Down syndrome is a genetic condition in which an extra copy of chromosome 21 is present in an individual. It was initially observed and is described by a British Doctor John Langdon down in 1866 and third was called down syndrome after his name.
However the time he could not describe the reason of its occurrence and it was only later in 1959 when trisomy 21 was identified to be its cause.
Down syndrome is characterized by specific facial appearance, muscular hypotonia, cognitive delays and intellectual disabilities.Cognitive delays lead to normal behaviour and slower development of speech and language skills.
Down syndrome is identified through prenatal screening. parents with balanced translocation involving chromosome 21 are potential carrier of down syndrome and required genetic counseling to prevent the occurrence of this disorder.
Maternal age is highly correlated with the occurrence of down syndrome in child there is increases with the increase in age of mother.The chances are 1 in a age of 1000 at the age of 30, 1 in a 100 at the age of 40 ‚while it is 1 in a 30 at the age of 45.
Trisomy 21 is mainly caused by abnormality during cell division which can be of three types.Incomplete trisomy 21 a whole chromosome 21 is present as an additional copy that is instead of 23 chromosomes are present in an individual.
Of the total trisomies 21,90 — 93% cases are complete trisomy 21.This Extra copy comes from abnormal gamete in which chromosomes 21 has failed to separate during meiotic division.
Mosaic down syndrome or Mosaic Trisomy 21 is a rare condition found in <3% in which some cells of the body have an extra copy of chromosome 21,While others are normal and have only two of its copies. this mosaic of cells in the body of organisms.
This mosaicism appears as a result of abnormality is in cell division in the zygote leading to nondisjunction of sister chromatid to separate during Mitosis.
Translocation trisomy 21 is a type of trisomy which is found in only 2 — 4% cases. This condition arises due to translocation of some part of chromosome 21 usually the long arm, to another chromosome, most probably chromosome for 14.
The parent is a carrier in such cases and is normal in physical and mental aspects.In such individual no symptoms of down syndrome is appears as the consists of all the genes despite having 45 chromosomes (only one copy of chromosome 21).
However during formation of gametes in such a parent the extra part of chromosome 21 is received by a gamete after meiosis ‚which on fertilization give rise to the offspring with down syndrome.
The down syndrome (DS) phenotype:
Some 300 phenotype characteristics has been associated with down syndrome.A few dozen of these traits are present in most children suffering from this disorder and many of them appear at sibling at first glance.A child with the ages rapidly has an IQ range of 25 to 70 and has a flat facial profile and a broad saddle nose. The ear are small and round the tongue is large and Flat. The child has a protruding lower lip. A broad short skull thick shorthand with the shabby fingers and thick short feet and body. Down syndrome children usually have light coloured specks in the iris of their eyes are referred to as brushfield spots. About 30% have an simian crease and 30% have heart trouble.
Hernias and a marked susceptibility to infections are associated with the syndrome. They are usually retarded in physical development and are short statured.
Origin of down syndrome:
One of many ways in which the trisomy condition originate is through nondisjunction of chromosome 21 during meiosis.
Failure of paired homologus to disjoint during anaphase first or second can result in male or female gametes with the n + 1 chromosomes composition.
Following fertilization with a normal gamete the trisomy condition results. chromosome banding studies have shown that while the distal chromosomes may be derived from either mother or father defective ovum is most often the source.
Maternal /paternal age and down syndrome :
Clearly down syndrome more than any other syndrome shows marked relationship to maternal age.
A female is born with all the oocyte site will ever produce nearly 7 million. These remain in an arrested prophase l of meiosis from birth until ovulation, generally at this rate of one per menstrual cycle (about 28 days) after puberty.
A given Oocyte may remain in a state of suspended development for some 12 to 45 years or so. It has been observed that the accuracy of meiotic division decreases with the age of 30 the frequency of nondisjunction associated with chromosome 21 increase assistant substantially
For women over the age of 45 years of probability of producing a down syndrome child is about one in 40.
Higher than normal frequencies of children suffering from down syndrome have also been discovered for mothers under the age of 17.The exact reason however is not clear as yet. a convincing theory that make explain the relatively high incidence of down syndrome for both older and younger mother relates the frequency of nondisjunction to oestrogen levels.
Estrogen help to control the rate of meiosis in primary oocytes. Estrogen level decreases with the age of showing of meiotic process may make nondisjunction more likely.
Oestrogen levels do not stabilize following puberty until about the age of 20 the down syndrome children produced by very young mothers thus May reflect fluctuation in hormone levels.
If age of age-related factor increases the likelihood of nondisjunction then trisomies is involved in chromosomes other than chromosome 21 should also be more common in older and mother and even in younger than mothers. Infact , the incidence of trisomy 13 and 18 is higher in older women. other trisomies also be common in these women but because they are Lethal they are difficult to detect.