nonsyndromic HL and deafness Flashcards
modifier genes
modify the severity of HL, making it worse or mild
-with the example of connexin, depending on what gene is affected, this will alter the severity
what is the most sensible guess for inheritance of a non-syndromic HL
recessive as this is the majority of the inheritance
AD non-syndromic HL examples
otosclerosis and DFNA5
what do almost AD conditions show
post-lingual progressive HL but differ in :
-age of onset
-rate or progression
-ultimate degree of HL
-vestibular invovlement
otosclerosis
ossification of the stapes footplate into the oval window
-AD or can be spontaneous
-incomplete penetrance and varying expressivity
-will commonly present as a complex genetic disorder
-genes affected cause abnormal bone metabolism but there are multiple genes that can be affected
what is otosclerosis triggered by
combination of genetics, environmental, hormonal and other factors
-can often present within pregnant women due to hormones
pathogenesis of otosclerosis
a focal disease unique to the temporal bone
-disease of abnormal bone remodeling of the otic capsule
-no remodeling of the otic capsule occurs following embryologic development
site of lesion for otosclerosis
otic capsule
DFNA5
AD progressive SNHL
-HL is present in childhood and becomes worse with age
AR non-syndromic HL examples
connexin
what do AR conditions usually show
severe to profound SNHL that is pre-lingual in origin
-over 50% of AR HL is caused by connexin
what is connexin
a protein found in the cells throughout the body
-however it is not found in the cochlear hair cells but rather in the nonsensory epithelial cells and supporting cells
what is the gene for connexin
GJB
-GJB2, GJB6 and DFNB1/3
connexin’s structures
hexagonal array of proteins within the membrane of each cell that when lined up together can create a gap junction
-groups of 6 and wrapped around the connexon
what does the gap junction do in terms of connexin
permits ion transfer between cytoplasm of cells
-when opens the potassium goes through
-when closed potassium does not go through
importance of connexin protein
important to intercellular communication
what happens if connexin is mutated
the gap junctions will not open or close which results in no regulation
how does the mendelian law’s relate to connexin
second law (independent assortment)
-connexin is an example of how this law does not hold true due to the close relation of the genes for connexin 26 and 30 one can influence the expression of the other
what disease is related somehow to connexin 32
x linked charcot-marie-tooth disease
what is the most common allele mutation in connexin 26
35delG
-a frameshit mutation that will code for a different protein
audiologic findings with connexin 26
congenital HL
-severity of HL can be mild to profound
-usually bilateral
-wide variability
-sudden HL can occur
what else can occur with certain connexin phenotypes
skin diseases
-this is due to the protein being found throughout the body
-causes some patients to not be good CI candidates due to skin fragillity
what is usually the best intervention for patients with Cx26
CIs
-speech intervention needs to occur as well
x-linked non-syndromic HL examples
stapes fixation with perilymph gusher
stapes fixation with perilymph gusher
occurs when you are born with the stapes footplate within the oval window
-occurs during surgery to fix it and perilymph leaks out causing sudden HL
-without the surgery, HL can be mixed or progressive
mitochondrial non-syndromic HL examples
aminoglycoside induced ototoxicity
aminoglycoside induced ototoxicity
occurs when certain people take doses of this group of antibiotics and it causes irreversible HL
-occurs due to a mutation and the problem arises with not knowing you have the mutation
-experience sudden onset severe/profound SNHL when exposed to this medication
-not dose dependent
complex genetics
causes due to an interaction between genetics and the environment
-a lot of variants are needed for them to occur
-no clear inheritance pattern
-many are due to single nucleotide polymorphisms
what is an example of complex genetics
age related HL
-due to the root of the cause being hard to determine
age-related HL
not every older adult will have HL
-could be due to genetics, environmental factors, social life aspects
-multiple genes at play
-there is no diagnostic value
