The genetics of CAH is very important - after all, it's the reason all of us are here either as sufferers or parents of sufferers of the condition. We've already explained that the 'Congenital' part of the name means 'from birth', so all sufferers are born with the condition, even if they have late onset varieties which don't show symptoms until later in life. CAH is an autosomal recessive condition. Autosomal simply means it affects both sexes equally, and recessive (or hidden) means that in order to inherit CAH you must have problems with the genetic material from both mother and father.
Chromosomes, Genes, DNA and all that stuff
All cells in the human body contain chromosomes. It is the chromosomes which govern genetic make-up and determine whether you have blue eyes, brown hair or conditions such as CAH. Each cell has twenty three pairs of chromosomes. Normally, each parent contributes one chromosome to each pairing, giving a total of forty six chromosomes. The chromosomes are made up of Deoxyribonucleic Acid, known as DNA for short. DNA is arranged in the well-known double helix shape.
DNA has thousands of segments, called genes. The sequence of bases in a gene tells the cell how to make specific proteins. Proteins determine the physical characteristics of living organisms. They also direct almost every aspect of the organism's construction, operation, and repair.
When the genes are damaged, or not properly repaired, problems can occur with how the genes work. These structural changes to genes are known as mutations which can lead to illnesses or disease. There are four types of mutations; deletion (where part of the DNA on a gene is lost), addition (where extra DNA is added), point mutation (where DNA is altered), and recombination (where DNA is swapped among different genes).
The different forms of CAH are caused by mutations on different genes, and even on different chromosomes.
As mentioned above, CAH is an autosomal recessive condition which means that faulty genes must be passed on by both parents. It is unlikely that both parents will have exactly the same mutation, and in this case, the less severe form of the condition is dominant. If only one faulty gene is passed on, the offspring will be an unaffected carrier.
So what is the likelihood of having child with CAH? There are five cases to consider:
1. Both Parents are Carriers
In this case there is a one in four (or 25%) chance that a child will be affected. This does not mean that if you have four children you are guaranteed to have only one child with CAH. The chances of having an affected child are exactly the same for each birth. In fact, you could have all four children with CAH - it's just very, very unlikely!
2. One Parent has CAH, one is a Carrier
Here, there is a two in four (or 50%) chance that a child will be affected. Similarly, there is a two in four (50%) chance that a child will be a carrier. It is certain (100%) that all children will either have CAH or be carriers.
3. One Parent has CAH, one is Unaffected
There is no (0%) chance that a child will be affected, but it is certain (100%) that all children will be unaffected carriers.
4. Both Parents have CAH
It is certain (100%) that all children will have CAH. This is the only outcome possible.
5. One Parent is a Carrier, one Parent is unaffected.
There is no (0%) chance that a child will be affected. There is a two in four (50%) chance that the child will be a carrier.
There is a sixth possible outcome which is by far the most common for the population as a whole. This is where both parents are unaffected, and of course in this case, none of their children will be affected or carriers.
Genetic Testing & Pre-Natal Treatment
Genetic testing isn't routinely used in the diagnosis of CAH. It can, however, be used for the purposes of family planning where the prospective parents are either carriers or sufferers of CAH. In this case, genetic counselling and testing may be offered prior to undertaking a new pregnancy. The testing compares abnormal adrenal gland genes to normal ones, and looks for differences which would indicate mutations. This means that only known abnormalities can be searched for, and indeed sometimes the searches are restricted to the most common mutations.
There is no pre-natal treatment that can 'cure' CAH. However, in the case of girls with virilising forms of CAH, there is a pre-natal treatment that can, in some cases, prevent or minimise the masculinisation of the genitals.
The treatment involves the mother-to-be starting a course of dexamethasone as soon as she knows she is pregnant (preferably before 6 weeks gestation). Once the pregnancy reaches 7-8 weeks gestation, it is now possible for the sex of the foetus to be determined with FISH analysis (fluorescent in situ hybridization), a test using fluorescent DNA probes on maternal blood. This is obviously a big advantage to mothers who have chosen to take dexamethasone treatment, as if the foetus is male, the medication can be stopped (slowly).
If the FISH test shows the baby is female, once the pregnancy reaches the 10th-15th week, a test can then be carried out to determine, whether she is affected by CAH. In the case of an affected girl, the course of dexamethasone is continued through the pregnancy but if she is unaffected, the treatment will have no benefits so (as with male the male foetus) the mother can be weaned off the treatment.
The pre-natal treatment of CAH is a relatively recent development, and many doctors still regard it as experimental. The long term effects of foetal exposure to dexamethasone are unknown and there are still concerns about the unknown risks of the treatment. Dexamethasone is a strong steroid and it can have nasty side-affects for the mother - excessive weight gain, moodiness, insomnia, acne and the development of severe stretch marks. Other potential problems such as high blood pressure mean that close monitoring of the mothers during pregnancy is essential.
The foetus is tested for CAH by either chorionic villus sampling (CVS) or amniocentesis. These tests in themselves carry risks. The chance of a miscarriage is slightly increased by having either of these tests.
A number of Support Group members have undergone pre-natal treatment and will be happy to discuss it further.