Maternal serum screening and genetic counseling

The earliest protocol for maternal serum screening to detect chromosomal abnormalities in the fetus was screening during the second trimester measuring alpha feto-protein, human chorionic gonadotrophin and estriol (detects about 69% of Down syndrome). The next generation of this screening protocol was the quad screen – which added inhibin A to the substances screened for (detects 81% of Down syndrome). The next step in the evolution of serum screening was the first trimester screening which included measuring pregnancy-associated plasma protein-A (PAPP-A) and Human chorionic gonadotropin (hCG) and measuring nuchal translucency by ultrasound. While the detection rate of second trimester screening was 81%, first trimester screening can detect 82-87% of Down syndrome. Combining the first and second trimester screening increases the detection rate to 90-95%.
What does this evolution of screening mean for the consumer/patient? To make an informed decision on whether to avail of the testing, the patient has to understand the benefits and limitations of each of them. Timing of the testing (first trimester vs second trimester) is one factor to be considered. The detection rate of the various protocols is another. The limitations of each of the protocols is yet another (second trimester screening can detect neural tube defects whereas first trimester screening cannot). The highest detection rate is obtained by combining first and second trimester screening. However the patient has to wait until results of the second trimester screening is available for calculating the risk for Down syndrome.
If a patient decides to have the screening and already in the second trimester, there is no difficulty in decision making since the choice is limited; only second trimester is possible. However if the patient is in the first trimester, deciding between first trimester and combing first and second trimester screening can be difficult, particularly if the first trimester results are abnormal. Counseling prior to participating in the screening program is vital in ensuring that the patient is informed about its sensitivity and about the meaning of false positives and false negatives. Even in developed countries, real counseling is often conducted only after a positive serum screening result is made and an invasive procedure (amniocentesis or chorionic villus sampling) is discussed as the next level of testing. In developing countries where serum screening is now being made available, are patients provided with appropriate counseling prior to the screening? When the screening results are positive for a chromosome abnormality, are there adequate facilities for follow up invasive procedures and cytogenetics studies?
As always as soon as new scientific information is available, it is applied in the clinical arena, irrespective of how complex the information is for the patient to understand or how complicated the logistics are for reaping the full benefit of the information. The article “First-trimester screening: dealing with the fall out” (Fisher J in Prenatal Diagnosis 31:46-49, 2011) discusses parental anxiety that is associated with prenatal screening procedures such as ultrasonography and the need to have facilities available to deal with this anxiety. An important facility is the the availability f trained professionals who have the skills to help patients make an informed decision as well as help deal with their anxiety.

Genetic counseling and the “family” in India

The discipline of genetic counseling was developed to empower families to make decisions related to reproduction when faced with a risk of a genetic disorder. In these countries (most of them being developed countries) for decisions related to health and reproduction, the patient and family are defined as the affected individual and the partners respectively. Involving other members of the family in the decision making process is a choice made by these primary individuals. This basic tenant may not be the case in a country like India. For example when evaluating repeated spontaneous abortions, in many instances, the female patient is accompanied not by her male partner, but by her mother or her partner’s mother. Sensitive personal information, which in the western nations would be considered confidential and meant only for the patient or the couple is expected to be shared with those individuals accompanying the patient. Is this appropriate? If the patient or couple are eventually going to include these individuals in the decision making process – maybe it is appropriate for the medical personnel (in this case the genetic counselor) to involve these members of the family in this process from the very beginning and all through the process. This inclusion will ensure that these members of the family are receiving the required important information first hand from a trained professional. The couple should be informed on the nature of information that will be included in the counseling session and offered the opportunity to decide who is included in the counseling session. Developing a protocol for genetic counseling which includes educating the patient/couple on the nature of information that would be provided and offering them the opportunity of selecting the members of the family they would like included during the session should be an important part of this protocol. As a first step towards developing such a protocol a project should be undertaken to study the issue of including family members during genetic counseling.

Access to information and the capability of follow through in clinical genetics

The access of knowledge but inability to follow through – an important issue to be addressed when developing clinical genetic services in a developing nation.

Technological globalization with satellite television and internet has helped citizens in developing nations to gain access to information effortlessly with minimal resources. What is the value of knowledge in the absence of facilities to benefit from the knowledge? This is an aspect relevant to practically all fields, resulting in differing levels of frustration depending on the situation. In clinical genetics, physicians provide patients and families with a diagnosis. The patients and families gain additional information from the internet and are anxious to follow through on the information. A realistic understanding of utilizing the information to their advantage and the accessibility to facilities are the logical next steps. In a developing nation who do these families turn to for help in understanding if the information is applicable to them and if it is applicable how to take the next step? This is a valuable service that can be provided by trained genetic counselors.

Training genetic counselors

Training of genetic counselors may be broadly classified into basic science, genetics, clinical, laboratory, counseling, communication, sociology and cultural aspects. A basic knowledge in biochemistry, physiology and embryology is required for the understanding of the basis of genetic disorders and congenital malformations. Principles of genetics (modes of inheritance, calculating recurrence risks, variable penetrance and expression), and cell biology (structure and function of DNA, RNA and protein, transcription, translation) are important for understanding the basis of the disorders and in conveying this information to patients/families.

Genetic counselors should be knowledgeable on the clinical aspects of the most frequently encountered genetic disorders, their genetics and clinical management. This includes, cytogenetic, biochemical disorders, and adult disorders with a genetic or a multifactorial etiology.

Basic knowledge of the laboratory aspects related to cytogenetics, biochemical and molecular genetic testing is valuable in explaining them and their limitations to the patients.

Equipping genetic counselors with counseling techniques, communication skills and developing an appreciation for the social and cultural aspects of the population to be served are all valuable to successful genetic counseling.

Faculty members may be drawn from the existing faculty in the medical colleges and other departments in the teaching institutions. The curriculum should be designed with special focus on how the information will be useful in understanding and managing genetic disorders.

The importance of access to literature cannot be emphasized enough. Being a relatively new discipline, there is constant addition of information to the existing literature. The faculty and students should have access to the most current literature.

Internships in a variety of clinics where genetic counseling is conducted is invaluable for the training of genetic counselors. Supervised counseling by the trainees is also important for their professional development.

Role of genetic counselors

The role of a genetic counselor may vary and depends on the situation in which they function. Their activities include utilizing their skill in helping the clinician in the diagnosis and management of patients/families with a genetic disorder or a history of a genetic disorder. Another important activity of genetic counselors is to educate the patient/family on the various aspects of the genetic disorder in their family so that they can make informed decisions. The accurate diagnosis of a genetic disorder requires obtaining a detailed family history, review of the literature and use of specialized (sometimes relatively rare) laboratory testing. Many of these activities (including identifying a lab that performs the testing and making arrangements for these testing) can be time consuming. Genetic counselors can help physicians with these times consuming activities, thereby relieving the physicians to utilize their time more efficiently.

Conveying the diagnosis, results and risk figures in a manner that the patient/family fully understands can be challenging at times. This is because of the wide range of educational and socio-economic background of the patients/families. The genetic counselors can once again help the physicians during this process so that the physicians can use their time performing tasks that are more clinically relevant.

How the responsibilities of a genetic counselor are set up in a particular clinic/center is of course left to the discretion of the clinician responsible. Since genetic disorders are dealt with in a clinical setting, it is not unusual for patients to expect clinicians to be the individual they interact with. The clinician should discuss the role of the genetic counselor and inform the patient that the activities of the genetic counselor in the process of genetic evaluation and management are important and beneficial in the overall process. The clinician should also reassure the patient that the genetic counselor is a team member and discusses all the information with the physician so that the physician can arrive at the appropriate diagnosis and course of management - both of which are the ultimate goals for the patient/family.

Genetic counseling – the counselor’s perspective

Genetic counseling encompasses providing the patient/family with information essential for making an informed decision. How does one evaluate the efficacy of counseling? Genetic counseling should be non directive in that counselors should not impose their values or decisions on the patients and families they counsel. Therefore in evaluating a counseling situation, it would not be appropriate to assume a certain outcome and then determine if that is what is achieved. One method of determining the success of counseling would be to evaluate how much the patient/family understood and retained the information provided during the counseling session. Many factors could influence the patients understanding of the information provided. One of them is the educational background. Another important factor is the emotional status of the patient at the time they are provided with the information, which in turn would depend on the clinical situation they are involved in. Yet another factor would be the social and cultural background of the patient/family. These important factors have to be controlled for when studying the efficacy of genetic counseling.

Genetic consult – from a patient’s perspective.

What are the expectations of a patient/family going into a genetic consult? What is the objective of the genetic professional going into a genetic consult? It is very important that the genetic professional makes every effort to learn about the patient/family’s expectation about how the session is going to help them. Asking the patient to provide information on their expectations in addition to family history and clinical history is valuable. In return the genetic professional has the responsibility to provide the patient with realistic expectations.
An example is expectations prior to prenatal diagnosis. It is not unusual that the couple may be under the impression that the procedure guarantees “a perfect baby”. They have to be counseled on the limitations of the procedure in terms of what it can and cannot diagnose and that there are a number of disorders that cannot be diagnosed by the tests being performed. Patients have to understand that there still exists the possibility of residual risk of a child with a genetic abnormality or congenital abnormality after a normal result.
What is a patient’s understanding of drawing blood for karyotyping? A potential misconception is that treatment to change the phenotype is possible. It is important that the family understands that karyotyping is a diagnostic modality and one that is useful in estimating recurrence risk and not one which will change the observed phenotype.
Counseling prior to screening tests such as maternal serum screening is extremely valuable. Patients have to be educated that screening tests have false positives and false negatives and that follow up studies may be warranted. If they are uncomfortable with the possibility of false negative, they should be offered the option of more definitive tests such as chorioic villus sampling or amniocentesis.
Every so often results of tests are ambiguous. This is particularly the case of aCGH in which the clinical significance of some copy number variations is impossible. Patients have to be prepared for such uncertainties prior to embarking on the investigation.