Transcript An example: Down Syndrome, also known as Trisomy 21

Chromosomes are the structures that hold
our genes
 Genes are the individual instructions that
tell our bodies how to develop and function
They govern our physical and medical
characteristics, such as hair color, blood
type and susceptability to disease.
 Each chromosome has a p and q arm; p is
the shorter arm and q is the longer arm.
 The arms are separated by a pinched
region known as the centromere




The typical number of chromosomes in
a human cell is 46 - two pairs of 22
+ XX/XY
Holding an estimated 30,000 to
35,000 genes.
One set of 23 chromosomes is
inherited from the biological mother
(from the egg), and the other set is
inherited from the biological father
(from the sperm).




with a microscope , then Stainning
The chromosomes look like strings
with light and dark "bands"
A picture, or chromosome map, of all
46 chromosomes is called a karyotype
The karyotype can help identify
chromosome abnormalities that are
evident in either the structure or the
number of chromosomes.






The pairs have been numbered from 1 to 22, with
the 23rd pair labeled "X" and "Y."
In addition, each chromosome arm is defined
further by numbering the bands that appear after
staining
The higher the number, the further that area is
from the centromere.
The first 22 pairs of chromosomes are called
"autosomes"
Final pair is called the "sex chromosomes."
The sex chromosomes an individual has determines
that person's gender; females have two X
chromosomes (XX), and males have an X and a Y
chromosome (XY).
Karyotype )46, Xy)
Meiosis
Mitosis
Maternal Age
Environment



Chromosome abnormalities :
happen as a result of an error in cell division.
“Meiosis” is the name used to describe the cell
division that the egg and sperm go through
when they are developing.
Normally, meiosis causes a halving of
chromosome material, so that each parent gives
23 chromosomes to a pregnancy
Meiosis
Meiosis

Abnormality of chromosome
number or structure:
◦ Numerical Abnormalities
◦ Structural Abnormalities


When an individual is missing
either a chromosome from a pair
(monosomy) or has more than two
chromosomes of a pair (trisomy).
An example: Down Syndrome,
also known as Trisomy 21 (an
individual with Down Syndrome has
three copies of chromosome 21,
rather than two).
 Kleinfelter
Syndrome is an
example of trisomy the
individual is born with three
sex chromosome, XXY.
 Turner Syndrome is an
example of monosomy the
individual is born with only one
sex chromosome, an X.
Down
Syndrome
(Trisomy 21(
Down Syndrome (Trisomy 21(
Trisomy 2(
critical region:
A region on the long (q) arm of
chromosome 21
 Down syndrome causes mental
retardation
 a characteristic facial appearance
 multiple malformations

Associated with a major risk for
heart malformations
 a small but still significant risk of
acute leukemia
 3 copies of chromosome number 21






incidence of 1 in 660 and is by far the most
common chromosomal abnormality Slight
flattening of the face
A low bridge of the nose (lower than the
usually flat nasal bridge of the normal
newborn)
An epicanthal fold (a fold of skin over top of
the inner corner of the eye, which can also
be seen less frequently in normal babies)
A ring of tiny harmless white spots around
the iris
mental retardation
 The
risk of trisomy 21 is directly
related to maternal age
 Patients who will be 35 years or
older on their due date should be
offered chorionic villus sampling
or second-trimester
amniocentesis
Women younger than 35 years
should be offered maternal serum
screening at 16 to 18 weeks of
gestation
 The maternal serum markers used
to screen for trisomy 21 are alphafetoprotein, unconjugated estriol
and human chorionic gonadotropin

 The
use of ultrasound to
estimate gestational age
improves the sensitivity and
specificity of maternal serum
screening. (Am Fam Physician
2000;62:825-32,837-8.)
 Trisomy
21 is present in 95 percent of
persons with Down syndrome.
 Mosaicism, a mixture of normal
diploid and trisomy 21 cells, occurs in
2 percent.
 The
remaining 3 percent have a
Robertsonian translocation in
which all or part of an extra
chromosome 21 is fused with
another chromosome.
 The
reciprocal transfer of the
long arms of two of the
acrocentric chromosomes: 13,
14, 15, 21 or 22
 On rare occasions, other nonacrocentric chromosomes
undergo Robertsonian
translocation
a reciprocal transfer of the whole
long or short arms close to the
centromere
 A relatively common Robertsonian
translocation is between
chromosome 14 and chromosome 21
 In meiosis, a trivalent is formed.

Robertsonian translocation
TRANSLOCATIONS
Balanced reciprocal translocation
Balanced reciprocal translocation

Dysmorphic sign
Frequency (%)
Flat facial profile
Poor Moro reflex
Hypotonia
Hyperflexibility of large joints
Loose skin on back of neck
Slanted palpebral fissures
90
85
80
80
80
80
Dysmorphic sign
Frequency (%)
Dysmorphic pelvis on radiograph
Small round ears
Hypoplasia of small finger,
middle phalanx
Single palmar crease
70
60
60
45
Persons with Down syndrome
usually have mild to moderate
mental retardation
 School-aged children with Down
syndrome often have difficulty with
language, communication
 Adults with Down syndrome have a
high prevalence of early Alzheimer's
disease

Mental retardation
>95
Growth retardation
>95
Early Alzheimer's disease
75%
by age 60
Congenital heart defects
(atrioventricular canal defect,
ventricular septal defect, atrial septal
defect
40
Hearing loss
40 to 75
Ophthalmic disorders
(congenital cataracts,
glaucoma(
60
Epilepsy
5 to 10
Gastrointestinal malformations (duodenal
atresia,
Hirschsprung disease) 5
Hypothyroidism
5
Leukemia
5
Increased susceptibility to
infection (pneumonia, otitis media, sinusitis,
pharyngitis(
1-6
Infertility
>99% in men
anovulation in
30% of women
Estimated risk of Down syndrome
according to maternal age
 1/1,300
for a 25-year-old
woman;
 at age 35, the risk increases to
1/365
 At age 45, the risk of a having a
child with Down syndrome
increases to 1/30



If all pregnant women 35 years or older
chose to have amniocentesis
about 30 percent of trisomy 21
pregnancies would be detected
Women younger than 35 years give birth to
about 70 percent of infants with Down
syndrome
 Maternal
serum screening
(multiple-marker screening) can
allow the detection of trisomy 21
pregnancies in women in this
younger age group.
Alpha-fetoprotein (AFP)
 unconjugated estriol
 human chorionic gonadotropin (hCG)
 the serum markers most widely used to
screen for Down syndrome

AFP is produced in the yolk sac and fetal
liver.
 Unconjugated estriol and hCG are
produced by the placenta.
 The maternal serum levels of each of these
proteins and of steroid hormones vary with
the gestational age of the pregnancy.

With trisomy 21, second-trimester
maternal serum levels of AFP and
unconjugated estriol are about 25
percent lower than normal levels
 maternal serum hCG is approximately
two times higher than the normal hCG
level


The triple test can detect
approximately 60 percent of the
pregnancies affected by trisomy 21,
with a false-positive rate of about 5
percent.
 In
women older than 35 years,
the triple test fails to detect 10
to 15 percent of pregnancies
affected by trisomy 21.
If a patient has had a trisomy 21
pregnancy in the past, the risk of
recurrence in a subsequent pregnancy
increases to approximately 1-3
percent above the baseline risk
determined by maternal age
 Diagnosis
of a chromosome-21
translocation in the fetus or
newborn is an indication for
karyotype analysis of both
parents
 If both parents have normal
karyotypes, the recurrence risk is
2 to 3 percent
Chorionic villus sampling
10 to 12 weeks
0.5 to 1.5 %
Early amniocentesis
12 to 15 weeks 1.0 to 2.0 %
Second-trimester amniocentesis
15 to 20 weeks 0.5 to 1.0 %
Women who will be 35 years or older
on their due date should be offered
chorionic villus sampling or secondtrimester amniocentesis.
 Women younger than 35 years should
be offered maternal serum screening
at 15 to 18 weeks' gestation.


During the first trimester of the
majority of pregnancies, it is possible
to measure the size of the fluid area at
the back of the fetus’s neck, known as
the nuchal translucency or NT The
increasing size of the NT indicates a
greater risk of the fetus having
Down’s syndrome.
Ultrasound
Fluorescent In Situ Hybridisation
techniques
• chromosomes
13 (green), and
21 (red)

chromosomes 18
(aqua), X (green),
and Y (red).
2:1 ratio (Down's
Syndrome)
1:1 ratio (normal fetus)
Trisomy 18, 47 Ch.










incidence of about 1 in 3,000
There is a 3:1 preponderance of females to males
Thirty percent of affected newborns die within
the first month
50% by two months
and 90% by one year.
severe mental retardation
microcephaly
overlapping fingers, and rocker bottom feet
Neurologically they are hypertonic
Other common malformations include congenital
heart, kidney, .... abnormalities.
Trisomy 18, 47 Ch.












has an incidence of 1 in 5,000
Forty-four percent of affected newborns
succumb in the first month of life
and 69% by six months
Only 18% of the babies born with trisomy 13
survive the first year
microcephaly
microophthalmia (small eyes)
cleft lip or cleft palate
polydactyly (extra fingers)
congenital heart defects
urogenital defects
brain malformations
severe to profound mental retardation.
Turner Syndrome (45 , X)
45, X
Turner Syndrome (45,
X)
• Only females
• One X chromosome
• Or has two X chromosomes but one is
damaged
• Short stature
• Delayed growth of the skeleton
• Sometimes heart abnormalities
• Usually infertile due to ovarian failure
• Diagnosis is by blood test (karyotype)
• 1 out of every 2,500 female live births
worldwide
• Short neck with a webbed appearance
Kleinefelter
XXY
Kleinefelter47/XXY