Syndromic Hearing Loss and Deafness Flashcards
Importance of epidemiology
to study the effect on society and determine what measures to take at a governmental or state level
ex. Covid;
Syndromic
multiple systems
nonsyndromic
one condition
How many babies are born with genetic/birth defects
1 in every 33
Epidemiology
looking at population outcomes
- study of how diseases spread and why they affect some groups more than others.
Incidence of HL
looking at new cases of defects
- how many over time
prevalence of HL
the existing # of cases
ways to reduce birth defects
- 400 micrograms of folic acid daily
- up to date on immunizations
- avoid tobacco, smoke, drugs, alcohol
- insect bites
what is the most common sensory deficit in humans
hearing loss
HL is ____ in women and _____ in men
lower, higher
Black’s have _____ HL than white people
less
monogenic
single gene mutation
ex. A replaced for G
Complex or Multifactorial Inheritance
causes of HL include genetic & environmental factors acting independently & together
- Ex. certain ototoxic medications can contribute to HL in individuals with a genetic predisposition.
What ways does the environment (non genetic) lead to pre-lingual deafness
- Infections
- Extreme prematurity
- Ototoxicity
Gene mapping
the approximate or exact location of a gene on a chromosome
-chromosome,arm,band,region
Gene cloning
production of exact copies of a gene or DNA sequence
Syndromic loci
disorders show abnormalities in many areas
Nonsyndromic loci
nonsyndromic disorders are not associated with another other symptoms or disorders
DFN
deafness neurosensory
DFNA
autosomal dominant deafness neurosensory
DFNB
autosomal recessive deafness neurosensory
DFNX
X linked recessive deafness neurosensory
DFNY
Y linked deafness neurosensory
DFMN
modifer deafness neurosensory
AUNA
auditory neuropathy deafness neurosensory
OTSC
otosclerosis
modifer gene
type of gene that alters the expression or effect of other genes.
-Instead of directly causing a particular trait or characteristic, modifier genes influence the outcome or severity of traits controlled by other genes.
pleiotropy
when one gene influences two or more seemingly unrelated phenotypic traits.
- when ONE gene exhibits multiple phenotypic expressions
- ex.Marfan’s Syndrome
Homeostasis
the ability of an organism or a cell to maintain internal equilibrium by adjusting its physiological processes
Inner ear homeostasis
ionic balance of perilymph and endolymph within the ear
what is needed for proper inner ear function?
a tight control on the ion movement across the cell membranes is necessary
- Hair cell functions
- Regulation of extracellular endolymph and perilymph
- Conduction of nerve impulses
The major ions involved in inner ear homeostasis are _____ &______. ______ & ______ also play a significant role.
- sodium (NA +), potassium (K+)
- chloride (Cl-), calcium (CA2+)
Disorders of cochlear HL & vestibular dysfunction are caused by_____.
disruption of ion homeostasis
what causes disorders of ion homeostasis
disruption of the strial ion transport mechanism is the final pathway
What is the majority of non-syndromic HL due to?
the alteration of proteins that prevent movement of potassium from the organ of corti to the lateral wall and into the stria
what are the two disorders of ion homeostasis
- endolymphatic hydrops
- endolypmphatic xerosis
endolymphatic hydrops
increased potassium transport in the endolymph or increased endolymph production
-Ex. meniere’s disease
endolypmphatic xerosis
decreased potassium transport in the endolymph or decreased endolymph production
- related to connexin (causing HL in humans)
endolypmphatic xerosis is belived to be the cause of ?
hearing loss in humans
- Connexin 26
- absence of KCNE1 & KCNQ1
how do we classify genetic deafness and hearing loss?
- chromosome disorders
- external ear changes (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)
cytogenetics
studies the cell, primarily the chromosome, structures and functions
-looking at the number and structure
chromosomal vs. single gene
whole body vs. system
Aneuploidy
abnormality in the number of chromosomes in a cell, where the whole chromosome is affected rather than just a segment of it.
what is a characteristic of chromosomal abnormalities?
- intellectual disabilities
- abnormal growth patterns & multiple systems involved
monosomy
the presence of only one copy of a particular chromosome in a cell, instead of the usual two copies.
trisomy
the presence of an extra copy of a chromosome in a cell, resulting in a total of three copies of that chromosome instead of the usual two
monosomy vs trisomy in terns of life expectancy
- monosomy lethal
- trisomy SOME are livable
what is the monosomy exception?
the loss of a sex chromosome can result in a live birth
what are the 3 autosomal trisomies and 1 sex trisomy that can survive to term?
13, 18, 21, & X
- x is a subcategory of 21
Trisomy 13
Patau Syndrome
- short life span
- intellectual disability, blindness (coloboma’s- missing pieces of tissue), cleft lip, heart defects and extra toes/fingers
audiological findings of trisomy 13
- abnormal helices
- low-set ear
- most children show a severe to profound bilateral SNHL or deafness
trisomy 18
Edwards syndrome
- extra chromosome 18
-short life span, majority will die within 1st year
-intellectual disability, seizures, small mouth with arched palate, small lower jaw, clenched hands and heart defects
trisomy 18 audiological findings
- malformed and low set pinna
- abnormal ME/IE
- severe HL or deafness
what is the most common chromosome defect in humans
trisomy 21 (down syndrome)
trisomy 21
down syndrome
- intellectual disability
- IQ decrease with age
- flattened facial features
- large tongue
- short limbs
- poor muscle tone
- heart disease
trisomy 21 audiological findings
low set pinna
narrow ear canal
- conductive, SNHL, or Mixed
Of the human trisomies which exhibits the most serve birth defects?
trisomy 13
what are the 3 ways down syndrome is inherited
- nondisjunction
- robertsonian translocation
- mosaicism (x-inactivation):
- only 1% very rare
nondisjunction inheritance
a pair of 21 chromosomes fails to separate in either the egg or sperm and as the embryo develops the extra chromosome is replicated in every cell of the body
robertsonian translocation
- the chromosome breaks at its centromere & the long arm fuses to form a single chromosome with a single centromere.
- the short arms will fuse together & are usually lost
mosaicism
an individual has two or more populations of cells with different genetic makeup within their body derived from a single zygote
what does mosaicism explain in rare autosomal dominant conditions in offspring when the parents are phenotypically normal
unusual clinical observations such as:
Somatic: achondroplasia (dwarfism), hemophilia, some bone diseases
Sex: klinefelter & turner syndrome
what is the germ cell mosaicism
X-inactivation
x-inactivation
- only happens in women
prevents females from having twice as many x chromosomes as males
-since females get two x’s, one at random will be turned off
how does x-inactivation cause down syndrome
some of the inactivated genes are actually expressing creating a mosaic
ring chromosome
occurs when an abnormal chromosome forms a ring structure
- one chromosome usually intact the other forms ring
how does a ring chromosome form
both ends of a chromosomes break and the broken ends fuse at the breakage points
- broken pieces are lost & any genes they contain
- like breaking a stick and gluing the ends together it will never be perfect again
what chromosomes do ring chromosomes occur in ?
any chromosome but more commonly acrocentric chromosomes
- r13, r14, r15, r21, r22
chimerism
the presence of two sets of DNA or organisms that do not match the DNA of the rest of the organisms
what happens with chimerism
two non-identical twin embryos merging together instead of growing on their own
- Hermaphroditic: male and female sex organs
turner syndrome
genetic condition where females are born with only one X chromosome
- because there is only one X chromosome present, any recessive traits carried on the X chromosome will be expressed phenotypically in females, even though they are recessive.
characteristics of turner syndrome
- short stature with thick or webbed neck
- immature gonads (infertility)
-IQ slightly below normal
what is the karyotype of turner syndrome
45,X0
audiological findings of turner syndrome
- low set pinna, narrow ear canal
- recurrent ear infections and OM
klinefelter’s syndrome
occurs when a male is born with an extra X chromosome, resulting in a karyotype of 47,XXY instead of the typical 47,XY.
klinefelter’s syndrome characteristics
-tall/thin with long legs
-hypogonadism around puberty with extra breast tissue
-male gonads but they are not functional
-IQ in low to normal range
-behavioral and psychosocial problems
klinefelter’s syndrome audiological findings
- SNHL
- discrimination & delayed speech development
are turner and klinefelter inherited conditions or spontaneous mutations?
spontaneous mutations
