Congenital Hearing Loss

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

2. Etiology • Congenital HL • 50% Genetic • 50% Acquired • Childhood Onset HL • 50% Genetic • 25% Acquired • 25% Unknown

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

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

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

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

7. 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

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

9. Usher

10. 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

11. 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).

12. 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

13. 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

14. Goldenhar Syndrome

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

16. AD Syndromes • Waardenburg • Treacher Collins • Apert • Crouzon • Stickler • Neurofibromatosis • Brancio-oto-renal

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

18. 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

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

20. 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

21. Treacher Collins

22. 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

23. Apert

24. 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

25. Crouzon

26. 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

27. 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)

28. NF-1

29. 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%

30. X-linked Disorders • Alport’s syndrome • Otopalatal-digital • Norrie syndrome

31. Alport’s Syndrome • X-linked 80%, autosomal dominant 20% • Progressive glomerulonephritis and SNHL • Abnormal type IV collagen in GBM; gene COL4A5

32. Alport’s Syndrome • Bilateral degeneration of organ of Corti and stria vascularis • Ocular disorders (myopia, cataracts) • Dx: UA, BUN, Cr • Tx: dialysis, renal transplant

33. Otopalatal-digital • Ossicular malformation (CHL) • Palate defects • Digital abnormalities: broad fingers and toes • Hypertelorism, short stature, mental retardation

34. Otopalatal-digital

35. Norrie Syndrome • Blindness • Progressive mental retardation • Hearing loss

36. 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

37. Acquired Congenital HL • Prenatal: infections, teratogens • Perinatal: NICU admission • Postnatal: infections, neoplasms

38. Prenatal Infections • TORCHS: • Toxoplasmosis • Rubella • CMV • HSV encephalitis • Syphilis

39. 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

40. 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

41. 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

42. Prenatal Teratogens • EtOH • Thalidomide • Radiation • Aminoglycosides

43. Perinatal Causes of HL • Hypoxia • Kernicterus • Persistent fetal circulation

44. 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)

45. Inner Ear Dysmorphologies • Michel’s aplasia • Mondini aplasia • Scheibe aplasia • Alexander aplasia • Bing Siebenmann • Enlarged vestibular aqueduct • Absence of CN VIII

46. 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

47. Mondini 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

49. 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

50. Alexander Aplasia • AR • Abnormal cochlear duct/ basal turn • High frequency SNHL • Cannot diagnose on CT