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     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)

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 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

  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

    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

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

AD Syndromes

       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)

       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

       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:     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

Otopalatal digital

Norrie Syndrome

   Blindness Progressive mental retardation Hearing loss

Mitochondrial 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

Acquired Congenital HL

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

Prenatal Infections

 TORCHS:   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

    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

    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 Viral infection: mumps Ototoxins/Chemotherapy Trauma (acoustic, blunt, penetrating) Perilymph fistula Neoplasm: medulloblastoma, AN, fibrous dysplasia, histiocytosis) Autoimmune (rare in children)

Inner Ear Dysmorphologies

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

Michel’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

Mondini Aplasia

  AD Most common cochlear abnormality    risk of perilymphatic gusher and meningitis from dilated cochlear aqueduct  Progressive or fluctuating HL 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

    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) 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 primary inheritance pattern for Alport’s syndrome?

 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

 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 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

Thanks for listening!