Congenital Hearing LossCongenital Hearing Loss

Ashley Starkweather, MD

UCLA Head and Neck Surgery

February 25, 2009

Ashley Starkweather, MD

UCLA Head and Neck Surgery

February 25, 2009

EtiologyEtiology

Congenital HL 50% Genetic 50% Acquired

Childhood Onset HL 50% Genetic 25% Acquired 25% Unknown

Congenital HL 50% Genetic 50% Acquired

Childhood Onset HL 50% Genetic 25% Acquired 25% Unknown

Genetic HLGenetic HL

75% non-syndromal 25% syndromal

75% autosomal recessive (AR) 25% autosomal dominant (AD) 1-2% X-linked Rare mitochondrial

75% non-syndromal 25% syndromal

75% autosomal recessive (AR) 25% autosomal dominant (AD) 1-2% X-linked Rare mitochondrial

Autosomal recessive HLAutosomal recessive HL

Monogenic, 25% risk to offspring if both parents are carriers

Severe to profound SNHL, prelingual onset

Monogenic, 25% risk to offspring if both parents are carriers

Severe to profound SNHL, prelingual onset

Autosomal recessive syndromal HL

Autosomal recessive syndromal HL

Usher syndrome Pendred Jervel and Lange Nielsen Goldenhar (Oculoauriculoverterbral

spectrum)

Usher syndrome Pendred Jervel and Lange Nielsen Goldenhar (Oculoauriculoverterbral

spectrum)

Usher SyndromeUsher Syndrome

Retinitis pimentosa and SNHL Night blindness > field cut > central

blindness Most common cause of congenital deafness Dx: electroretinography

Retinitis pimentosa and SNHL Night blindness > field cut > central

blindness Most common cause of congenital deafness Dx: electroretinography

Usher TypesUsher 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

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 TypesUsher Types

Type III: Progressive SNHL and vestibular dysfunction Vestibulocerebellar ataxia

Type IV: Mental retardation and hypotonia

Type III: Progressive SNHL and vestibular dysfunction Vestibulocerebellar ataxia

Type IV: Mental retardation and hypotonia

Usher Usher

Pendred SyndromePendred 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

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 47-year-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).

Transverse CT scans of the middle ear in a 47-year-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 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

Congenital profound SNHL Prolonged QT interval with syncope,

sudden death Gene mutation: KVKQT1 = abnormal K+

channel Dx: EKG Tx: Beta blockers, hearing aids

Goldenhar SyndromeGoldenhar Syndrome

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

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 SyndromeGoldenhar Syndrome

Autosomal Dominant Autosomal Dominant

Vertical pattern of inheritance Risk to offspring of 50% if 1 parent

affected Variable penetrance and expressivity Often postlingual hearing loss, progressive

Vertical pattern of inheritance Risk to offspring of 50% if 1 parent

affected Variable penetrance and expressivity Often postlingual hearing loss, progressive

AD SyndromesAD Syndromes

Waardenburg Treacher Collins Apert Crouzon Stickler Neurofibromatosis Brancio-oto-renal

Waardenburg Treacher Collins Apert Crouzon Stickler Neurofibromatosis Brancio-oto-renal

Waardenburg SyndromeWaardenburg Syndrome

Abnormal tyrosine metabolism

Pigment abnormalities: heterochromic iriditis, white forelock, patchy skin depigmentation

Craniofacial abnormalities: dystopia canthorum, synophrys, flat nasal root

Abnormal tyrosine metabolism

Pigment abnormalities: heterochromic iriditis, white forelock, patchy skin depigmentation

Craniofacial abnormalities: dystopia canthorum, synophrys, flat nasal root

Waardenburg TypesWaardenburg 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

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 TypesWaardenburg Types

Type III (most severe): Unilateral ptosis and skeletal abnormalities PAX3 mutation

Type IV: Type II plus Hirschsprung’s disease

(aganglionic megacolon)

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)

Treacher Collins (Mandibulofacial dysostosis)

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

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 CollinsTreacher Collins

Apert Syndrome(Acrocephalosyndactyly)

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

Middle and inner ear affected Stapes fixation (CHL), patent cochlear

aqueduct, large subarcuate fossa Hand syndactyly, midface abnormalities,

craniofacial dysostosis, trapezoid mouth

ApertApert

Crouzon Syndrome(craniofacial dysostosis)

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

Atresia and stenosis of EAC, CHL, ossicular deformities

Cranial synostosis, small maxilla, exophthalmos, parrot nose, short upper lip, mandibular prognathism, hypertelorism

Abnormal FGF receptors

CrouzonCrouzon

Stickler SyndromeStickler Syndrome

Progressive Arthro-Ophthalmopathy Progressive SNHL (80%) Marfanoid body habitus Severe myopia, retinal detachment Flat midface Hypermobile joints Pierre Robin sequence: micrognathia,

glossoptosis, cleft palate

Progressive Arthro-Ophthalmopathy Progressive SNHL (80%) Marfanoid body habitus Severe myopia, retinal detachment Flat midface Hypermobile joints Pierre Robin sequence: micrognathia,

glossoptosis, cleft palate

NeurofibromatosisNeurofibromatosis

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 (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-1NF-1

Branchio-oto-renal (Melnick Fraser Syndrome)

Branchio-oto-renal (Melnick Fraser Syndrome)

Renal abnormalities: mild hypoplasia to bilateral aplasia

Branchial cleft cyts Preauricular pits EYA1 on Chr 8q13 Hearing loss:

Penetrance: 80% Mixed: 50% Conductive: 30% SNHL: 20%

Renal abnormalities: mild hypoplasia to bilateral aplasia

Branchial cleft cyts Preauricular pits EYA1 on Chr 8q13 Hearing loss:

Penetrance: 80% Mixed: 50% Conductive: 30% SNHL: 20%

X-linked DisordersX-linked Disorders

Alport’s syndrome Otopalatal-digital Norrie syndrome

Alport’s syndrome Otopalatal-digital Norrie syndrome

Alport’s SyndromeAlport’s Syndrome

X-linked 80%, autosomal dominant 20%

Progressive glomerulonephritis and SNHL

Abnormal type IV collagen in GBM; gene COL4A5

X-linked 80%, autosomal dominant 20%

Progressive glomerulonephritis and SNHL

Abnormal type IV collagen in GBM; gene COL4A5

Alport’s SyndromeAlport’s Syndrome

Bilateral degeneration of organ of Corti and stria vascularis

Ocular disorders (myopia, cataracts) Dx: UA, BUN, Cr Tx: dialysis, renal transplant

Bilateral degeneration of organ of Corti and stria vascularis

Ocular disorders (myopia, cataracts) Dx: UA, BUN, Cr Tx: dialysis, renal transplant

Otopalatal-digitalOtopalatal-digital

Ossicular malformation (CHL) Palate defects Digital abnormalities: broad fingers and

toes Hypertelorism, short stature, mental

retardation

Ossicular malformation (CHL) Palate defects Digital abnormalities: broad fingers and

toes Hypertelorism, short stature, mental

retardation

Otopalatal-digital

Otopalatal-digital

Norrie SyndromeNorrie Syndrome

Blindness Progressive mental retardation Hearing loss

Blindness Progressive mental retardation Hearing loss

Mitochondrial DisordersMitochondrial Disorders

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

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 HLAcquired Congenital HL

Prenatal: infections, teratogens Perinatal: NICU admission Postnatal: infections, neoplasms

Prenatal: infections, teratogens Perinatal: NICU admission Postnatal: infections, neoplasms

Prenatal InfectionsPrenatal Infections

TORCHS: Toxoplasmosis Rubella CMV HSV encephalitis Syphilis

TORCHS: Toxoplasmosis Rubella CMV HSV encephalitis Syphilis

RubellaRubellaCataracts, 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

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

CMVCMV 1-2% of live births Only 10% have HL Hemolytic anemia, microcephaly, mental

retardation, HSM, jaundice, cerebral calcifications

1-2% of live births Only 10% have HL Hemolytic anemia, microcephaly, mental

retardation, HSM, jaundice, cerebral calcifications

Dx: serum anti-CMV Dx: serum anti-CMV IgM, intranuclear IgM, intranuclear inclusions “owl eyes” inclusions “owl eyes” in renal tubular cells in renal tubular cells on UAon UA

SyphilisSyphilis

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

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 TeratogensPrenatal Teratogens

EtOH Thalidomide Radiation Aminoglycosides

EtOH Thalidomide Radiation Aminoglycosides

Perinatal Causes of HLPerinatal Causes of HL

Hypoxia Kernicterus Persistent fetal circulation

Hypoxia Kernicterus Persistent fetal circulation

Postnatal Causes of HLPostnatal Causes of HL Meningitis (suppurative labryrinthitis)

Ossification of labryinth Steroids help prevent HL Most common postnatal cause of HL

Viral infection: mumps Ototoxins/Chemotherapy Trauma (acoustic, blunt, penetrating) Perilymph fistula Neoplasm: medulloblastoma, AN, fibrous dysplasia,

histiocytosis) Autoimmune (rare in children)

Meningitis (suppurative labryrinthitis) Ossification of labryinth Steroids help prevent HL Most common postnatal cause of HL

Viral infection: mumps Ototoxins/Chemotherapy Trauma (acoustic, blunt, penetrating) Perilymph fistula Neoplasm: medulloblastoma, AN, fibrous dysplasia,

histiocytosis) Autoimmune (rare in children)

Inner Ear DysmorphologiesInner Ear Dysmorphologies

Michel’s aplasia Mondini aplasia Scheibe aplasia Alexander aplasia Bing Siebenmann Enlarged vestibular aqueduct Absence of CN VIII

Michel’s aplasia Mondini aplasia Scheibe aplasia Alexander aplasia Bing Siebenmann Enlarged vestibular aqueduct Absence of CN VIII

Michel’s aplasiaMichel’s aplasia

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

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 AplasiaMondini Aplasia

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

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 AplasiaSchiebe 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

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 AplasiaAlexander Aplasia

AR Abnormal cochlear duct/ basal turn High frequency SNHL Cannot diagnose on CT

AR Abnormal cochlear duct/ basal turn High frequency SNHL Cannot diagnose on CT

Enlarged vestibular aqueductEnlarged vestibular aqueduct

Defined by diameter of duct >2mm at midpoint

Progressive cochleovestibular loss No treatment

Defined by diameter of duct >2mm at midpoint

Progressive cochleovestibular loss No treatment

Thanks for listening!Thanks for listening!

QuestionsQuestions

What % of patients with NF-1 have acoustic neuromas?a) 5%

b) 20%

c) 50%

d) 95%

What % of patients with NF-1 have acoustic neuromas?a) 5%

b) 20%

c) 50%

d) 95%

What % of patients with NF-2 have acoustic neuromas?a) 5%

b) 20%

c) 50%

d) 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 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?

What is the primary inheritance pattern for Alport’s syndrome?

What syndrome does this patient have?

a) Goldenhar

b) Treacher Collins

c) Crouzon

d) Apert

What syndrome does this patient have?

a) Goldenhar

b) Treacher Collins

c) Crouzon

d) Apert

What inner ear aplasia will not allow for cochlear implants or amplification aids?

a) Mondini aplasia

b) Michel’s aplasia

c) Enlarged vestibular aqueduct

d) Alexander aplasia

What inner ear aplasia will not allow for cochlear implants or amplification aids?

a) Mondini aplasia

b) Michel’s aplasia

c) Enlarged vestibular aqueduct

d) Alexander aplasia

Which inner ear dyplasia is characterized by a lack of septae in the cochlea and only a basal turn?

a) Mondini aplasia

b) Michel’s aplasia

c) Enlarged vestibular aqueduct

d) Alexander aplasia

Which inner ear dyplasia is characterized by a lack of septae in the cochlea and only a basal turn?

a) Mondini aplasia

b) Michel’s aplasia

c) Enlarged vestibular aqueduct

d) Alexander aplasia

What is the inheritance pattern of MIDD and MELAS?

What is the inheritance pattern of MIDD and MELAS?

What abnormality is noted on this temporal bone CT?

What abnormality is noted on this temporal bone CT?

What genetic mutation is responsible for type I and III Waardenburg syndrome?

a) COL2A1

b) Pendrin

c) PAX3

d) Chr 22q12

What genetic mutation is responsible for type I and III Waardenburg syndrome?

a) COL2A1

b) Pendrin

c) PAX3

d) Chr 22q12

Thanks for listening!Thanks for listening!