DOWN SYNDROME

GROUP:38

NAME:PUGAZHENTHI RAVICHANDAR

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

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

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.

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 .

-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

-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

• -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.

-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.

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

• amniocensitosis-the sampling of

amniotic fluid using a hollow needle

inserted into the uterus, to screen for

developmental abnormalities in a

fetus.

-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

-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

-only 20%to 25% of trisomy conceptuses survive at birth.

-although this survived child develops congenital heart in 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

-

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

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

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

.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 -

-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

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

-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

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

-now this trisomy 21 disorder is also found in animals like tiger

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

partial trisomy 21:

-down syndrome can be diagonised in a patient of long arm of

chromosome 21 which are present in triplicate or 3 copies

-it is not identified by cytogenetically and can be rarely

identified

-by knowing what regions are triplicated in an chromosome 21

which are responsible for specific phenotype

-by knowing what regions have been triplicated before appearing

phenotype

-the chromosome 21 contains only few genes

-the most succesfull detection in down syndrome is the heart

defect region on chromosome 21 in 40% of down syndrome

patients

CURRENT INVESTIGATION-sorting out specific genes in chromosome 21 which are

responsible for down syndrome phenotype is a focus of current

investigation which uses mouse as a model.

-mice engineered contain extra chromosome 21 or even copy of

an entire human chromosome 21 which can show phenotypical

abnormalities such as in behaviour,brain function and cardiac

dvelopment

-nowadays mice is the potential promise for genetic diseases

research