Translocation Health Dictionary

A chromosomal abnormality resulting in a variable degree of learning difficulties and a characteristic physical appearance.

People with Down’s syndrome have an extra chromosome (47 instead of 46). Affected individuals have 3 copies of chromosome number 21 instead of 2; the disorder is also called trisomy 21. In most cases, it is the result of a sperm or egg being formed with an extra chromosome 21. If one of these takes part in fertilization, the baby will also have the extra chromosome. This type of abnormality is more likely if the mother is aged over 35. A less common cause is a chromosomal abnormality known as a translocation, in which part of 1 parent’s own chromosome number 21 has joined with another chromosome. The parent is unaffected but has a high risk of having Down’s children.

Typical physical features of a person with Down’s syndrome include small face and features; sloping eyes with folds of skin that cover their inner corners; large tongue; and short, broad hands. People with Down’s syndrome have a greater than normal risk for certain disorders, such as a heart defect at birth (see heart disease, congenital), intestinal atresia (a narrowing in the intestines), congenital deafness, and acute leukaemia. Down’s syndrome children are especially susceptible to ear infections. A type of Alzheimer’s disease often develops after age 40.

Down’s syndrome is usually recognized soon after birth.

The diagnosis is confirmed by chromosome analysis.

Screening tests during early pregnancy, including ultrasound scanning, indicate those fetuses likely to have the syndrome.

Amniocentesis is then offered.... down’s syndrome

In humans there are 23 pairs of CHROMOSOMES. Male and female di?er in respect of one pair. In the nucleus of female cells, the two members of the pair are identical and are called X chromosomes. In the male nucleus there is one X chromosome paired with a dissimilar, di?erently sized chromosome called the Y chromosome. In the sex cells, after MEIOSIS, all cells in the female contain a single X chromosome. In the male, half will contain an X chromosome and half a Y chromosome. If a sperm with an X chromosome fertilises an ovum (which, as stated, must have an X chromosome) the o?spring will be female; if a sperm with a Y chromosome fertilises the ovum the o?spring will be male. It is the sex chromosomes which determine the sex of an individual.

Sometimes during cell division chromosomes may be lost or duplicated, or abnormalities in the structure of individual chromosomes may occur. The surprising fact is the infrequency of such errors. About one in 200 live-born babies has an abnormality of development caused by a chromosome, and two-thirds of these involve the sex chromosomes. There is little doubt that the frequency of these abnormalities in the early embryo is much higher, but because of the serious nature of the defect, early spontaneous ABORTION occurs.

Chromosome studies on such early abortions show that half have chromosome abnormalities, with errors of autosomes being three times as common as sex chromosome anomalies. Two of the most common abnormalities in such fetuses are triploidy with 69 chromosomes and trisomy of chromosome 16. These two anomalies almost always cause spontaneous abortion. Abnormalities of chromosome structure may arise because of:

Deletion Where a segment of a chromosome is lost.

Inversion Where a segment of a chromosome becomes detached and re-attached the other way around. GENES will then appear in the wrong order and thus will not correspond with their opposite numbers on homologous chromosomes.

Duplication Where a segment of a chromosome is included twice over. One chromosome will have too little nuclear material and one too much. The individual inheriting too little may be non-viable and the one with too much may be abnormal.

Translocation Where chromosomes of different pairs exchange segments.

Errors in division of centromere Sometimes the centromere divides transversely instead of longitudinally. If the centromere is not central, one of the daughter chromosomes will arise from the two short arms of the parent chromosome and the other from the two long arms. These abnormal daughter chromosomes are called isochromosomes.

These changes have important bearings on heredity, as the e?ect of a gene depends not only upon its nature but also upon its position on the chromosome with reference to other genes. Genes do not act in isolation but against the background of other genes. Each gene normally has its own position on the chromosome, and this corresponds precisely with the positon of its allele on the homologous chromosome of the pair. Each member of a pair of chromosomes will normally carry precisely the same number of genes in exactly the same order. Characteristic clinical syndromes, due to abnormalities of chromosome structure, are less constant than those due to loss or gain of a complete chromosome. This is because the degree of deletion, inversion and duplication is inconstant. However, translocation between chromosomes 15 and 21 of the parent is associated with a familial form of mongolism (see DOWN’S (DOWN) SYNDROME) in the o?spring, and deletion of part of an X chromosome may result in TURNER’S SYNDROME.

Non-disjunction Whilst alterations in the structure of chromosomes arise as a result of deletion or translocation, alterations in the number of chromosomes usually arise as a result of non-disjunction occurring during maturation of the parental gametes (germ cells). The two chromosomes of each pair (homologous chromosomes) may fail to come together at the beginning of meiosis and continue to lie free. If one chromosome then passes to each pole of the spindle, normal gametes may result; but if both chromosomes pass to one pole and neither to the other, two kinds of abnormal gametes will be produced. One kind of gamete will contain both chromosomes of the pair, and the other gamete will contain neither. Whilst this results in serious disease when the autosomes are involved, the loss or gain of sex chromosomes seems to be well tolerated. The loss of an autosome is incompatible with life and the malformation produced by a gain of an autosome is proportional to the size of the extra chromosome carried.

Only a few instances of a gain of an autosome are known. An additional chromosome 21 (one of the smallest autosomes) results in mongolism, and trisomy of chromosome 13 and 18 is associated with severe mental, skeletal and congenital cardiac defects. Diseases resulting from a gain of a sex chromosome are not as severe. A normal ovum contains 22 autosomes and an X sex chromosome. A normal sperm contains 22 autosomes and either an X or a Y sex chromosome. Thus, as a result of nondisjunction of the X chromosome at the ?rst meiotic division during the formation of female gametes, the ovum may contain two X chromosomes or none at all, whilst in the male the sperm may contain both X and Y chromosomes (XY) or none at all. (See also CHROMOSOMES; GENES.)... sex chromosomes

a variety of *leukaemia in which the type of blood cell that proliferates abnormally originates in the blood-forming (myeloid) tissue of the bone marrow. Myeloid leukaemias may be acute or chronic and may involve any one of the cells produced by the marrow. Blood cells in patients with chronic myeloid leukaemia contain a reciprocal *translocation between chromosomes 9 and 22 (see Philadelphia chromosome); molecular characterization of the translocation has led to the development of specific drugs to block the effects of this abnormality (see tyrosine kinase inhibitor).... myeloid leukaemia

an abnormal form of chromosome 22 that has a foreshortened long arm due to a reciprocal *translocation with chromosome 9. It is most commonly seen in the marrow cells of patients with chronic *myeloid leukaemia.... philadelphia chromosome

Variations from normal in the number or structure of chromosomes contained in a person’s cells. The cause is generally a fault in the process of chromosome division, either during the formation of an egg or sperm, or during the first few divisions of a fertilized egg. Chromosomal abnormalities are classified according to whether they involve the 44 autosomes or the 2 X and Y sex chromosomes. A complete extra set of chromosomes per cell is called polyploidy and is lethal.

Autosomal abnormalities cause physical and mental defects of varying severity. Some types of autosomal abnormality, known as trisomy, consist of an extra chromosome on 1 of the 22 pairs of autosomes. The most common trisomy is Down’s syndrome. Sometimes, part of a chromosome is missing, as in cri du chat syndrome. In translocation, a part of a chromosome is joined to another, causing no ill effects in the person but a risk of abnormality in his or her children.

Sex chromosome abnormalities include Turner’s syndrome, in which a girl is born with a single X chromosome in her

cells instead of 2, causing physical abnormalities, defective sexual development, and infertility. A boy with 1 or more extra X chromosomes has Klinefelter’s syndrome, which causes defective sexual development and infertility. The presence of an extra X chromosome in women or an extra Y chromosome in men normally has no physical effect but increases the risk of mild mental handicap.

Chromosomal abnormalities are diagnosed by chromosome analysis in early pregnancy, using amniocentesis or chorionic villus sampling.... chromosomal abnormalities