nonsyndromic HL and deafness

Question 1

modifier genes

Answer 1

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

Question 2

what is the most sensible guess for inheritance of a non-syndromic HL

Answer 2

recessive as this is the majority of the inheritance

Question 3

AD non-syndromic HL examples

Answer 3

otosclerosis and DFNA5

Question 4

what do almost AD conditions show

Answer 4

post-lingual progressive HL but differ in :
-age of onset
-rate or progression
-ultimate degree of HL
-vestibular invovlement

Question 5

otosclerosis

Answer 5

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

Question 6

what is otosclerosis triggered by

Answer 6

combination of genetics, environmental, hormonal and other factors
-can often present within pregnant women due to hormones

Question 7

pathogenesis of otosclerosis

Answer 7

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

Question 8

site of lesion for otosclerosis

Answer 8

otic capsule

Question 9

DFNA5

Answer 9

AD progressive SNHL
-HL is present in childhood and becomes worse with age

Question 10

AR non-syndromic HL examples

Answer 10

connexin

Question 11

what do AR conditions usually show

Answer 11

severe to profound SNHL that is pre-lingual in origin
-over 50% of AR HL is caused by connexin

Question 12

what is connexin

Answer 12

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

Question 13

what is the gene for connexin

Answer 13

GJB
-GJB2, GJB6 and DFNB1/3

Question 14

connexin’s structures

Answer 14

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

Question 15

what does the gap junction do in terms of connexin

Answer 15

permits ion transfer between cytoplasm of cells
-when opens the potassium goes through
-when closed potassium does not go through

Question 16

importance of connexin protein

Answer 16

important to intercellular communication

Question 17

what happens if connexin is mutated

Answer 17

the gap junctions will not open or close which results in no regulation

Question 18

how does the mendelian law’s relate to connexin

Answer 18

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

Question 19

what disease is related somehow to connexin 32

Answer 19

x linked charcot-marie-tooth disease

Question 20

what is the most common allele mutation in connexin 26

Answer 20

35delG
-a frameshit mutation that will code for a different protein

Question 21

audiologic findings with connexin 26

Answer 21

congenital HL
-severity of HL can be mild to profound
-usually bilateral
-wide variability
-sudden HL can occur

Question 22

what else can occur with certain connexin phenotypes

Answer 22

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

Question 23

what is usually the best intervention for patients with Cx26

Answer 23

CIs
-speech intervention needs to occur as well

Question 24

x-linked non-syndromic HL examples

Answer 24

stapes fixation with perilymph gusher

Question 25

stapes fixation with perilymph gusher

Answer 25

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

Question 26

mitochondrial non-syndromic HL examples

Answer 26

aminoglycoside induced ototoxicity

Question 27

aminoglycoside induced ototoxicity

Answer 27

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

Question 28

complex genetics

Answer 28

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

Question 29

what is an example of complex genetics

Answer 29

age related HL
-due to the root of the cause being hard to determine

Question 30

age-related HL

Answer 30

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