this ppt was taken from genetics books 7th edition written by thompson and thompson

1. DOWN SYNDROME
GROUP:38
NAME:PUGAZHENTHI RAVICHANDAR

2. WHICH CHROMOSOME ARE RESPONSIBLE
FOR THIS DISORDER?
-MAINLY caused by trisomy of chromosome 21 in
which there is an meitic disjunction in
chromosome 21
-a patient with down syndrome has a 47
chromosomes instead of 46 in which there is an
extra s number of short segment of acrocentric
chromosome .
-acrocentric - a chromosome in which the
centromere is located near the end of an
chromosome.humans normally have 5 pairs of
acrocentric chromosomes

3. WHO HAS THE GREATER CHANCE FOR
ACQUIRING THIS DISORDER?
.INCREASED MATERNAL AGE
.MOST SEVERE IN MONOZYGOTIC TWINS WHO SHARE SAME ALLES IN
THEIR GENES
-LESS PREVEALENT IN DIZYGOTIC TWINS WHO HAS DIFFERENT ALEELS
IN THEIR GENES.
ALLES-any of the alternative forms of a gene that may occur
at a given locus

5. HISTORY OF THIS DISORDER
 -THIS SYNDROME WAS DISCOVERED CLINICALLY BY LANGDON
DOWN IN 1866 ITS CAUSE REMAINED MYSTERY FOR MANY YEARS
 ITS MAIN CAUSE WAS DETERMINED IN 1930 AND DOWN
SYNDROME BECOME THE FIRST CHROMOSOMAL ABNORMAL
DISORDER to be discovered.

6. phenotypical abnormalities or structural
variations caused by down syndrome
 down syndrome can be diagonised at birth or shortly after birth.
 the first sign of abnormality in infant is hypotonia in which there
is a state of low muscle tone which causes the reduction in
tension or resistance to stretch in a muscle .

7. -identified mainly by dysmorphic features that differ among each
individual in which there is an difference in the bodily
structure related mainly due to the congenital disorder,
genetic diseases or birth defect
-infants with very short height and brachycephaly-short skull
and flat occipat region
-infants have flat ears
-the mouth is open often showing protruding tongue
-brushfield spots on the iris of the eye

8. -abnormal palbepral fissures and epicanthal folds
-the hands are shor and broad and often with a single palmar
crease or simian crease -the fifth digit is incurved or
clinodactyl

9. • -down syndrome mainly causes mental retardation by
the end of first year
-the intelligence qutioent(iq) is usulally 30%to 60%
-many children with the down syndrome develop to
happy and self reliant person inspite of their limitations
-congenital heart diseases occurs one third in patients
with the down syndrome.
-
Duodenal atresia is the congenital absence or complete
closure of a portion of the lumen of the duodenum. It
causes increased levels of amniotic fluid during
pregnancy (polyhydramnios) and intestinal obstruction in
newborn babies.

10. -A tracheoesophageal fistula (TEF) is a congenital or acquired
communication between the trachea and esophagus. TEFs often
lead to severe and fatal pulmonary complications.
-these phenotypes result mainly due to the overespreesion of genes
in the chromosome 21 which can overexoressed in brain and heart
samples
-it does not occur in euploid individuals-having an exact multiple of
the haploid number of chromosomes.
diagnosis
-it can be diagnised by determining the genes in chromosome 21
which causes abnormal phenotype in an individual.

11. diagnosis
-it can be diagnised by determining the genes
in chromosome 21 which causes abnormal
phenotype in an individual.
-estimating maternal ages provide usefull
information
-diagonised mainly by chorionic villus sampling
and amnicensitosis
amniocensitosis-the

12. • amniocensitosis-the sampling of
amniotic fluid using a hollow needle
inserted into the uterus, to screen for
developmental abnormalities in a
fetus.

13. -in all maternal ages there is some loss of
amniotic fluid and at the the end of
pregnancy there is an great loss of amnitic
fluid- the loss of amniotic fluid can be
usually observed at 11th week to 16th week
which causes sponatneous abortion

14. -nearly all down syndrome patients develops alzeimer diseases
at earlier age than the typical age at onset
-the risk of having child at maternal age increaseses and the
meoitic erros during trisomy 21 increases after the maternal age
of 30
-the error occuring durin maternal meiosis is 90% which are
usually in meiosis 1 and the error ocurring during paternal
meisosis is 10% usually during meiosis 2 which are essential for
recurrence of risk

15. -only 20%to 25% of trisomy conceptuses survive at birth.
-although this survived child develops congenital heart e infants
disorder
-one fourth of the infants die due to heart defects before their 1st
birthday
-there is an chance of 15 fold increase in leukaemia
-premature infants also develop dementia(loss of memmory) which are
similar to alzeimer diseases (AD) and neurofibrillary tangles and
plaques
-

16. clinical manifestations:
-it is not difficult to identify this disorder and the karyotyping test gives us
conformation test to genetic counseling
-the specific abnormal karyotype responsible for down syndrome usually has an
little effetct of phenotype

17. why maternal aging causes down
syndrome?
-as we get older our egg cells become older
-this aged egg cells has less ability to
overcome meiotic non disjunction of
chromosomes
-the age for ocurrance of down syndrome is
30 to 45 years of age where the primary
oocytes are in prophase after first meiotic
division

18. what is robertsonian translocation ?
--it is a type of rearrangement involving two acrocentric
chromosomes which fuse near the centromere with the long
arm of an another chromosome with the loss of short arms -
the resulting chromosome has a balanced karyotype is 45
which are metacentric
-there are 5 pairs of acrocentric chromosomes in human
which has large number of genes encoding ribosomal RNA

19. .ROBERTSONIAN TRANSLOCATION- may be either psudocentric
or monocnetric
pseudocentric-without centromere
monocentric-having a single centromere
-the acrocentric chromosome combinations is found
in chromosome 14q21q and 13q14q -carriers
female have high risk of transmiting this
translocation segment to affected child in an
trisomy 21
-

20. -a carrier for robertsonian translocation invloves acrocentric
chromosome 14 and 21
there are three types of gametes result from robertsonian translocation
which are balance ,non-blanced and one is having normal chromosome
21 which accounts for 1in 3 in down syndrome

21. RISK OF DOWN SYNDROME:
-THE RECUURANCE OF RISK IN FAMILY IS ABOUT 1% OVERALL
-THE RISK IS ABOUT 1.4% MOTHER YOUNGER THAN 30 YEARS WHICH
ARE ALSO CAUSED BY MATERNAL ANXIETY DOES NOT INCREASE THE
RISK OF HAVING DOWN SYNDROME CHILD
-down syndrome can be detected prenatlly by cytogenetically or
comparitive hybridisation in involves analysis of chorionic villus or
amniotic fluid cells by comparative genome hybridisation(CGH)
.SAMPLINNG OF FETAL CELLS will cause loss of fetal tissue

22. -the population incidence of the down syndrome in live births is
currently
estimated to be about 1 in 800 of all births in older mother.
-at about the age of 30 the recurrance of risk is 1 in 25omy is
birth in mother
-the risk of translocation or partial trisomy is unrelated to
maternal age
-the paternal age have no appearance of risk.
-in us and canada 50% of pregnant women is 35 years of old
undergoes prenatal diagnosis but only 1% in fetuses where found
to have trisomy in 21
-circulation of fetal cells in maternal blood can also be
determined

23. 21q 21q translocation
- a 21q21q chromosome consists of two chromosome 21 long
arms
-An isochromosome is a chromosome that has lost one of its
arms and replaced it with an exact copy of the other arm
- monosomy 21 is rarely visible but it can be det ected by
postzygotically where there is an extra dose of chromosomal
material or lack of chromosome 21 at all

24. mosacicsm- when a person has
chromosomal abnormality is usualy present
in all cell
-2 or more chromosomal compelments is
found in an individual.this is called
mosaiscism which can be either nummerical
or structural.
-about 2% down syndrome patients are
mosaic
-the phenotype may be milder than
trisomy21 but there isvariation of
phenotypes differed from 21 chromosome
trisomy in embryo durin early development.
-the mildly affected patients are less
diagonised by karyotype

25. partial trisomy 21: