Download Congenital Hearing Loss

Congenital Hearing Loss
Ashley Starkweather, MD
UCLA Head and Neck Surgery
February 25, 2009
Etiology
 Congenital HL
 50% Genetic
 50% Acquired
 Childhood Onset HL
 50% Genetic
 25% Acquired
 25% Unknown
Genetic HL
 75% non-syndromal
 25% syndromal
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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
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Usher syndrome
Pendred
Jervel and Lange Nielsen
Goldenhar (Oculoauriculoverterbral
spectrum)
Usher Syndrome
 Retinitis pimentosa and SNHL
 Night blindness > field cut > central
blindness
 Most common cause of congenital deafness
 Dx: electroretinography
Usher Types
 Type I (most common):
 Profound SNHL, no vestibular fxn
 RP onset in early childhood
 Atypical myosin (myosin 7A): interferes with
mechanoelectrical transduction in labyrinthine hair cells
 Type II:
 Congenital sloping SNHL
 Normal vestibular fxn
 RP onset in teens
Usher Types
 Type III:
 Progressive SNHL and vestibular dysfunction
 Vestibulocerebellar ataxia
 Type IV:
 Mental retardation and hypotonia
Usher
Pendred Syndrome
 Defect in tyrosine iodination
 Gene mutation: affects pendrin, molecule involved
in chloride-iodine transport
 Sx: severe to profound SNHL, multinodular goiter
in childhood
 Assoc with Mondini malformation and enlarged
vestibular aqueduct
 Dx: (+) perchlorate test
 Tx: thyroid hormone to suppress goiter
 Transverse CT scans of
the middle ear in a 47year-old patient with
Pendred syndrome.
 (a) Modiolus is not
discernible (short arrow).
Vestibular aqueduct
(arrowheads) and
vestibule (long arrow) are
enlarged.
 (b) Interscalar septum
between upper and middle
turn of the cochlea is
absent (arrow).
Jervell and Lange Nielsen
 Congenital profound SNHL
 Prolonged QT interval with syncope,
sudden death
 Gene mutation: KVKQT1 = abnormal K+
channel
 Dx: EKG
 Tx: Beta blockers, hearing aids
Goldenhar Syndrome
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First and second arch derivatives, hemifacial
CHL and SNHL (mixed)
Ocular: epibulbar dermoids, colobomas
Auricular: preauricular appendages, pinna
abnormalities, EAC atresia, ossicular
malformation/absence, abnormal facial nerve,
stapedius, semicircular canals and oval window
 Vertebral: fusion/absence of cervical vertebrae
Goldenhar Syndrome
Autosomal Dominant
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Vertical pattern of inheritance
Risk to offspring of 50% if 1 parent affected
Variable penetrance and expressivity
Often postlingual hearing loss, progressive
AD Syndromes
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Waardenburg
Treacher Collins
Apert
Crouzon
Stickler
Neurofibromatosis
Brancio-oto-renal
Waardenburg Syndrome
 Abnormal tyrosine
metabolism
 Pigment abnormalities:
heterochromic iriditis,
white forelock, patchy
skin depigmentation
 Craniofacial
abnormalities: dystopia
canthorum, synophrys,
flat nasal root
Waardenburg Types
 Type I:
 Dystopia canthorum, pigment and craniofacial
abnormalities, 20% with SNHL
 Mutation in PAX3 gene
 Type II:
 No dystopia canthorum, 50% with SNHL but
not as severe
 MITF mutation
Waardenburg Types
 Type III (most severe):
 Unilateral ptosis and skeletal abnormalities
 PAX3 mutation
 Type IV:
 Type II plus Hirschsprung’s disease
(aganglionic megacolon)
Treacher Collins
(Mandibulofacial dysostosis)
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Hypoplasia of mandible and facial bones
Downsloping palpebral fissures, colobomas
Atretic external and middle ear
Mixed HL
Cleft palate (35%)
Gene mutation on chr 5q: TCOF1 codes for a cell
transport protein (treacle)
 Tx: BAHA, bone conduction HA, surgical
correction of aural atresia
Treacher Collins
Apert Syndrome
(Acrocephalosyndactyly)
 Middle and inner ear affected
 Stapes fixation (CHL), patent cochlear
aqueduct, large subarcuate fossa
 Hand syndactyly, midface abnormalities,
craniofacial dysostosis, trapezoid mouth
Apert
Crouzon Syndrome
(craniofacial dysostosis)
 Atresia and stenosis of EAC, CHL,
ossicular deformities
 Cranial synostosis, small maxilla,
exophthalmos, parrot nose, short upper lip,
mandibular prognathism, hypertelorism
 Abnormal FGF receptors
Crouzon
Stickler Syndrome
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Progressive Arthro-Ophthalmopathy
Progressive SNHL (80%)
Marfanoid body habitus
Severe myopia, retinal detachment
Flat midface
Hypermobile joints
Pierre Robin sequence: micrognathia,
glossoptosis, cleft palate
Neurofibromatosis
 NF-1 (Von Recklinghausen Disease)
 Café au lait spots, neurofibromas, Lisch nodules, 5%
risk of unilateral acoustic neuroma
 NF-1 gene on Chr 17
 NF-2 (central neurofibromatosis)
 Bilateral acoustic neuromas or unilateral with 1st
degree relative with NF-2 or multiple central
schwannomas
 NF-2 gene Chr 22q12 (tumor suppressor gene
mutation)
NF-1
Branchio-oto-renal
(Melnick Fraser Syndrome)
 Renal abnormalities: mild hypoplasia to bilateral
aplasia
 Branchial cleft cyts
 Preauricular pits
 EYA1 on Chr 8q13
 Hearing loss:
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Penetrance: 80%
Mixed: 50%
Conductive: 30%
SNHL: 20%
X-linked Disorders
 Alport’s syndrome
 Otopalatal-digital
 Norrie syndrome
Alport’s Syndrome
 X-linked 80%, autosomal
dominant 20%
 Progressive
glomerulonephritis and
SNHL
 Abnormal type IV
collagen in GBM; gene
COL4A5
Alport’s Syndrome
 Bilateral degeneration of organ of Corti and
stria vascularis
 Ocular disorders (myopia, cataracts)
 Dx: UA, BUN, Cr
 Tx: dialysis, renal transplant
Otopalatal-digital
 Ossicular malformation (CHL)
 Palate defects
 Digital abnormalities: broad fingers and
toes
 Hypertelorism, short stature, mental
retardation
Otopalataldigital
Norrie Syndrome
 Blindness
 Progressive mental retardation
 Hearing loss
Mitochondrial Disorders
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Follows maternal line
Postlingual HL
Associated with systemic metabolic disorders
Increased sensitivity to aminoglycoside ototoxicity
Ex:
 MELAS: mitochondrial encephalopath, lactic acidosis,
and strokelike syndrome
 MIDD: maternally inherited diabetes and deafness
Acquired Congenital HL
 Prenatal: infections, teratogens
 Perinatal: NICU admission
 Postnatal: infections, neoplasms
Prenatal Infections
 TORCHS:
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Toxoplasmosis
Rubella
CMV
HSV encephalitis
Syphilis
Rubella
Cataracts, cardiac defects, HL
 Atrophy of Organ of Corti,
thrombosis of stria vascularis,
loss of hair cells, endolymphatic
hydrops
 Anemia, metal retardation, LE
deformities, microcephaly,
thrombocytopenia
 Dx: culture virus from urine,
throat or amniotic fluid;
antirubella IgM
CMV
 1-2% of live births
 Only 10% have HL
 Hemolytic anemia, microcephaly, mental
retardation, HSM, jaundice, cerebral
calcifications
Dx: serum anti-CMV
IgM, intranuclear
inclusions “owl eyes”
in renal tubular cells
on UA
Syphilis
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Treponema pallidum
crosses placenta
Often fatal
Hutchinson’s Triad: abnormal central incisors,
interstitial keratitis, profound SNHL
 Dx: VDRL, FTA-ABS, audiogram
 Tx: long term PCN, ampicillin, tetracycline or
erythromycin; steroids for HL
Prenatal Teratogens
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EtOH
Thalidomide
Radiation
Aminoglycosides
Perinatal Causes of HL
 Hypoxia
 Kernicterus
 Persistent fetal circulation
Postnatal Causes of HL
 Meningitis (suppurative labryrinthitis)
 Ossification of labryinth
 Steroids help prevent HL
 Most common postnatal cause of HL
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Viral infection: mumps
Ototoxins/Chemotherapy
Trauma (acoustic, blunt, penetrating)
Perilymph fistula
Neoplasm: medulloblastoma, AN, fibrous
dysplasia, histiocytosis)
 Autoimmune (rare in children)
Inner Ear Dysmorphologies
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Michel’s aplasia
Mondini aplasia
Scheibe aplasia
Alexander aplasia
Bing Siebenmann
Enlarged vestibular aqueduct
Absence of CN VIII
Michel’s aplasia
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AD or thalidomide exposure
Complete aplasia of inner ear
Anacusis, normal middle and outer ear
Dx: CT shows hypoplastic petrous pyramid,
absent cochlea and labyrinth
Mondini Aplasia
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AD
Most common cochlear abnormality
Progressive or fluctuating HL
 risk of perilymphatic gusher and
meningitis from dilated cochlear aqueduct
 Dx: CT reveals single turned cochlea, no
interscalar septum
 Tx: HA, cochlear implant
Schiebe Aplasia
 AR
 Partial or complete aplasia of pars inferior
(cochlea and saccule), normal pars superior
(SCC and utricle)
 Defect of membranous labyrinth only,
therefore can not diagnose on CT
Alexander Aplasia
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AR
Abnormal cochlear duct/ basal turn
High frequency SNHL
Cannot diagnose on CT
Enlarged vestibular aqueduct
 Defined by diameter of duct >2mm at
midpoint
 Progressive cochleovestibular loss
 No treatment
Thanks for listening!
Questions
 What % of patients with NF-1 have
acoustic neuromas?
a)
b)
c)
d)
5%
20%
50%
95%
 What % of patients with NF-2 have acoustic
neuromas?
a) 5%
b) 20%
c) 50%
d) 95%
 What is the basic defect that causes Alport
syndrome?
a) abnormal renal tubules
b) abnormal collagen IV in glomerulus
c) abnormal collagen I in glomerulus
d) abnormal renal arteries
 What is the primary inheritance pattern for
Alport’s syndrome?
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What syndrome does
this patient have?
a)
b)
c)
d)
Goldenhar
Treacher Collins
Crouzon
Apert
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What inner ear aplasia will not allow for
cochlear implants or amplification aids?
a)
b)
c)
d)
Mondini aplasia
Michel’s aplasia
Enlarged vestibular aqueduct
Alexander aplasia
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Which inner ear dyplasia is characterized
by a lack of septae in the cochlea and only
a basal turn?
a)
b)
c)
d)
Mondini aplasia
Michel’s aplasia
Enlarged vestibular aqueduct
Alexander aplasia
 What is the inheritance pattern of MIDD
and MELAS?
 What abnormality is noted on this temporal bone
CT?
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What genetic mutation is responsible for
type I and III Waardenburg syndrome?
a)
b)
c)
d)
COL2A1
Pendrin
PAX3
Chr 22q12
Thanks for listening!