorders
Waardenberg Syndrome
•
•
•
•
Subtypes
I: + telecanthus, 36-66.7% SNHL
II: -telecanthus, 57-85% SNHL
III: type 1 + hypoplasia or contracture of the upper
limbs. (=Klein-Waardenburg syndrome)
• IV: WS + Hirschsprung disease (Waardenburg-Shah
syndrome) autosomal recessive
• Dx: clinical H&P, family Hx
Autosomal Dominant Disorders
Stickler Syndrome
• =Progressive Arthro-Ophthalmpathy
• Pathophy: mutation in type II and type XI collagen, variable
phenotype; 1:10,000
• OtoSSx: progressive SNHL, MHL ( from ETD of clefting)
• Other SSx:
– myopia, retinal
detachment
– Marfanoid habitus
– joint hypermobilities
– Midline clefting
• Dx: clinical H&P, family Hx
Autosomal Dominant Disorders
Branchio-Oto-Renal Syndrome
• =Melnick Fraser Syndrome, 1 in 40,000 newborns
• Pathophy: branchial arches, otic & renal abnormal development
• OtoSSx:
– preauricular ear pits/tags, microtia, EAC stenosis; middle/inner ear
anomalites
– 50% MHL, 30% CHL, 20% SNHL
• Other SSx: varied renal abnormalities (agenesis to mild dysplasia)
• Dx: Renal US or pyelography; renal abnormalities frequently
asymptomatic
Autosomal Dominant Disorders
Treacher Collins Syndrome
• =Mandibulofacial dysostosis
• Pathophy: uncertain.
• OtoSSx: microtia/EAC atresia, preauricular fistulas, malformed
ossicle CHL, widened aqueduct, aberrant CN VII
• Other SSx: mandibular hypoplasia-fishmouth; downward
slanting palpebral fissures, coloboma of lower eyelids, palate
defects. Choanal atresia
• Dx: clinical H&P, family Hx
• Rx: BAHA, possible atresia repair
Autosomal Dominant Disorders
Neurofibromatosis I
•
•
•
•
=Von Recklinghausen disease
Pathophy: NF 1 in chromosome 17
OtoSSx: retrocochlear HL
NF 1 (2/7 characters)
–
–
–
–
–
–
–
>6 café-au-lait spots
2 or more neurofibromas or 1 plexiform neurofibroma
Axillary or groin freckling
Optic nerve glioma
Lisch nodules (eye hamartomas)
Bony lesions
+family Hx
• 5% risk of U vestibular schwannoma
Autosomal Dominant Disorders
Neurofibromatosis 2
• Pathophy: mutation in Merlin ( tumor suppressor gene) in chromosome 22
• OtoSSx: retrocochlear HL
• NF 2
– B vestibular schwannoma by 2nd decade of life
– Family h/o NFII in a 1st degree relative PLUS
– A) unilateral vestibular schwannoma at <30 yo
– B) 2 neurofibroma + other intracranial & spinal cord tumors
(gliomas/schwannomas/meningiomas)
Autosomal Dominant Disorders
Apert Syndrome
• =Acrocephalosyndactyly
• Pathophy: autosomal dominant or sporadic
• OtoSSx: Stapes fixation CHL, patent cochlear aqueduct, large
subarcuate fossa
• Other SSx:
– lobster claw hands
– midface abnormalites (hypertelorism, proptosis,
saddle nose, high-arched palate)
– craniofacial dysostosis
– trapezoid mouth
Autosomal Dominant Disorders
Crouzon Syndrome
• = Craniofacial dysostosis , Pathophy: unknown
• OtoSSx: microtia/EAC atresia, malformed ossicle CHL,
• Other SSx: midface abnormalites (hypertelorism, small maxilla,
exophthalmos, parrot nose, short upper lip, craniofacial
dysostosis, mandibular prognathism
Sex-linked Disorders
Alport Disease
• Pathophy: 80% X-linked or autosomal dominant/recessive.
Abnormal Type IV collagen formation in glomerular basement
renal failure
• OtoSSx: B degeneration of organ of Corti and stria slowly
progressive SNHL
• Other SSx: hematuria, progressive nephritis, macular/corneal
lesions
• Dx: skin or renal bx w/ electron microscopy, UA
• Rx: HD, renal transplant.
What Causes Hearing Loss?
Non-Genetic
• Infections
• Drug-Related
• Traumas/
Exposures
• Structural
Genetic
• Unknown
How Genetic HL occurs?
Chromosomes in Nucleus
23 Pairs of Chromosomes
MOM
DAD
One Chromosome Pair
Genes
“instruction manual”
Genes
Chromosome Pair
Genes
Mutation
“error”
How Is Mutation Inherited?
•
•
•
•
Dominant ~15%
Recessive ~80%
X-Linked ~2%
Mitochondrial >2%
Dominant Inheritance
Mutation
“error"
Carrier
Mutation
“error"
How a Recessive Mutation is
Passed?
Carrier –No Hearing Loss
Affected Child—
Hearing Loss
Carrier –No Hearing Loss
Recessive Inheritance
90% of all children w/HL
have normal hearing parents!
Dominant Inheritance
Recessive Inheritance
Parent w/o HL
Parent w/HL
Parent w/o HL
Child w/HL
If a parent has a dominant
mutation, EACH of their children
has a 50% chance of having
hearing loss
Child w/ HL
If two parents have a recessive
mutation, EACH of their children
has a 25% chance of having
hearing loss
HOW? WHO? WHY?
HOW
Do We Know If HL is Genetic?
WHO
Should Have a Genetic Test?
•
Everybody with Sensorineural HL
Also 2 Mutations in Cx26!!
WHY
Should We Have a Genetic Test??
Benefits for Genetic Testing
• a definite cause
• family members realize that they are carriers &
determine risk factors for future children
• helps to find appropriate treatment/
management
Limitations for Genetic Testing
• does not necessarily find the answer
• severity of HL may not be predicted
• a person may have mutations, but not have HL
Things to Consider
1. Talk to knowledgeable professional
 Primary Care/ Pediatrician
 Clinical Geneticist
 ENT
 Genetic Counselor
 Audiologist
 Clinical Molecular Geneticist
Things to Consider
2. What tests are done?
•
•
•
•
3. Cost
Cx26
Cx30
Mitochondrial Tests
Pendred
UNDERSTANDING
TEST RESULTS
(example Cx26)
What Does the Result Mean?
• Two Mutations are Found
~18%
• Mutations w/Unknown
Significance
??
~1%
• No Mutations are Found
~70%
• One Mutation is Found
~10%
One Mutation Found
•
•
•
•
Mutation unrelated to deafness
Test did not find 2nd mutation
Dominant mutation
There may be a mutation in another gene
Future in Genetics and HL
• More Genetic Tests
GeneChip Technology
Research Studies
• Connexin 26 Study- individuals with Cx26 mutations
• Genetic Testing and Counseling Study - If you or your child
has had genetic testing for hearing loss and you are willing to fill
out a questionnaire
• GeneChip Study - individuals with hearing loss who and
parents with normal hearing
• Novel Gene Discovery Study - five or more family members
with hearing loss