Syndromic HL & Deafness Flashcards
What do birth defects put children at risk for
lifelong physical learning and social challenges
what is epidemiology
study of population health
why is it important to study epidemiology
to understand the incidence of a certain disorder
what is incidence
new cases over a period of time
what is prevalence
existing cases
give an example of incidence
new cases of HL diagnosed at birth or after
give an example of prevalence
what is the existing number of people with HL
Why has there been an increase in genetic conditions?
because we are doing a better job of diagnosing those conditions, people are more aware of genetics and genetic testing etc.
How can the risk of birth defects be reduced?
taking 400 micrograms of folic acid every day (prevents conditions like spina bifida)
stay up to date with immunizations
get regular medical checkups & know family history
avoid tobacco and second hand spoke
avoid drugs and alcohol
prevent insect bites
why would preventing insect bites reduce risk of birth defect?
mosquitos can carry west nile zika and other viruses that are harmful during pregnancy
what is the most common sensory deficit in humans
hearing los
prevalence of HL ____ with every age decade
increases
the prevalence of HL is ____ in women than men, black vs white, in individuals across all age decades
lower
Profound hearing loss occurs in ______ per _____ births
1 per 1000 births
Lesser degree of loss occurs in _____ to _____ per ____ births
1 to 2 per 1000 births
how many people worldwide have HL that affects their ability to communicate?
70 million (26%?)
How many genes are associated with normal hearing
1% of the human genome
approx. 300 genes
How many syndromes include HL
over 400
of all monogenic conditions hearing loss is of
unparalleled genetic heterogeneity
what is genetic heterogeneity
many genes causing the same phenotype - hearing loss
what is a monogenic condition
single gene mutations
what are the causes of HL
genetic and environmental factors acting independently and together
the causes of HL (genetic & environment) are called what
multifactorial inheritance (or complex inheritance)
Complex or multifactoral inheritance is common in age-related hearing loss which affects about
50% of people > 75 years
what does idiopathic mean
we do not know the reason
prelingual
born with deafness
before learning language
postlingual
deaf after learning language
nonsyndromic
one condition
like just HL
syndromic
multiple systems
HL and something else
what are environmental/nongenetic prelingual deafness causes? and percentage?
25%
infections
extreme prematurity
ototoxicity
genetic causes of prelingual deafness and percentages
nonsyndromic (70%)
syndromic (30%)
examples of nonsyndromic causes of hl
AR (75-85%)
AD (15-24%)
Xlinked (1-2%
mitochondrial & others less than 1%
what is gene mapping
Identification of the approximate or exact location of a gene on a chromosome
the street address of the gene on a chromosome
chrom #, long/short arm, region, band
what is gene cloning
the production of exact copies (clones) of a particular gene or DNA sequence using genetic engineering techniques
How does gene cloning happen
dna is extracted from an organism and contains all of its thousands of different genes
the genetic engineer has to then find the specific gene to encode the specific protein of interest
syndromic disorders show abnormalities in many areas
syndromic loci
These are named according to their inheritance patterns
nonsyndromic loci
what does loci mean
location
DFN
deafness neurosensory
SNHL
A
autosomal dominant
B
autosomal recessive
X
x linked recessive
Y
Y linked
M
modifier
AUNA
auditory neuropathy
OTSC
otosclerosis
what is a modifier gene
genes that affect phenotypic and/or molecular expression of other genes
what is the common source of phenotypic variation in humans
modifier genes
Modifier genes can affect
the phenotypic outcome of a given genotype by interacting in the same or in a parallel biological pathway as the disease gene
what can modifier genes do
modulate expressivity (severity), penetrance, age of onset, progression of a disease, or pleiotropy (two or more seemingly unrelated phenotypic traits) in individuals with Mendelian traits
what is pleitropy
environment condition mimics a genetic condition
alopecia and thalidimide
what is inner ear homeostasis
balance bw different ions and fluids (peri and endo) in the inner ear
what happens if inner ear homeostasis is off
affects integrity of the inner ear and hae a problem with hearing
what is homeostasis
ability of an organism or cell to maintain internal equilibrium by adjusting its physiological processes
provide the definition for inner ear homeostasis
process by which chemical equilibrium of inner ear fluids and tissues is maintained
what is necessary for proper inner ear function
tight control on ion movement across cell membranes
what are the inner ear functions
hair cell functions
regulation of extracellular endolymph and perilymph
conduction of nerve impulses
what are the major ions involved in inner ear homeostasis
sodium (Na+)
potassium (K+)
what ions also play a role in inner ear
chloride (Cl-)
Calcium (Ca2+)
what controls ion homeostasis
numerous ion channels and transporters in the plasma membrane of cells, especially cells lining the scala media
does active H2O transport across cell membranes need to happen for inner ear?
yes
what causes 50% of all genetic HL
connexin
inner ear homeostasis in review
plasma membrane is the gatekeeper and there are genes that control those ions, without the working genes, the ions will not work and then there will be issues
what is the cause of majority of non syndromic genetic HL
alteration of proteins that prevent movement of K+ from the organ of corti to the lateral wall and into the stria
what is involved in potassium uptake in the ear?
stria
HL can result from
increase or decrease activity of the strial process
Increased K+ transport in the endolymph or increased endolymph production
endolymphatic hydrops
Decreased K+ transport in the endolymph or decreased endolymph production
endolymphatic xerosis
what is an example of endolymphatic hydrops
Meniere’s disease
excess of endolymph
what is an example of endolymphatic xerosis
connexin
what is believed to be the cause of HL in humans
endolymphatic xerosis
Responsible by itself for 50 to 80% of all AR hearing loss
connexin 26 related HL
what is connexin 26
Gene mutation results in abnormal connexin gap junction proteins
what are the genes required for hearing
regulatory
transmembrane transport
structural integrity
growth factor
cellular localization
what is regulatory genes in hearing
Transcription factors: POUfamily, EYA family, PAX-3
what are transmembrane transport in hearing genes
Gap Junction genes (K+ recycling – Connexin deafness), Potassium channel genes, Iodide transporter gene
what is structural integrity gene in hearing
Collagen genes, Unconventional myosin (steriocilia), Tectorin (tectorial membrane), Prestin (OHC)
growth factor gene in hearing
norrin (norrie disease)
cellular localization in gene hearing
Treacle (Treacher Collins Syndrome)
what is prestin
protein found in OHC that causes motility of them
what is the classification of genetic deafness & hL
chromosome disorders
external ear chances (treacher collins, BOR)
eye disease (ushers, norrie)
musculoskeletal disease (crouzon, stickler)
renal disease (alport)
cardiac system disease (jervell lange nielsen
neurologic (friedreich ataxia)
endocrine (pendred)
metabolic
integumentary (waardenburg)
no associated physical or mental characteristics
connexin HL
what is another common HL classification used
congenital genetic group
delayed onset
congenital non genetic
delayed onset non genetic
condition you’re born with but not genetic
virus infection causing birth defects
congenital non genetic group
what is cytogenetics
branch of genetics that studies structure and function of the cell, especially chromosomes
Why is hearing usually not adressed in chromosome defects?
so severely compromised, both physically and mentally, that hearing status is not adequately addressed
what are the 3 autosomal trisomies and one sex trisomy that can survive to term
13, 18, 21, X
what increases the incidence of chromosome trisomies
advanced maternal age
why do we think that with advanced maternal age you run the risk of trisomies? (oogenesis)
amount of time the egg spends in the diplotene stage
egg doesn’t complete meiosis stage until fertilization
by time is age is older, the egg has been in diplotene stage for this long
what is trisomy 13 syndrome
Patau
which trisomie exhibits the most severe birth defects
13
what are the clinical findings of Patau syndrom
trisomie 13
severe intellectual disability
brain, heart, difficulty breathing, heart issues eating, and vision problems
what are the audiologic findings of Patau syndrome
abnormal helices
low set ears
most severe to profound bilateral SNHL/deafness
cochlea and vestibular abnormalities
why is hearing not evaluated in Patau
low survival rate
significant and possible life threatening medical, neurological and cognitive impairments
