Hereditary Hearing Loss

UCI Otolaryngology UCI Otolaryngology Head and Neck SurgeryHead and Neck Surgery

Thursday Morning ConferenceThursday Morning Conference

November 10, 2005November 10, 2005

Paul K. Holden, MDPaul K. Holden, MD

Patient ConferencePatient Conference

3 yo male presents to clinic as new patient 3 yo male presents to clinic as new patient referred by audiologist for hearing loss.referred by audiologist for hearing loss.


Mother has noted pt does not seem to Mother has noted pt does not seem to respond to normal voice, watches TV respond to normal voice, watches TV loudly and does not speak except for the loudly and does not speak except for the words “agua” and “mama”words “agua” and “mama”

No h/o trauma, illness, hospitalizationNo h/o trauma, illness, hospitalization No medicationsNo medications Normal delivery (40 weeks) no events, Normal delivery (40 weeks) no events,

mother unaware of hearing test at time of mother unaware of hearing test at time of birth.birth.


FH – Father has some hearing loss of FH – Father has some hearing loss of unknown type, some uncles/cousins with unknown type, some uncles/cousins with hearing loss. Two siblings both with hearing loss. Two siblings both with normal hearing, one older sister has DD normal hearing, one older sister has DD and wears glasses. and wears glasses.

Soc Hx – All other family members born in Soc Hx – All other family members born in Mexico, pt born in US. Lives w/ 2 sisters Mexico, pt born in US. Lives w/ 2 sisters and both parents in apartment.and both parents in apartment.

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PExPEx WDWN, nonverbal, not following commandsWDWN, nonverbal, not following commands Brow Hirsuitism, normocephalicBrow Hirsuitism, normocephalic PERRL, EOM grossly intact, broad nasal root with PERRL, EOM grossly intact, broad nasal root with

increased intercanthal distance, very pale blue eyesincreased intercanthal distance, very pale blue eyes TM c/i/m AUTM c/i/m AU Nose clear, MMMNose clear, MMM OC clear, MMM, 1+ tonsilsOC clear, MMM, 1+ tonsils Neck supple, no LAD, trach ML, no thyromegalyNeck supple, no LAD, trach ML, no thyromegaly


WAARDENBURG SYNDROME

Hereditary Hearing LossHereditary Hearing Loss


DEFINITIONDEFINITION – HL present at birth or – HL present at birth or develops any time thereafter and is develops any time thereafter and is believed to have a genetic cause. believed to have a genetic cause.


WHAT IT AIN’TWHAT IT AIN’T ““Congenital” which is a general term for HL Congenital” which is a general term for HL

present at birthpresent at birth Acquired Prenatal Hearing Loss (Syphilis, Acquired Prenatal Hearing Loss (Syphilis,

Rubella, CMV, Toxic Exposure)Rubella, CMV, Toxic Exposure) Other HL (congenital cholesteatoma, Other HL (congenital cholesteatoma,

otosclerosis, sudden SNHL)otosclerosis, sudden SNHL)


Workup:Workup: Hx incl CV, Neuro, Rheum, Endo, Renal, Hx incl CV, Neuro, Rheum, Endo, Renal,

Ophtho, past ototoxic exp, infxns, vertigo, Ophtho, past ototoxic exp, infxns, vertigo, Px – Abnormal Facies, infxn, cholesteatomaPx – Abnormal Facies, infxn, cholesteatoma Surg/Trauma HxSurg/Trauma Hx MedsMeds FHx incl CV, Neuro, Rheum, Endo, Renal, FHx incl CV, Neuro, Rheum, Endo, Renal,

Ophtho. Pedigree if genetic dz suspected.Ophtho. Pedigree if genetic dz suspected.


Workup:Workup: Audio / ABR, SRT, Tympanometry, OAE, Audio / ABR, SRT, Tympanometry, OAE,

repeat audio q3-6morepeat audio q3-6mo ENG when asymmetric SNHL of unk etiolENG when asymmetric SNHL of unk etiol Labs – Treponemal, Thyroid Panel, UALabs – Treponemal, Thyroid Panel, UA EKGEKG T-Bone CT (non-con)T-Bone CT (non-con) Ophtho Eval if Visual Hx or FHxOphtho Eval if Visual Hx or FHx


ClassificationClassification Associated AnomaliesAssociated Anomalies

SyndromicSyndromic Non-SyndromicNon-Syndromic

Developmental OnsetDevelopmental Onset PrelingualPrelingual PostlingualPostlingual


Genetic ClassificationGenetic Classification Autosomal DominantAutosomal Dominant Autosomal RecessiveAutosomal Recessive X-LinkedX-Linked MitochondrialMitochondrial


AD SyndromicAD Syndromic Branchio-Oto-Renal – Branchio-Oto-Renal – Outer/Middle/Inner Ear Anomalies Outer/Middle/Inner Ear Anomalies

(preauricular pits common, microtia, etc), Lateral cervical sinus/cyst/cleft, (preauricular pits common, microtia, etc), Lateral cervical sinus/cyst/cleft, Renal agenesis/dysplasia, HL (90%) is SN/C or Mixed prelingualRenal agenesis/dysplasia, HL (90%) is SN/C or Mixed prelingual

NF-II –NF-II – Bilat Schwannomas, meningiomas, gliomas, Bilat Schwannomas, meningiomas, gliomas, cataracts/lenticular opacities, HL is retrocochlear and usually postlingual - cataracts/lenticular opacities, HL is retrocochlear and usually postlingual - MERLIN geneMERLIN gene

Stickler – Stickler – congenital vitreous anomaly AND any 3 of: myopia before congenital vitreous anomaly AND any 3 of: myopia before age 6, retinal detachment/lattice degen, joint hypermobility, SNHL, midline age 6, retinal detachment/lattice degen, joint hypermobility, SNHL, midline cleft (may be sumucous). May have Robin Seq, HL may be mixed pre/post cleft (may be sumucous). May have Robin Seq, HL may be mixed pre/post lingual, 50% blind by adolescence, marfanoid habituslingual, 50% blind by adolescence, marfanoid habitus


AD Syndromic (cont’d)AD Syndromic (cont’d) Waardenburg – Waardenburg – Four types: Four types: Type IType I = SNHL, White Forelock, = SNHL, White Forelock,

heterochromia/hopoplastic blue eyes, dystopia canthorum. Can also have heterochromia/hopoplastic blue eyes, dystopia canthorum. Can also have synophrys, broad nasal root, alar hypoplasia. synophrys, broad nasal root, alar hypoplasia. Type 2Type 2 = no dystopia = no dystopia canthorum. canthorum. Type 3Type 3 = Type 1 + upper limb contracture. = Type 1 + upper limb contracture. Type 4Type 4 = incld = incld Hirschprung. For all types, HL is prelingual.Hirschprung. For all types, HL is prelingual.

Treacher Collins – Treacher Collins – 11stst branchial arch abnormalities of midface branchial arch abnormalities of midface hypoplasia, micrognathia, macrostomia, colobomas of lower lids, hypoplasia, micrognathia, macrostomia, colobomas of lower lids, downward palpebral fissures, Cleft Palate, CHL (EE/ME anomalies).downward palpebral fissures, Cleft Palate, CHL (EE/ME anomalies).

Crouzon – Crouzon – craniosynostosis, hypertelorism, midface hypoplasia, craniosynostosis, hypertelorism, midface hypoplasia, exophthalmos. 1/3 CHL due to EE/ME anomalies.exophthalmos. 1/3 CHL due to EE/ME anomalies.


AR SyndromicAR Syndromic Jervell Lange-Nielsen – Jervell Lange-Nielsen – Profound prelingual SNHL, Profound prelingual SNHL,

syncope, sudden death (prolonged QT). Syncope w/ exertion or emotion. syncope, sudden death (prolonged QT). Syncope w/ exertion or emotion. High mortality rate sig reduced w/ Dx and Tx.High mortality rate sig reduced w/ Dx and Tx.

Pendred – Pendred – Prelingual (usu profound) SNHL and Goiter. T-bone Prelingual (usu profound) SNHL and Goiter. T-bone abnormalities (Mondini, DVA). Goiter may develop later in childhood but abnormalities (Mondini, DVA). Goiter may develop later in childhood but usually euthyroid.usually euthyroid.

Usher – Usher – Most common AR syndromic HL, has prelingual SNHL plus Most common AR syndromic HL, has prelingual SNHL plus retinitis pigmentosa. ½ of all Deaf-Blinds in US. 3 Types: USH1 – includes retinitis pigmentosa. ½ of all Deaf-Blinds in US. 3 Types: USH1 – includes vestibular areflexia (no caloric response) and profound HL, USH2 – nl vestibular areflexia (no caloric response) and profound HL, USH2 – nl vestibular fct and use HA, USH3 – progressive HL and vestibular probs. In vestibular fct and use HA, USH3 – progressive HL and vestibular probs. In all 3, RP is progressive, starting w/ nyctaltopia (night blindness). all 3, RP is progressive, starting w/ nyctaltopia (night blindness). Electroretinography (ERG) for early RP dx.Electroretinography (ERG) for early RP dx.


X-Linked SyndromicX-Linked Syndromic Alport – Alport – SNHL (hi freq), progressive glomerulonephritis, anterior SNHL (hi freq), progressive glomerulonephritis, anterior

lenticonus, white macular flecks (or both). Screen hematuria/proteinuria lenticonus, white macular flecks (or both). Screen hematuria/proteinuria (multiple specimens) usually found age 3-4 yrs, esp after URI. (multiple specimens) usually found age 3-4 yrs, esp after URI.


Michondrial SyndromicMichondrial Syndromic Kearns-Sayre – Kearns-Sayre – Eye, CV, Ataxic, Mixed HLEye, CV, Ataxic, Mixed HL

Maternal Diabetes+Deafness – Maternal Diabetes+Deafness – SNHLSNHL

MELAS - MELAS - (Mito encephalopathy, Lactic Acidosis, Stroke-Like (Mito encephalopathy, Lactic Acidosis, Stroke-Like Episodes) 30% HLEpisodes) 30% HL

MERRF – MERRF – (Myoclonic Epilepsy and Ragged Red Fibers) incl ataxia, (Myoclonic Epilepsy and Ragged Red Fibers) incl ataxia,

dementia, optic atrophy and variable SNHLdementia, optic atrophy and variable SNHL..


NonSyndromicNonSyndromic AD – AD – 18% of nonsyndromic HL, postlingual, progressive and milder. 18% of nonsyndromic HL, postlingual, progressive and milder.

>70 loci.>70 loci.

AR – AR – 88% of nonsyndromic HL, more severe, prelingual,88% of nonsyndromic HL, more severe, prelingual, DFNb-1 DFNb-1 CConnexinonnexin

X-linked – X-linked – <2%, can have dev delay, stapes fixation, dilation of <2%, can have dev delay, stapes fixation, dilation of vestibule (risk if perilymph gusher)vestibule (risk if perilymph gusher)

Mitochondrial – Mitochondrial – elevated sensitivity to aminoglycosides.elevated sensitivity to aminoglycosides.


TreatmentTreatment Consults – Consults – Geneticist, Ophtho, Renal, Endocrine, Geneticist, Ophtho, Renal, Endocrine,

Cardiology, Neuro, CraniofacialCardiology, Neuro, Craniofacial

Hearing - Hearing - HAs, Reconstruction/Prostheses, BAHA, CIHAs, Reconstruction/Prostheses, BAHA, CI

Avoid loud noises, noisy environmentsAvoid loud noises, noisy environments Regular Audio F/URegular Audio F/U


Pendred Syndrome


Treacher Collins Syndrome


Branchio-Oto-Renal Syndrome


Crouzon Syndrome


Waardenburg Syndrome



Stickler Syndrome

THANK YOU!

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Hereditary Hearing Loss