Syndromes and Disorders Masterlist

What is BOR?

Branchio-Oto-Renal

a genetic disorder causing malformations of the neck (branchial cleft cysts/fistulae), ears (preauricular pits, hearing loss), and kidneys

Branchio-Oto-Renal (BOR) syndrome hearing loss

MHL, but can be CHL or SNHL

BOR syndrome inheritance pattern

autosomal dominant

BOR syndrome characteristics

pre-auricular pits, abnormal pinna, stenosis, atresia, fused ossicles, inner ear malformations, kidneys absent or underdeveloped

Cleft palate hearing loss

CHL

cleft palate inheritance pattern

autosomal dominant

cleft palate characteristics

malformed palate and/or lip, risk of Eustachian tube dysfunction and otitis media

Goldenhar syndrome hearing loss

CHL, SNHL, MHL

Goldenhar syndrome inheritance

possibly hereditary, sporadic cases

Goldenhar syndrome characteristics

unilateral problem with eye and facial malformations, unilateral microtia, atresia, pits/tags, ME problems, can impact heart, kidneys and CNS

Jervell and Lange Nielsen syndrome hearing loss

profound bilateral SNHL

Jervell and Lange Nielsen syndrome inheritance

autosomal recessive

Jervell and Lange Nielsen syndrome characteristics

cardiac arrhythmia

Landau-Kleffner syndrome hearing loss

auditory agnosia: normal ABR, abnormal behavioral

Landau-Kleffner syndrome inheritance

autosomal dominant

Landau-Kleffner syndrome characteristics

sudden or gradual onset aphasia and seizures; linguistic regression

Neurofibromatosis II hearing loss

progressive SNHL

NF2 inheritance

autosomal dominant

NF2 characteristics

bilateral vestibular schwannoma, balance problems, tinnitus, facial weakness

Pierre- Robin Sequence hearing loss

CHL

Pierre-Robin sequence inheritance

genetic, typically not hereditary

Pierre-Robin sequence characteristics

Micrognathia, retroglossia (tongue positioned too far back in mouth), otitis media with effusion

Stickler syndrome hearing loss

sloping high frequency SNHL, possible cleft palate (MHL)

Stickler syndrome inheritance

autosomal dominant

Stickler syndrome characteristics

impacts connective tissue and collagen, inner ear structures, vision may be impacted, chronic otitis media

Treacher Collins syndrome hearing loss

CHL

Treacher Collins syndrome inheritance

autosomal dominant

Treacher Collins syndrome characteristics

craniofacial (malformed ears, microtia, anotia, atresia); hypoplastic/ankylosed or absent ossicles, vision may be impacted

Usher syndrome hearing loss

SNHL, degree depends on type

Usher syndrome inheritance

autosomal recessive

Usher syndrome characteristics

Retinitis pigmentosa

Onset in first 10 years (Type I) or later (Type II)

Vestibular problems in Type I

Waardenburg syndrome hearing loss

SNHL

Waardenburg syndrome inheritance

autosomal dominant

Waardenburg syndrome characteristics

pigmentation abnormalities (white forelock, heterochromia)

Wolfram syndrome hearing loss

bilateral progressive sloping high frequency SNHL

Wolfram syndrome inheritance

autosomal recessive

Wolfram syndrome characteristics

diabetes, intellectual impact

What are the 4 types of atresia?

Type A - meatal; narrow entrance into ear canal, unaffected TM, ossicles, inner ear

Type B - partial: very narrow bony and cartilaginous ear canal, TM may be malformed, ME and inner ear usually unaffected

Type C - total: no ear canal, absent TM, ossicular malformations

Type D - hypopneumatic: no ear canal, absent TM, ossicular malformations, mastoid pneumatization

What are exostoses?

broad, round, bony growths in osseous portion of EAC caused by exposure to cold temperatures (swimming, diving, surfing, etc)

can cause CHL

What is furunculosis?

raised, reddish lesions at base of hair follicles on outer EAC

What is Herpes zoster oticus?

lesions/blisters on pinna as result of chicken pox virus

possible facial swelling, weakness and paralysis (Ramsay Hunt Syndrome)

can cause SNHL, acoustic reflexes may be elevated/absent depending on facial nerve involvement

What are osteomas?

Pedunculated benign tumors in osseous EAC (appear as growth with NARROW base [compare to exostoses with round/wide base])

can cause CHL if large enough

What is pericondritis?

infection of pinna, typically resulting from trauma

What is a cholesteatoma?

Overproduction of keratin from squamous cell epithelium within middle ear, often in epitympanum, often unilateral

• Acquired due to chronic inflammation and infection of ME

• Congenital related to embryonic epithelial cell nests

Symptoms: chronic ME issues, aural fullness, HL, dizziness, numbness of muscle on affected side

Tymps: Ad or B

HL: unilateral CHL or MHL

What is disarticulation of ossicular chain?

continuity of ossicles is disrupted due to congenital abnormalities, ear infections, or trauma

often at incudostapedial joint

Tymp: Ad

HL: CHL (can be MHL)

What is a glomus tumour?

A paraganglionoma that arises from the paraganglion cells in the jugular bulb

Hallmarks: pulsatile tinnitus, red mass visible behind TM, Brown’s sign (blanching is seen with pneumatic pressure); continuous tympanometry matches heartbeat

Can cause CHL or MHL, unilateral

What is otosclerosis?

Metabolic alteration of temporal bone in otic capsule causing stapes footplate to mineralize around oval window and fixate

Often in female hormonal changes (after birth or perimenopause)

Hallmarks: autophony, difficulty hearing when chewing, Willis paracusis (better hearing in noise, LF CHL masks background noise), Schwartze’s sign (TM is reddish/pinkish)

Describe the progression of HL during otosclerosis

Early: LF CHL due to increased ossicular stiffness; decreased amplitude and flattened slope tymp (As); excellent WRS; absent reflexes

Late: flat CHL due to increased stiffness and mass of ossicular chain (30-50 dB CHL), air-bone gap at all frequencies with exception of 2kHz (Carhart’s notch)

Wtf is Carhart’s notch?

3 factors contributing to bone conduction

1. Bone osc vibrates skull, stimulates hair cell (distortional BC)

2. Tiny lag in ossicular chain movement when skull is vibrating (inertial BC)

3. Bone osc vibrates air column around EAC, cause TM to move (osseotympanic BC)

With otosclerosis:

• Fixation of stapes to oval window compensates both inertial and osseotympanic BC (seen at 2kHz)

Why at 2kHz? —> natural resonant frequency of ME ossicles

Carhart’s notch does NOT represent cochlear damage at 2kHz —> is mechanical artifact of BC testing

Temporal bone trauma types

Longitudinal - may cause ME space issues, CHL

Transverse - otic capsule may be sheared

What is hemotympanum?

blood in ME space; visible on otoscopy; may be coming out of EAC if TM lacerated

What is tympanosclerosis?

White calcified plaques on TM, associated with chronic otitis media and inflammatory process of middle ear

May have low SA on tymp

What is autoimmune inner ear disease?

autoimmune response directed at inner ear common in middle-aged women

HL: progressive or fluctuating SNHL

What is diabetes mellitus and how can it affect hearing?

Elevated blood glucose levels and altered lipids and proteins cause vascular changes that impact the stria vascularis and other cochlear anatomy and the auditory nervous system

bilateral HF SNHL, may have postural instability due to neuropathy

What is enlarged vestibular aqueduct syndrome (EVA)?

Abnormally large vestibular aqueduct within temporal bone; typically diagnosed around age 3-4

general imbalance, poor coordination (vestib impacts)

progressive or fluctuating SNHL (may need flexible programming)

risk for major HL with head trauma

What is Meniere’s disease?

Excess endolmyphatic fluid due to underabsorption and/or overproduction

4 classic symptoms: episodic vertigo, roaring tinnitus, fluctuating unilateral SNHL, aural fullness

Typical presentation: aura (feeling an episode may begin), sudden onset vertigo (with or without nausea, vomiting), tinnitus, aural fullness

What is a drop attack in Meniere’s disease?

“drop attacks” or otolithic crisis occur later in disease process, due to stimulation of otoliths with excess endolymph

How is Meniere’s disease diagnosed?

Electrocochleography: increased SP/cAP ratio (why? see Jason notes)

How is Meniere’s disease managed?

Low sodium diet

Anti-dizziness meds (depress CNS)

Meclizine

Antivert

Valium

Surgical

• Injection of gentamycin

• P-100

• Endolymphatic shunt (channels endolymph into mastoid)

• Vestibular nerve section

What is meningitis?

Inflammation of meninges of brain and spinal cord due to bacterial or viral infection; can enter inner ear

symptoms: fever, stiff neck, persistent headache, nausea/vomiting, ossification (implications for CI)

can cause bilateral SNHL

What does hearing loss caused by ototoxicity present as?

Bilateral HF SNHL, progressive in nature, some drugs have longer progression path than others

What are loop diuretics and why are they ototoxic?

Ex: ethacrynic acid, furosemide, bumetanide, torsemide

• Used in tx of: congestive heart failure, renal failure, any disorder associated with fluid retention

Cause elimination of fluid from the body by interacting with Na-K-2Cl transporter

• Disrupts the fluid in the inner ear (stria vascularis, chemical make-up of inner ear)

What are aminoglycosides and why are they ototoxic?

(hint: most end in -cin or -sin)

Bactericidal anti-biotics for gram-bacterial infections with broad antibacterial spectrum

• Ex: amikacin, kanamysin, netilmicin, streptomycin, neomycin (most ototoxic), gentamicin (most commonly used)

Drug interacts with iron to make ROS, easily interact with molecules in the cells to damage RNA, DNA, proteins, ultimately causing cell damage and death

• OHC and type I vestib cells most susceptible

• IHC have higher concentration of glutathione (antioxidant) [also OHC in basal turn]

Why are some anti-cancer drugs ototoxic?

Ex: cisplatin (most ototoxic), carboplatin, oxaliplatin

Cause deterioration of OHC and stria vascularis

What is a perilymphatic fistula?

Perilymph leak from oval or round window which alters the pressure differences between the cochlear scalae

Related to barotrauma, head trauma, straining activities

Tullio’s phenomenon: vertigo induced by loud sounds

Hennebert’s sign: induction of vertigo and nystagmus by applying pressure to the external ear canal; may report dizziness during tympanometry

SNHL, typically unilateral

What is superior canal dehiscence?

thinning or opening in the bony covering of the superior SCC creating a fistula

symptoms: Tullio phenomenon (vertigo induced by loud sounds), Hennebert’s sign (pressure induced vertigo: coughing, sneezing, straining), hyperacusis to bone-conducted sound (hear pulse, eye movement, autophony), chronic disequilibrium, oscillopsia, sensation of blocking or fullness in ear

Conductive loss audiogram with acoustic reflexes and normal tymp

Increased VEMP (vestibular-evoked myogenic potential)

Decreased VOR gain in plane of superior canal

What is multiple sclerosis?

Autoimmune disease causing demylination

Symptoms: extremity numbness, tremors, loss of vision/double vision, speech/swallowing difficulties, vertigo, ataxia

ABR: possibly abnormal morphology and latency elongation with high stimulation rates

HL: asymmetric high frequency SNHL

What is ANSD?

Auditory neuropathy spectrum disorder; impaired function of auditory nerve

Adult: HL, difficulty in noise

Child: abnormal birth history, delayed milestones

ABR: present CM with rest of ABR absent or highly abnormal

Audio: varies from normal to severe/profound

OAEs: present but may progress to absent

AR: absent

What is a vestibular schwannoma?

benign tumor of vestibular branch of CN VIII originating from Schwann cells (cells wrapped around neurons helping with signal conduction)

Symptoms: gradual, unilateral tinnitus, progressive unsteadiness/vertigo, nausea, possible facial weakness depending on IAC involvement, headaches, aural fullness

Audiological findings:

• AR: retrocochlear pattern

• positive reflex decay

• unilateral SNHL

• rollover

• prolonged wave V

What is benign paroxysmal positional vertigo?

sudden onset vertigo caused by head movements in plane of affected SCC

caused when otoconia are displaced from the utricular macula’s otolithic membrane and migrate into one of the 3 semicircular canals.

In stable conditions, this is not necessarily a problem, however when the endolymph lags during head movement, the displaced otoconia shifts within the fluid, and the subsequent stimulus is unbalanced with respect to the opposite ear, inappropriately causing symptoms of dizziness, spinning, and/or swaying

Typically no auditory symptoms, can be treated with canalith repositioning

What are canalithiasis and cupulolithiasis

Canalithiasis: free floating otoconia in SCC

Cupulolithiasis: otoconia adhered to cupula, causes more persistent nystagmus as added mass on cupula delays deflection back to resting position

What is benign paroxysmal vertigo of childhood?

common, self-limiting disorder in children aged 2–6, characterized by sudden, brief (seconds to minutes) episodes of spinning dizziness, vomiting, pale skin (pallor), and fear, with full recovery; potential precursor to migraines

What is cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS)?

rare, slow-progressing genetic neurodegenerative disorder

defined by a triad of symptoms—ataxia, sensory neuropathy, and bilateral vestibular loss

resulting in severe balance issues, dizziness, and oscillopsia (blurred vision) that progresses over decades

What is Mal de debarquement syndrome?

Rare neurological disorder characterized by a persistent sensation of rocking, swaying, or bobbing

typically occurring after passive motion exposure like cruises, flights, or long car rides. Symptoms can last months, uniquely alleviated by re-exposure to motion

Treatment is limited, optokinetic rehabilitation (using visual stimuli) has highest success rates

What is INO?

Internuclear ophthalmoplegia (INO)

Impaired eye adduction (inward movement) on the side of the lesion and abducting nystagmus in the other eye

What is achondroplasia?

Skeletal dysplasia, causing disproportionate short-stature dwarfism, characterized by a large head, short limbs, and normal trunk size; mutation on FGFR gene

Achondroplasia inheritance pattern

autosomal dominant

Achondroplasia identifiers

short-limbed dwarfism, enlarged head, depressed nasal bridge, short/stubby hands, lordotic lumbar spine (exaggerated curve in lower back), protruding abdomen

Achondroplasia auditory findings

Ear infections common

CHL or SNHL

What is Apert syndrome?

genetic disorder characterized by the premature fusion of skull bones (craniosynostosis), causing a peaked head, midface hypoplasia, and severe webbing of fingers/toes

Apert syndrome genetic inheritance

autosomal dominant

Apert syndrome identifiers

fused fingers and toes (syndactyly)

possible stenosis or atresia due to craniosynostosis

Apert syndrome audiologic findings

Bilateral flat CHL; can be SNHL

What is AUNA1?

Nonsyndromic genetic mutation causes ANSD with late teen onset; inherited autosomal dominant

What is CULLP?

Congenital unilateral lower lip palsy

unilateral facial paralysis when baby cries

autosomal dominant or due to compression of nerves during birth

possible SNHL

What % of genetic hearing loss is non-syndromic?

70%

What are some general characteristics of non-syndromic autosomal dominant HL?

Severity varies but is generally less severe and progressive starting in high frequencies and moving to low frequencies

What is the typical onset of non-syndromic autosomal dominant HL?

Post-lingual onset, presents typically in 1st or 2nd decade of life

Examples of non-syndromic autosomal dominant HL?

DFNA2, DFNA6/14/38, DFNA9

What is DFNA2?

One of the more common causes of non-syndromic autosomal dominant HL; post-lingual high frequency HL, with variable presentation and tinnitus. Mimics presbycusis by with an earlier onset and familial link

What gene does the DFNA6/14/38 impact?

WFS1

What type of HL does DFNA6/14/38 mutations cause?

low frequencies HL before the age of 10 and progressing to impact more of the frequency range

Why is HL caused by DFNA6/14/38 not identified in NBHS or school screenings?

HL at birth may not be in the moderate/severe range to be caught via screening protocol; school testing does not go below 500 Hz and only tests to 35dB and the HL may be milder than that (at that point)

What gene does DFNA9 encode for and what is it involved in?

the Coch gene is involved in auditory and vestibular function

What does a mutation in DFNA9 cause?

Auditory and vestibular dysfunction with symptoms suggestive of Meniere’s disease

How does HL caused by DFNA9 present?

HL progresses from severe to profound across the entire frequency range eventually

What is the phenotype of non-syndromic autosomal recessive HL?

congenital, pre-lingual, severe to profound (more severe then non-syndromic autosomal dominant HL), sensorineural

Examples of non-syndrome autosomal recessive HL?

DFNB8/10, DFNB12, DFNB1, ANSD (AUNA, OTOF)

What is DFNB8/10?

two mutations on the same chromosome that causes HL that is precipitously sloping in the high frequencies and progresses to involve more

What is the difference between DFNB8 and DFNB10?

DFNB8 presents with post-lingual onset during childhood, DFNB10 is pre-lingual