CHAPTER 17 Genetic Counseling
Any couple that has had a child with a serious abnormality must inevitably reflect on why this happened and whether any child(ren) they choose to have in future might be similarly affected. Similarly, individuals with a family history of a serious disorder are likely to be concerned that they could either develop the disorder or transmit it to future generations. They are also very concerned about the risk that their normal children might transmit the condition to their offspring. For all those affected by a genetic condition that is serious to them, great sensitivity is needed in communication. Just a few words spoken with genuine caring concern can put patients at ease and allow a meaningful session to proceed; just a few careless words that make light of a serious situation can damage communication irrevocably. The importance of confidence and trust in the relationship between patient and health professional must never be underestimated. In the commercial world the same applies—confidence is a prerequisite for business contracts (between both parties).
Definition
It is also agreed that genetic counseling should include a strong communicative and supportive element, so that those who seek information are able to reach their own fully informed decisions without undue pressure or stress (Box 17.1).
Establishing the Diagnosis
Even when a firm diagnosis has been made, problems can arise if the disorder in question shows etiological heterogeneity. Common examples include hearing loss and non-specific mental retardation, both of which can be caused by either environmental or genetic factors. In these situations empirical risks can be used (p. 346), although these are not as satisfactory as risks based on a precise and specific diagnosis.
A disorder is said to show genetic heterogeneity if it can be caused by more than one genetic mechanism (p. 346). Many such disorders are recognized, and counseling can be extremely difficult if the heterogeneity extends to different modes of inheritance. Commonly encountered examples include the various forms of Ehlers-Danlos syndrome (Figure 17.1), Charcot-Marie-Tooth disease (p. 296), and retinitis pigmentosa, all of which can show autosomal dominant, autosomal recessive, and X-linked recessive inheritance (Table 17.1). Fortunately, progress in molecular genetics is providing solutions to many of these problems. For example, mutations in the gene that codes for rhodopsin, a retinal pigment protein, are found in approximately 30% of families showing autosomal dominant inheritance of retinitis pigmentosa (Figure 17.2) and the molecular basis of the most common forms of Charcot-Marie-Tooth disease (type 1), also known as hereditary motor and sensory neuropathy, is now understood (p. 296).
Table 17.1 Hereditary Disorders that can Show Different Patterns of Inheritance
| Disorder | Inheritance Patterns |
|---|---|
| Cerebellar ataxia | AD, AR |
| Charcot-Marie-Tooth disease | AD, AR, XR |
| Congenital cataract | AD, AR, XR |
| Ehlers-Danlos syndrome | AD, AR, XR |
| Ichthyosis | AD, AR, XR |
| Microcephaly | AD, AR |
| Polycystic kidney disease | AD, AR |
| Retinitis pigmentosa | AD, AR, XR, M |
| Sensorineural hearing loss | AD, AR, XR, M |
AD, Autosomal dominant; AR, autosomal recessive; XR, X-linked recessive; M, mitochondrial.
Calculating and Presenting the Risk
In some counseling situations, calculation of the recurrence risk is relatively straightforward and requires little more than a reasonable knowledge of mendelian inheritance. However, many factors, such as delayed age of onset, reduced penetrance, and the use of linked DNA markers, can result in the calculation becoming much more complex. The theoretical aspects of risk calculation are considered in more detail in Chapter 22.
Quantification—The Numerical Value of a Risk
Most prospective parents will be familiar to some degree with the concept of risk, but not everyone is comfortable with probability theory and the alternative ways of expressing risk, such as in the form of odds or as a percentage. Thus, for example, a risk of 1 in 4 can be presented as an odds ratio of 3 to 1 against, or numerically as 25%. Consistency and clarity are important if confusion is to be avoided. It is also essential to emphasize that a risk applies to each pregnancy and that chance does not have a memory. For example, that parents have just had a child with an autosomal recessive disorder (recurrence risk of 1 in 4) does not mean that their next three children will be unaffected. A useful analogy is that of the tossed coin that cannot be expected to remember whether it landed heads or tails at the last throw and cannot therefore be expected to know what it should do at the next throw.
Discussing the Options
Having established the diagnosis and discussed the risk of occurrence/recurrence, the counselor is then obliged to ensure that the consultands are provided with all of the information necessary for them to make their own informed decisions. This should include details of all the choices open to them. For example, if relevant, the availability of prenatal diagnosis should be discussed, together with details of the techniques, limitations and risks associated with the various methods employed (see Chapter 21). Mention will sometimes be made of other reproductive options. These can include alternative approaches to conception, such as artificial insemination using donor sperm, the use of donor ova and preimplantation genetic diagnosis (p. 335
