1. SECTIONS:
2. preface & acknowledgements
3. genetics at a glance
4. contacts, support & testing
5. testing & pregnancy
6. newborn screening
7. cancer in the family
8. cardiovascular conditions
9. chromosomal conditions
10. clotting & bleeding conditions
11. cystic fibrosis
12. diabetes
13. fragile X syndrome and other causes of developmental delay
14. haemoglobinopathies
15. hereditary haemochromatosis
16. neurofibromatosis
17. neurological conditions
18. psychiatric conditions
19. genetics in practice
20. emerging genetic technologies
21. glossary

Changes in chromosomal structure

 

1. Changes in chromosomal structure are a result of chromosome breakage and rearrangement of some of the chromosomal material.
2. Structural rearrangements include translocations, inversions, deletions and other uncommon changes.
3. The two types of translocations are reciprocal and Robertsonian translocation.

 

Reciprocal translocations

1. Reciprocal translocations arise when an exchange of chromosomal material takes place between two different chromosomes.
2. This is the most common type of translocation, with an incidence of around 1 in 500 in the general
   population.
3. Reciprocal translocations may be either inherited (familial) or sporadic (de novo) where neither parent
   has the rearrangement. The recurrence risks (see below) vary in each type and depend on the nature of the translocation itself.
4. When there is no net gain or loss of genetic material, the rearrangement is said to be ‘balanced’.
5. Balanced translocations in an individual do not usually impact on growth or development, but can have
   reproductive effects due to inheritance of unbalanced forms of the translocation in the conceptus.

 

Recurrence risk

1. If a couple has a pregnancy with a sporadic (de novo) reciprocal translocation, the recurrence risk in another pregnancy for a sporadic reciprocal translation is extremely low.
2. The major risk for couples where one partner has a ‘balanced’ reciprocal translocation is either miscarriage or an affected liveborn, both due to inheriting the translocation in an unbalanced form. The recurrence risk for this couple may be up to 20%.
3. Some couples with a balanced translocation may be at very low risk of having a liveborn affected child because the unbalanced forms are invariably lethal and end in miscarriage or fetal death.

 

Robertsonian translocations

1. Robertsonian translocations occur in around 1 in 1,000 live births.
2. This type of translocation involves acrocentric chromosomes (13, 14, 15, 21 and 22).
3. The long arm of one chromosome fuses to the long arm of another chromosome, with loss of both short arms producing a longer chromosome, eg fusion between chromosomes 14 and 21.
4. In Robertsonian translocations both long arms of the chromosomes are still present, only fused together. The loss of the short arms has no impact as they contain non-essential DNA (ie no functional genetic material).
5. When there is no change in the total amount of functional genetic material, the Robertsonian translocation is described as ‘balanced’, even though there are only 45 chromosomes.
6. Balanced Robertsonian translocations in an individual do not usually impact on growth or development, but can have reproductive effects, as with reciprocal translocations, when the fetus receives the translocation in an unbalanced form.
7. Approximately 5% of cases of Down syndrome are due to an unbalanced Robertsonian translocation involving chromosome 21, with 46 chromosomes present.
8. Approximately 1 to 2% of cases of Down syndrome are due to inheriting an unbalanced Robertsonian translocation from a parent who is carrier of a balanced translocation.

 

Recurrence risk

1. If a couple has a pregnancy with a sporadic (de novo) unbalanced Robertsonian translocation, the recurrence risk in another pregnancy for a sporadic Robertsonian translocation is extremely low.
2. The major risk for couples where one partner has a balanced Robertsonian translocation is either miscarriage or an affected liveborn due to having inherited the translocation in an unbalanced form. The recurrence risk varies with the chromosomes involved. This couple will also be capable of conceiving normal and carrier offspring.

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