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This page gives you more information about the genetic background to Prader-Willi Syndrome (PWS), and the likelihood of you or any other members of your family having another child with PWS. The information reflects current knowledge, and therefore may change over time, as more research is carried out.
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In the vast majority of cases, the risk of having another child with PWS is very slight indeed. For example, a study in Australia of 144 families with a child with PWS found no recurrence. There were 266 living siblings of the PWS children, and they were all normal. |
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| Chromosome | Each cell in the body normally carries 46
chromosomes, numbered in pairs from 1 to 23. One chromosome of the pair is normally inherited from a person's mother, and the other from their father. Chromosomes contain genes: the hereditary factors which determine our body make-up. |
| Deletion | A small piece of material which is missing from a chromosome. |
| Disomy | Both chromosomes of a pair inherited from one parent, rather than (as is normal) one coming from the mother and one from the father. |
| Imprinted | Marked so that there are differences between maternal and paternal inheritance. |
| Maternal | Coming from the mother. |
| Translocation | an exchange of material between or within chromosomes, and can involve any chromosome, not just 15. |
Current research has shown that the set of symptoms known as Prader-Willi Syndrome result mainly from one of 4 different genetic abnormalities. These are:
Approximately, 60-70% of PWS cases are due to a de novo (or new) deletion on the chromosome 15 inherited from the father. There has been no known recurrence in any of these families. Theories have been put forward that this is due to accidental damage to the sperm or the egg at the time of conception, but none of these have yet been proved conclusively.
In about 25-30% of cases, Prader-Willi Syndrome can be the result of maternal disomy (two copies of chromosome 15 coming from the mother instead of one copy from each parent). These are included in the "non-deletion" cases. Once again there has not been a known recurrence of maternal disomy in any PWS family. However, the recurrence risk here is usually given as 0.4% for two reasons. Firstly, because some non-deletion PWS may be due to something other than disomy, and secondly because the risk of disomy increases a little with maternal age. Like the deletion cases, disomy is an accidental occurrence which occurs at meiosis (the process of cell division which takes place at the time of conception).
| Cytogenetics | The science concerned with the study of normal
and abnormal chromosomes, and of their behaviour. Cytogenetics is developing increasingly sophisticated techniques for studying the make-up of chromosomes on very microscopic levels. |
The very few families (less than 5%) which do have a high risk of having more than one child with PWS are those which carry a translocation involving chromosome 15. When the translocation is "balanced" (THIS NEEDS EXPLAINING) then it can pass from one generation to another with no harmful effect, but it is sometimes possible for it to be passed on in an "unbalanced" form, and a deletion can result. When a deletion is the result of a translocation or structural rearrangement involving chromosome 15, then the recurrence risk can be high. The actual risk in individual families depends upon the rearrangement which they carry. Fortunately however, cytogenetic studies can identify these families so that they can receive appropriate advice.
Chromosome 15 is almost unique in that it carries an imprinted region. This means that it is marked so that the copy (or homologue) inherited from the mother behaves differently from the one which comes from the father. Imprinting explains why the deletions which occur in Prader- Willi syndrome always arise in the paternal copy of chromosome 15 and why disomy always comes from the mother. Very occasionally an error occurs in the the setting of the imprint and Prader-Willi syndrome can result.
Research is continuing into whether there are any differences in development between those who have a deletion and those who do not. At the present time there appears to be little difference, except that those who have a deletion have the more typical PWS facial appearance, with lighter hair than the rest of their family and light blue/grey eyes. Those without the deletion show more heterogeneous characteristics.
Dr. Tessa Webb of the Department of Clinical Genetics at Birmingham Maternity Hospital has personally studied over 60 families in the UK. Only one of these families has had more than one person with PWS, and this family had a 15:22 translocation which was passed on from one generation to another.
If you are in any doubt about whether to have more children, or whether the condition will be passed on through your other children, ask your paediatrician or medical specialist to refer you to a genetic counselling centre, where blood tests can be carried out on you and your child to determine how the chromosomes have been affected, and if there are any risks in having more children. Usually, you can arrange for samples of your blood to be taken at your local GP practice or hospital.
Taking blood samples can also aid initial diagnosis of PWS. Chromosomes and DNA are both obtained from white blood cells. It is necessary to have blood samples from both parents as well as the child with PWS for several reasons.
The PWSA (UK) is very grateful to Dr. Tessa Webb for her help in producing this leaflet, and to Dr. Bernard Laurance, Prof. Victor Dubowitz and Dr. Jenny Morton for their suggestions and comments. |
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