Congenital Hearing Loss Congenital Hearing Loss Ashley - PowerPoint PPT Presentation

Congenital Hearing Loss Congenital Hearing Loss Ashley Starkweather, MD Ashley Starkweather, MD UCLA Head and Neck Surgery UCLA Head and Neck Surgery February 25, 2009 February 25, 2009

Etiology Etiology � Congenital HL � Congenital HL � 50% Genetic � 50% Genetic � 50% Acquired � 50% Acquired � Childhood Onset HL � Childhood Onset HL � 50% Genetic � 50% Genetic � 25% Acquired � 25% Acquired � 25% Unknown � 25% Unknown

Genetic HL Genetic HL � 75% non-syndromal � 75% non-syndromal � 25% syndromal � 25% syndromal � 75% autosomal recessive (AR) � 75% autosomal recessive (AR) � 25% autosomal dominant (AD) � 25% autosomal dominant (AD) � 1-2% X-linked � 1-2% X-linked � Rare mitochondrial � Rare mitochondrial

Autosomal recessive HL Autosomal recessive HL � Monogenic, 25% � Monogenic, 25% risk to offspring if risk to offspring if both parents are both parents are carriers carriers � Severe to � Severe to profound SNHL, profound SNHL, prelingual onset prelingual onset

Autosomal recessive syndromal Autosomal recessive syndromal HL HL � Usher syndrome � Usher syndrome � Pendred � Pendred � Jervel and Lange Nielsen � Jervel and Lange Nielsen � Goldenhar (Oculoauriculoverterbral � Goldenhar (Oculoauriculoverterbral spectrum) spectrum)

Usher Syndrome Usher Syndrome � Retinitis pimentosa and SNHL � Retinitis pimentosa and SNHL � Night blindness > field cut > central � Night blindness > field cut > central blindness blindness � Most common cause of congenital deafness � Most common cause of congenital deafness � Dx: electroretinography � Dx: electroretinography

Usher Types Usher Types � Type I (most common): � Type I (most common): � Profound SNHL, no vestibular fxn � Profound SNHL, no vestibular fxn � RP onset in early childhood � RP onset in early childhood � Atypical myosin (myosin 7A): interferes with � Atypical myosin (myosin 7A): interferes with mechanoelectrical transduction in labyrinthine hair cells mechanoelectrical transduction in labyrinthine hair cells � Type II: � Type II: � Congenital sloping SNHL � Congenital sloping SNHL � Normal vestibular fxn � Normal vestibular fxn � RP onset in teens � RP onset in teens

Usher Types Usher Types � Type III: � Type III: � Progressive SNHL and vestibular dysfunction � Progressive SNHL and vestibular dysfunction � Vestibulocerebellar ataxia � Vestibulocerebellar ataxia � Type IV: � Type IV: � Mental retardation and hypotonia � Mental retardation and hypotonia

Usher Usher

Pendred Syndrome Pendred Syndrome � Defect in tyrosine iodination � Defect in tyrosine iodination � Gene mutation: affects pendrin, molecule involved � Gene mutation: affects pendrin, molecule involved in chloride-iodine transport in chloride-iodine transport � Sx: severe to profound SNHL, multinodular goiter � Sx: severe to profound SNHL, multinodular goiter in childhood in childhood � Assoc with Mondini malformation and enlarged � Assoc with Mondini malformation and enlarged vestibular aqueduct vestibular aqueduct � Dx: (+) perchlorate test � Dx: (+) perchlorate test � Tx: thyroid hormone to suppress goiter � Tx: thyroid hormone to suppress goiter

� Transverse CT scans of � Transverse CT scans of the middle ear in a 47- the middle ear in a 47- year-old patient with year-old patient with Pendred syndrome. Pendred syndrome. � (a) Modiolus is not � (a) Modiolus is not discernible (short arrow). discernible (short arrow). Vestibular aqueduct Vestibular aqueduct (arrowheads) and (arrowheads) and vestibule (long arrow) are vestibule (long arrow) are enlarged. enlarged. � (b) Interscalar septum � (b) Interscalar septum between upper and middle between upper and middle turn of the cochlea is turn of the cochlea is absent (arrow). absent (arrow).

Jervell and Lange Nielsen Jervell and Lange Nielsen � Congenital profound SNHL � Congenital profound SNHL � Prolonged QT interval with syncope, � Prolonged QT interval with syncope, sudden death sudden death � Gene mutation: KVKQT1 = abnormal K+ � Gene mutation: KVKQT1 = abnormal K+ channel channel � Dx: EKG � Dx: EKG � Tx: Beta blockers, hearing aids � Tx: Beta blockers, hearing aids

Goldenhar Syndrome Goldenhar Syndrome � First and second arch derivatives, hemifacial � First and second arch derivatives, hemifacial � CHL and SNHL (mixed) � CHL and SNHL (mixed) � Ocular: epibulbar dermoids, colobomas � Ocular: epibulbar dermoids, colobomas � Auricular: preauricular appendages, pinna � Auricular: preauricular appendages, pinna abnormalities, EAC atresia, ossicular abnormalities, EAC atresia, ossicular malformation/absence, abnormal facial nerve, malformation/absence, abnormal facial nerve, stapedius, semicircular canals and oval window stapedius, semicircular canals and oval window � Vertebral: fusion/absence of cervical vertebrae � Vertebral: fusion/absence of cervical vertebrae

Goldenhar Syndrome Goldenhar Syndrome

Autosomal Dominant Autosomal Dominant � Vertical pattern of inheritance � Vertical pattern of inheritance � Risk to offspring of 50% if 1 parent affected � Risk to offspring of 50% if 1 parent affected � Variable penetrance and expressivity � Variable penetrance and expressivity � Often postlingual hearing loss, progressive � Often postlingual hearing loss, progressive

AD Syndromes AD Syndromes � Waardenburg � Waardenburg � Treacher Collins � Treacher Collins � Apert � Apert � Crouzon � Crouzon � Stickler � Stickler � Neurofibromatosis � Neurofibromatosis � Brancio-oto-renal � Brancio-oto-renal

Waardenburg Syndrome Waardenburg Syndrome � Abnormal tyrosine � Abnormal tyrosine metabolism metabolism � Pigment abnormalities: � Pigment abnormalities: heterochromic iriditis, heterochromic iriditis, white forelock, patchy white forelock, patchy skin depigmentation skin depigmentation � Craniofacial � Craniofacial abnormalities: dystopia abnormalities: dystopia canthorum, synophrys, canthorum, synophrys, flat nasal root flat nasal root

Waardenburg Types Waardenburg Types � Type I: � Type I: � Dystopia canthorum, pigment and craniofacial � Dystopia canthorum, pigment and craniofacial abnormalities, 20% with SNHL abnormalities, 20% with SNHL � Mutation in PAX3 gene � Mutation in PAX3 gene � Type II: � Type II: � No dystopia canthorum, 50% with SNHL but � No dystopia canthorum, 50% with SNHL but not as severe not as severe � MITF mutation � MITF mutation

Waardenburg Types Waardenburg Types � Type III (most severe): � Type III (most severe): � Unilateral ptosis and skeletal abnormalities � Unilateral ptosis and skeletal abnormalities � PAX3 mutation � PAX3 mutation � Type IV: � Type IV: � Type II plus Hirschsprung’s disease � Type II plus Hirschsprung’s disease (aganglionic megacolon) (aganglionic megacolon)

Treacher Collins Treacher Collins (Mandibulofacial dysostosis) (Mandibulofacial dysostosis) � Hypoplasia of mandible and facial bones � Hypoplasia of mandible and facial bones � Downsloping palpebral fissures, colobomas � Downsloping palpebral fissures, colobomas � Atretic external and middle ear � Atretic external and middle ear � Mixed HL � Mixed HL � Cleft palate (35%) � Cleft palate (35%) � Gene mutation on chr 5q: TCOF1 codes for a cell � Gene mutation on chr 5q: TCOF1 codes for a cell transport protein (treacle) transport protein (treacle) � Tx: BAHA, bone conduction HA, surgical � Tx: BAHA, bone conduction HA, surgical correction of aural atresia correction of aural atresia

Treacher Collins Treacher Collins

Apert Syndrome Apert Syndrome (Acrocephalosyndactyly) (Acrocephalosyndactyly) � Middle and inner ear affected � Middle and inner ear affected � Stapes fixation (CHL), patent cochlear � Stapes fixation (CHL), patent cochlear aqueduct, large subarcuate fossa aqueduct, large subarcuate fossa � Hand syndactyly, midface abnormalities, � Hand syndactyly, midface abnormalities, craniofacial dysostosis, trapezoid mouth craniofacial dysostosis, trapezoid mouth

Apert Apert

Crouzon Syndrome Crouzon Syndrome (craniofacial dysostosis) (craniofacial dysostosis) � Atresia and stenosis of EAC, CHL, � Atresia and stenosis of EAC, CHL, ossicular deformities ossicular deformities � Cranial synostosis, small maxilla, � Cranial synostosis, small maxilla, exophthalmos, parrot nose, short upper lip, exophthalmos, parrot nose, short upper lip, mandibular prognathism, hypertelorism mandibular prognathism, hypertelorism � Abnormal FGF receptors � Abnormal FGF receptors

Crouzon Crouzon

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