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.
In the domain of genetics, scientific knowledge has made many remarkable advances in recent years. In the last decade, the publication of the human genome, together with much molecular information existing at the time, has permitted genetic manipulation (GM) techniques to be used in the treatment of various diseases. In the past, doping and cheating in sports were enabled by advances in pharmacology and physiology. Now, advances in molecular genetics have given rise to the potential to improve various medical and non-medical human features. Choosing body type? Or maybe eye color? Or reducing the risk for common diseases like diabetes melliteus type 2, heart attack, etc, by manipulating the genetic risc factors? These questions seems a bit out of place in 2012. But who knows what will the future bring once the science evolves to the next level?
The most crucial step in any genetic consultation is that of establishing the diagnosis. If this is incorrect, then inappropriate and totally misleading information could be given, with potentially tragic consequences. Reaching a diagnosis in clinical genetics usually involves the three fundamental steps of any medical consultation: taking a history, carrying out an examination, and undertaking appropriate investigations. A full and accurate family history is a cornerstone in the whole genetic assessment and counseling process. Further information about the family and personal medical history often emerges at the clinic, when a full examination can be undertaken and appropriate investigations initiated. These can include chromosome and molecular studies as well as referral on to specialists in other fields, such as neurology and ophthalmology. It cannot be overemphasized that the quality of genetic counseling is dependent upon the availability of facilities that ensure an accurate diagnosis can be made.
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. 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. These techniques can be used when one partner is infertile, as in the case of Klinefelter syndrome and Turner syndrome, or simply to bypass the possibility that one or other partner will transmit his or her disadvantageous gene(s) to the baby. For some couples, the prospect of prenatal diagnosis followed by selective termination of pregnancy is unacceptable, whereas others view this as their only means of ensuring that they have healthy children.
Newborn screening programs have been introduced on a widespread basis for phenylketonuria, galactosemia, and congenital hypothyroidism. In all of these disorders early treatment can dramatically prevent the development of learning disability. To this group have been added hemoglobinopathies, cystic fibrosis, and medium-chain acyl-CoA dehydrogenase more recently, where knowledge of the condition and intervention is important but less dramatic in its benefits. Screening for several other disorders is carried out more selectively in different centers). In the United States, for example, all 50 states have a legal duty to provide screening to all newborns, at least for the first three conditions mentioned. In some states, (West Virginia, Montana, and South Dakota), screening is limited to these three conditions but at the other extreme up to 30 diseases are screened for (North Carolina and Oregon). In the United Kingdom, consideration is being given to screening for Pompe disease, maple syrup urine disease, tyrosinemia, congenital adrenal hyperplasia, isovaleric academia, glutaric aciduria type 1, and homocystinuria.
At the turn of the 19th century, it was discovered that fetal cells reach the maternal circulation, but confirmation that cell-free DNA of fetal origin (placentally derived) is present in the plasma of pregnant women was not made until 1997. This fact has now been exploited in clinical practice as early as 6 to 7 weeks of pregnancy to determine fetal sex by detection of Y-chromosome DNA, as well as fetal Rhesus D gene. Early determination of fetal sex is clinically useful in a pregnancy at risk of an X-linked recessive disorder, and also in congenital adrenal hyperplasia (see the following section). The problem with analyzing cell-free fetal DNA is one of isolation because maternal cell-free DNA constitutes about 95% of all the cell-free DNA in the maternal circulation. The absence of Y-chromosome DNA might indicate the fetus is female, or that the quantity of fetal DNA is very low. This is resolved by using real-time PCR to quantify the amount of fetal or total DNA present in plasma. Much effort is now focused on enriching fetal cells from maternal blood, which would make it possible to analyse the pure fetal genome because fetal red cells are nucleated; however, only about one fetal cell is present in 1 ml of maternal blood, and consequently current techniques are limited because of the scarcity of cells. If whole cells could be efficiently enriched, in theory fetal aneuploids could be detected using FISH, or other techniques based on allele ratios. Advances are taking place rapidly and non-invasive techniques are likely to become a reality in due course, and therefore change perceptions of prenatal diagnosis dramatically.