The human body is made up of billions of individual cells. Apart from the red blood cells, each cell contains a structure called a nucleus. Inside each nucleus are found long, thread-like bodies, the chromosomes. Chromosomes are made up of a short arm (designated by the letter 'p') and a long arm ('q'), joined at a point, the centromere. The ends of the two arms are called the telomeres. Chromosomes are made up of deoxyribonucleic acid (DNA) and proteins. The DNA of each cell, when stretched out, is around 2 m long. In chromosomes the DNA is coiled and much condensed. Chromosomes contain genes, which are special stretches of DNA. The genes provide the instructions that tell our bodies how to develop and function properly.

Apart from the mother's egg cells (ova) and the father's sperm cells (spermatozoa), every cell in the human body normally contains twenty-three pairs of chromosomes, giving forty-six chromosomes in total. There are thought to be around thirty thousand genes in each cell. Of the twenty-three pairs of chromosomes in each of these cells, one member from each pair is normally inherited from the father and the other member of each pair is normally inherited from the mother. The first twenty-two pairs of chromosomes are called the autosomes and are numbered from one to twenty-two, generally in order of length, chromosome 1 being the longest. The chromosomes in the twenty-third pair are called the sex chromosomes. They are labelled X or Y. Males normally have one copy of the X chromosome and one copy of the Y chromosome while females normally have two copies of the X chromosome in their body cells.

A mother's egg cells each normally contain only twenty-three chromosomes, made up of one copy each of chromosomes 1 to 22 and one copy of the X chromosome. A father's sperm cells also normally contain only twenty-three chromosomes, again made up of one copy each of chromosomes 1 to 22 but also either one copy of the X chromosome or one copy of the Y chromosome. It is the father's sperm that determines whether a child will be a boy (XY) or a girl (XX).

A person's chromosomal make-up is called their karyotype which can be described by a code of letters and numbers.

Chromosome abnormalities have, by tradition, been defined as those abnormalities large enough to be seen down a light microscope. With more recent and sophisticated analytical techniques, much smaller abnormalities that cause symptoms can now be detected. Chromosome abnormalities often involve many different genes and they can be classified into two main types, numerical abnormalities and structural abnormalities. If these arise during formation of an egg or sperm cell, then the abnormality would be passed on to every cell in the child's body. If the abnormality arises in one of the new cells produced soon after an egg has been fertilised by a sperm, then only a proportion of the child's cells will be affected and this is called mosaicism. When a person carries such an abnormality, they are at risk of displaying the symptoms of the associated chromosome disorder.

Numerical abnormalities
When cells carry complete extra sets of chromosomes, this is called polyploidy. When there is one extra complete set, to give sixty-nine chromosomes in total, then this is known as triploidy. Two extra sets of chromosomes, to give niney-two chromosomes in total, would be called tetraploidy.

When individual whole chromosomes are missing or extra, this is called aneuploidy. This can happen with any of the autosomal chromosomes (1 to 22) or the sex chromosome (X or Y).

If one extra complete chromosome is present, this is known as trisomy and the number of chromosomes in each affected cell would be 47. The most common disorder arising from a trisomy is Down syndrome (Trisomy 21). Two extra complete chromosomes would be called tetrasomy and the number of chromosomes would be 48. Three extra complete chromosomes would be called pentasomy and the number of chromosomes in each cell would be 49. If a complete chromosome is missing, this is known as monosomy and the number of chromosomes in each cell would be 45.

Examples of aneuploidy involving the sex chromosomes include XYY (male with one extra Y chromosome), XXY (male with one extra X chromosome), XXXY (male with two extra X chromosomes), XXXXY (male with three extra X chromosomes), XXYY (male with one extra X and one extra Y chromosome), XXX (female with one extra X chromosome), XXXX (female with two extra X chromosomes) and XXXXX (female with three extra X chromosomes).

Structural abnormalities
Structural chromosome abnormalities arise when there are breakages in chromosomes, leading to a net loss, gain or abnormal rearrangement of one or more chromosomes. Structural abnormalities include deletions and duplications, including those too small to be seen down the light microscope (microdeletions and microduplications) those near the end of the chromosome (subtelomeric deletions and duplications), ring chromosomes, reciprocal translocations (balanced or unbalanced), Robertsonian translocations (balanced or unbalanced), insertional translocations (balanced or unbalanced) and inversions (pericentric or paracentric). As analytical techniques improve, smaller and more subtle structural abnormalities can often be detected where previously a person's karyotype was thought to be normal.

Balanced and unbalanced reciprocal translocations
Balanced reciprocal translocations arise when breakages occur in two or more different (non-homologous) chromosomes with the resulting detached segments swapping places with each other. No chromosomal material has been lost or gained, just rearranged. Usually, carriers of a balanced reciprocal rearrangement will have no symptoms themselves. However, they run the risk of having problems at reproduction, e.g reduced fertility, miscarriage and/or the birth of a child with an unbalanced reciprocal translocation (in which there is both a net loss and gain of chromosomal material) and therefore symptoms. A small proportion of babies born with an apparently balanced reciprocal translocation will have symptoms. One of the reasons may be that the break has caused damage to a gene. Another may be that there is a microdeletion or microduplication that has caused the symptoms.

Robertsonian translocations
Balanced Robertsonian translocations arise when the short arms of two of the acrocentric chromosomes (chromosomes 13, 14, 15, 21 or 22) are lost and the remaining parts of the centromeres and the long arms fuse together. Although carriers of such balanced Robertsonian translocations would not be expected to have symptoms themselves, they run the risk of reduced fertility, miscarriage and/or producing babies with unbalanced chromosomes and therefore symptoms.

Balanced and unbalanced insertional rearrangements
Balanced insertions occur when a segment of one chromosome is inserted into a break in the arm of another chromosome. No chromosomal material has been lost or gained, just rearranged. Carriers of such balanced insertions should not have symptoms but they are at risk of fertility problems, miscarriage and/or the birth of a child with an extra or missing copy of the inserted chromosomal segment and therefore symptoms.

Deletions
A deletion (sometimes called a partial monosomy) involves loss of a segment of a chromosome. Deletions can occur near to the centromere (proximal deletion), nearer to the end of the chromosome (distal deletion), in the middle of a chromosome arm (interstitial deletion), at the end of the chromosome (terminal deletion) or as a tiny segment missing very near to the telomere (subtelomeric deletion). Deletions can cause symptoms due to loss of any genes contained within the deleted chromosomal segment.

Ring chromosomes
Ring chromosomes arise when the ends of both arms of a chromosome are lost and the remaining broken ends join together to form a ring shape. Thus a ring chromosome is essentially a double deletion. However, if a ring chromosome exists as an extra, supernumerary chromosome, then it is the material contained within the ring that is in effect duplicated.

Duplications/triplications
A duplication (sometimes called a partial trisomy) occurs when an extra copy of a segment of a chromosome is present. If a person has two extra copies of a chromosomal segment, this is known as a triplication (or sometimes as a Partial tetrasomy). Duplications and triplications can cause symptoms due to gain of extra copies of any genes contained within the additional chromosomal segment.

Inversions
Inversions arise when a chromosome breaks in two places, the intervening segment flips around and is then re-inserted into the 'gap.' Inversions are known either as paracentric, if the two breaks are in the same chromosomal arm, or as pericentric if the breaks occur in different arms of the same chromosome. Inversions would not usually cause symptoms in the carrier but can lead to fertility problems, or miscarriage. In the case of pericentric inversions there is also a risk for the birth of an affected baby with duplications and deletions of the two end segments of the chromosome involved. Carriers of paracentric inversions very rarely give birth to children with symptoms.

Isochromosomes and extra structurally abnormal chromosomes
Sometimes people carry an extra or supernumerary chromosome made up of part of one or more chromosomes. They will effectively carry a duplication of the material forming this extra chromosome. If the origin of the extra chromosome is unknown, it is referred to as an extra structurally abnormal chromosome or an extra marker chromosome. If the extra chromosome is made up of two copies of the same segment of a chromosome, this is called an isochromosome. When these extra chromosomes carry two copies of the same centromere, they are called isodicentric chromosomes.

Uniparental disomy
Normally one member of each pair of chromosomes is inherited from the father and the other from the mother. In rare cases, a trisomy in an early embryo can 'correct' itself by losing one of the extra chromosomes. If the remaining two chromosomes are inherited from the same parent, then this is called uniparental disomy (mUPD for inheritance from the mother and pUPD for inheritance from the father). UPD will only cause problems when the chromosome involved is susceptible to imprinting (i.e. the expression of the genes is parent-specific).

Inheritance patterns
Many chromosome abnormalities do not recur in families. However, since some abnormalities are due to a balanced chromosomal rearrangement in either parent, a child could display a chromosome disorder. Genetic advice should be sought to quantify the specific risks posed by individual chromosome abnormalities.

Prenatal diagnosis
Chorionic villus sampling (CVS) can be carried out usually around eleven to thirteen weeks of pregnancy and amniocentesis from around fifteen to seventeen weeks of pregnancy.

Medical text written October 2001 by Dr B Searle. Approved October 2001 by Professor M A Hultèn. Additional material on small Supernumerary Marker Chromosomes written July 2005 by Dr T Liehr, Institute of Human Genetics and Anthropology, Jena, Germany. Last updated October 2006 by Dr B Searle, Unique - the Rare Chromosome Support Group. Approved October 2006 by Professor M A Hultèn, University of Warwick, Coventry, UK.

UNIQUE

Unique - The Rare Chromosome Disorder Support Group
PO Box 2189
Caterham
CR3 5GN
Tel/Fax: 01883 330766 (answerphone 24 hours)
e-mail: info@rarechromo.org
Web: http://www.rarechromo.org

The Group is a National Registered Charity No. 1110661, established in 1984. It offers contact with families with an affected member who has the same rare chromosome disorder or who has similar symptoms or practical concerns, irrespective of specific chromosome disorder. It produces a comprehensive range of family-friendly, medically-verified leaflets on various rare chromosome disorders. There is a network of local contacts and Unique promotes awareness of rare chromosome disorders to the public and professional workers. It co-ordinates families to assist in research and has a password-protected discussion forum on the website for registered members. It also has a telephone translation and interpretation service (UK only). It publishes a newsletter three times a year and has information available, details on request. The Group has nearly 5,000 affected families and many professional workers as members worldwide.

Group details last updated May 2007.