Chromosomal Disorders (Congenital Monogenetic HL) Flashcards
what is cytogenetics
branch of genetics that studies structure and function of the cell, especially chromosomes
what is a characteristic of chromosomal abnormalities?
intellectual disabilities
abnormal growth patterns & multiple systems involved
what is aneuploidy
numerical aberration of whole chromosome
only ____ autosomal trisomies and ___ sex trisomy can survive
3, 1
what are the trisomies that are survivable
13, 18, 21, X
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 causes an increase in incidence of chromosomal trisomies
advanced maternal age
what is trisomy 13
Patau syndrome
what are the clinical findings of trisomy 13
patau syndrome
brain, heart, difficulty breathing, cleft lip/palate vision problems, extra digits, deformed tectorial membrane - why they dont worry about hearing
rare chromosomal disorder and generally exhibits the most severe birth defects
trisomy 13, Patau syndrome
what are the audiological findings in Patau syndrome
abnormal helices
low set ear
most show severe to profound bilateral SNHL or deafness
what is trisomy 18
edwards syndrome
all trisomies have
heart defects, low infertility, intellectual abilities
what are the clinical findings of edwards syndrome
profound intellectual disability with seizures
clenched hands with overlapping fingers
high arched palate & small mouth
heart defects
audiologic findings in Edwards syndrome
malformed & low set pinnae
most probably severe HL or deaf
___ fetus have higher rates of miscarriage
males
what is the most common chromosome defect in humans
trisomy 21
what is trisomy 21
down syndrome
only ____ of Down’s are born, _____ are fatal
30%, 70%
why are people with downs living longer now
advancements in medicine, better able to understand what is going on and how to treat them
The incidence of births of children with Down syndrome increases with
the age of the mother
what are clinical features in down syndrome
flat face (zygomatic bone) and long tongue and short limbs
hypotonia - poor muscle tonew
audiologic findings of trisomy 21
low set pinna
stenoic ear canals, middle and inner ear defects
HL can be conductive, mixed, or snhl
what is stenosis
small ear canal
HL in 60% of cases with downs is
secondary to serious otitis media and impacted cermen in stenoic ear canals
what is microglossia and where is it seen
tongue doesn’t fit into the mouth, abnormal smallness of the tongue
down’s
is edwards syndrome mostly male or female
female,
males usually higher rates of miscarriage
what percentage is robertsonian translocation in down’s?
around 4%
features of robertsonian translocation in seen in
acrocentric chromosomes (13, 14, 15, 21, 22)
An acrocentric centromere partitions the chromosome into
long arm containing vast majority of genes and short arm with smaller proportion of genetic content
what happens during robertsonian translocation
participating chromosomes break at their centromeres and long arms fuse to form single chromosome with single centromere
short arms join together to form another product which contains nonessential genes and is usually lost within a few cell divisions
long arms coming together of the acrocentric chromosomes
robertsonian translocation
If RT joins long arm of chromosome 21 with long arm of chromosome 14 (or 15),
heterozygous carrier is phenotypically normal or balanced
unbalanced trisomy 21
causes down syndrome
balanced trisomy 21
normal
RT carrying 14 & 21 + extra chromosome 14 =
normal phenotype and heterozygous
Mom Carrier of RT - risk of 2nd trisomy 21 pregnancy =
10-15%
Dad carrier of RT -
risk is <2%
An offspring of RT carrier can inherit
unbalanced or balanced forms of trisomy 21
RT carrying 14 & 21 + extra chromosome 21 =
Down Syndrome
what is mosaicism
two or more cell lines (cell populations) that differ genetically in an individual or tissue but that are derived from a single zygote
Mosaicism in single genes can be either
somatic or germ cells
what does mosaicism explain in rare AD conditions in offspring whose parents are phenotypically normal
achondroplasia, hemophilia, some bone diseases
sex chromosome mosaicism conditions
mosaic klinefelter syndrom
mosaic turner syndrome
if the parents are normal how can you have dominant condition?
spontaneous condition
what is achondroplasia
dwarfism
what is another name for x inactivation
lyonization
what is x inactivation
form of germ cell mosaicism
females inherit ____ as many X chromosomes as males
twice
what does x inactivation do for females
prevents females from having twice as many x chromosome gene products as males
all women are mosaics
we have 2 x chromosomes and men have xy
if both x remained active, we would have too many genes
one x is inactivated (random)
once inactivated will it remain inactivated thorughout the lifetime of the cell
yes
what happens if some of inactivated x genes are still expressing
only happens in women which is why autoimmune disorders mostly affect women
these genes create proteins that should not be there
is x inactivation variable
yes
What is a barr body
random inactivated x that shows up as a darkened condensed chromosomal region in the cell
females are a mix of
mix of Xm and Xp
what are 3 ways down’s can be inherited
trisomy 21 (nondisjunction)
translocation
mosaicism
what % is nondisjunction
around 95% of cases
what % is translocation
approx 4% of cases
what % is mosaicism
around 1% of cases
what is nondisjunction trisomy 21
prior or at conception, pair of 21 chromosomes in either sperm or egg fails to separate
as embryo develops extra chromosome is replicated in every cell of the body and accounts for an extra chromosome 21
what is translocation in trisomy 21
part of chromosome 21 breaks off during cell division and attaches to another chromosome (usually chrom 14)
total number of chromosomes in cells remain 46 but presence of an extra part of chromosome 21 causes the phenotype of down syndrome
what is mosaicism
occrus when nondisjunction of chromosome 21 takes place in one but not all the initial cell divisions after fertilization
when this happens mixture of two types of cells occur with usual 46 chromosomes and others containing 47 (containing the extra 21)
individuals with mosaic downs have
could have fewer characteristics of downs but it is difficult to broadly generalize due to variability of the condition
does mosaicism take place in multiple cells
no only one
what is a ring chromosome
rare genetic condition caused by having an abnormal chromosome that forms a ring
when ring forms both arms break and broken ‘sticky’ ends fuse at the breakage points
broken fragments are lost and any genes that were on them
can chromosomes happen on any chromosome
yes
what are the most common ring chromosomes
the acrocentric ones
r13, r14, r15, r21, r22
how are majority of ring chromosomes inherited
99% from sporadic mutatiosn
can ring chromosomes be inherited
yes
approx 90% are from mother ring chromosomes associated with reduced fertility in men
ring chromosomes have effects on
cell growth
what can happen to a ring chromosome during cell division
may become entangled
broken
double in size
what is mosaicism
resulting cells that arise with the wrong amount of chromosome material (too much or too little)
what is chimerism
can manifest as the presence of two sets of DNA or organs that do not match dna of the rest of the organism
what is often the result of chimerism
two non-identical twin embryos merging together instead of growing on their own
what are characteristics of chimerism
hermaphroditic, have both males and female sex organs
can chimerism have different patches of dna thorughout the body
yes
what is the karyotype of turner syndrome
45 X0
which x is absent in 80% of cases
paternal x
what are the clinical features of turner syndrome
short stature and thick/web neck
wide chest and streak gonads
iq slightly below normal
what is turner syndrome
condition where x linked recessive trait may express phenotypically in females because only one x chromosome is present
what is a streak gonad
immature gonads
infertile
what are the audiologic findings of turner syndrome
low set protruding pinna and narrow ear canals
recurrent ear infections and chronic otitis media
long term consequences of ear infections?
speech and language development delays
how do babies learn language
incidental learni g
x linked recessive - will a female show phenotype of turner syndrom?
no because the other x will balance itout
what is the phenotype of turner syndrome
they look like females
what is the single most common cause of male infertility?
klinefelter’s syndrome
what is klinefelter’s syndrome
47, xxy
they have two XX and a Y
extra sex chromosome
phenotype is a male because of the Y
47 xxy
klinefelter syndrome
what are the clinical features
tall and thin with disproportionately long legs
development normal until puberty
poor attention and judgment
behavior and psychosocial problem
what are the audiological features of Klinefelter’s syndrome
SNHL in cases reported with poor auditory discrimination and delayed speech development
