DOWN SYNDROME

GROUP:38NAME: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

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

• 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 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-

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 anlittle 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 centromeremonocentric-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 21there 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 iscurrently 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

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: