Hearing Loss Flashcards
List the types of hearing loss.
sensorineural
conductive
mixed
pre-lingual (congenital) vs post-lingual
What is sensorineural hearing loss?
when hearing loss is due to problems in the cochlea and back to the brain
What is conductive hearing loss?
problems moving the sound to the nerve
What is the difference between pre-lingual (congenital) vs post-lingual hearing loss?
pre-lingual (congenital) develops early prior to the development of speech
post-lingual develops after speech develops
List examples of anatomical anomalies of the inner ear.
Mondini dysplasia (abnormal structure of the cochlea) CHARGE (associated with absent semicircular canals)
What are the tests for hearing?
audiograms (measures softest sounds heard at different pitches; decibles vs hertz) Otoacoustic emissions (microphone plays sounds into the ear and earphone catches the sound that is reflected back) Auditory Brainstem Response (plays sound into ear and measures conduction to the nerve with electrodes ob the back of the head)
What are the most common subtypes of hearing loss?
DFNB (AR- prelingual)
DFNA (AD- postlingual)
DFNX (X-linked)
What are some non-genetic causes of hearing loss?
infections (CMV) low birth weight/prematurity jaundice medications (aminoglycosides and chemo) ototoxicity (loud noises and environmental exposures)
What is DFNB1?
AR
mutations to GJB2 gene which codes for connexin 26 (2 exon gap junction protein) which makes a junction with connexin 30 in cochlea to maintain potassium homeostasis for generating action potentials in response to sound
most common cause of pre-lingual, non-syndromic hearing loss (can be mild, moderate, severe, or profound) that is symmetrical
What other phenotypes are associated with mutations in the GJB2 gene?
AD variable onset and variable progression hearing loss
keratoderma with deafness
Vohwinkle Syndrome (AD- mutilating keratoderma with mild to moderate deafness)
KID/HID syndrome (keratitis, hyperkeratosis, ichthyosis, and deafness)
What GJB mutations cause deafness?
GJB1 (connexin 32 associated with XL CMT1)
GJB2 (connexin 26 associated with AR hearing loss)
GJB3 (connexin 31 associated with deafness/dermatoses depending on the mutation)
GJB6 (connexin 30 associated with AD or AR hearing loss when combined with connexin 26 mutations)
GJA1 (connexin 43 associated with AR hearing loss)
What other genes cause DFNB phenotypes?
SL26A4 (Pendred syndrome OR non-syndromic hearing loss with EVA)
MYO15A (severe to profound hearing loss in consanguineous families from Pakistan)
GJB6 (truncating mutations also abolish GJB2 expression; compound hets with GJB2)
What is DFNA?
AD hearing loss typically milder and post-lingual WFS1 (causes DFNA6) KCNq4 (causes DFNA2) COCH TECTA GJB3
What is Usher syndrome?
AR
USH1* genes
accounts for more than half of deafness+blindness and 18% of retinitis pigmentosa
List the subtypes of Usher syndrome and their symptoms.
Type I: profound hearing loss, absent vestibular function, retinitis pigmentosa in first decade
Type II: severe hearing loss, normal vistibular function, retinitis pigmentosa in second decade
Type III: progressive hearing loss, variable vestibular function, variable onset of retinitis pigmentosa
What genes are associated with each subtype of Usher Syndrome?
USH1B (MYO7A) USH1C (USH1C) USH1G (USH1G) USH1D (CDH23) USH1F (PCDH15) USH1E (21q) USH3A (CLRN1)
What is Pendred Syndrome?
AR
SLC26A4 (7q31)
What symptoms are associated with Pendred Syndrome?
congenital, severe to profound sensorineural hearing loss
Goiter (euthyroid) in late childhood or adolescence (10% will develop abnormal thyroid function)
vestibular dysfunction
abnormalities of temporal bone imaging
What is Long QT syndrome?
AR
variable penetrance
KVLQT1 (11p) or KCNE1 (21q) encode for potassium channel proteins
What symptoms are associated with Long QT syndrome?
congenital sensorineural hearing impairment with electrocardiographic abnormalities
fainting spells
sudden death
What is Wardenberg syndrome?
AD with some AR
Types I and III (PAX3)
Type II (MITF)
Type IV (SOX10, EDN3, EDNRB)
What symptoms are associated with Wardenberg syndrome?
Type I: heterochromia irides, dystopic canthorum, white forelock
Type Il: heterochromia, white forelock, early graying, no dystopia canthorum or facial dysmorphisms
Type III: Type 1 with limb abnormalities including contractures and muscle hypoplasia
Type IV: Type II with Hirschsprung disease
all have congenital sensorineural hearing loss
What is Branchio-Oto-Renal syndrome?
AD
EYA1 (40%)
SIX5 (5-6%)
SIX1
What are the clinical features of Branchio-Oto-Renal syndrome?
sensorineural, conductive, or mixed hearing loss branchial pits, cysts, and/or fistulas renal dysplasia or aplasia malformed pinnae (not symmetrical) ear pits/tags
What is Alport syndrome?
X-linked
COL4A3
COL4A4
COL4A
What clinical features are associated with Alport syndrome?
hematuria
nephritis with progressive renal failure
eye abnormalities (anterior lenticonus, cataracts, maculopathy)
progressive sensorineural hearing loss (onset in late childhood to early adulthood)
What other syndromes and conditions are associated with hearing loss?
Neurofibromatosis Turner Syndrome Osteogenesis Imperfecta CHARGE Treacher Collins Norrie Wolfram Deafness/Dystonia/Optic atrophy
What is STRC-related deafness?
sequence variants in STRC result in non-syndromic sensorineural hearing loss (DFNB16)
contiguous CATSPER2 and STRC genes deleted
homozygous microdeletions of 15q15.3
What symptoms are associated with STRC-related deafness?
male infertility and deafness
female deafness only
hearing loss is moderate to severe, early onset, and non-progressive
What is Auditory Neuropathy?
AR/AD/L/mitochondrial
mutations to OTOF (AR), DIAPH3 (AD)
preserved cochlear outer hair cell function but abnormal or absent auditory brain stem response
associated with CMT and Freidrich Ataxia
How is hearing loss/deafness managed?
hearing aids
amplification
speech and language therapy
cochlear implants (invasive with high complication rate)
