Advocacy groups for patients with genetic disorders

The characteristics of genetic disorders call for complex and comprehensive plan of management.  It requires the active participation of the family (immediate and extended), healthcare providers (specialists in various disciplines), basic scientists and support groups. 

Advocacy and support groups play an important role in ensuring that patients and families receive the required the services. Genetic Alliance is an organization that “serves as an open space for sharing valuable resources, creative tools, and innovative programs.”  http://www.geneticalliance.org/about. 

The Genetic Alliance provides a “Mandate for Quality Genetic Services” worthy of review.

http://www.geneticalliance.org/principles.

An advocacy group such as the Genetic Alliance could be a valuable resource for patients and families with genetic disorders.  Such a group should be one that forms a partnership with various facilities and groups and an information portal that could help patients and families with information required for the diagnosis, therapy and management.

Who will take the initiative to start such a resource?  It would be individuals familiar with the technical and scientific aspects of genetic disorders and familiar with the needs of patients and families.  That would be interested genetic counselors, clinicians, basic scientists and families of patients with genetic disorders.  It is worth reviewing the history of the Genetic Alliance http://www.geneticalliance.org/about/history.

Prerequisites for effective genetic counseling.

The definition of genetic counseling is:

 

Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates the following: Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. Education about inheritance, testing, management, prevention, resources and research. Counseling to promote informed choices and adaptation to the risk or condition (REF: National Society of Genetic Counselors' Definition Task Force, Resta R,Biesecker BB, Bennett RL, Blum S, Hahn SE, Strecker MN, Williams JL. A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report. J Genet Couns. 2006 Apr;15(2):77-83).

 

The most important requirement for genetic counseling is an accurate diagnosis of the disorder. Accurate diagnosis depends on the skill and service of clinicians trained in clinical genetics, results of diagnostic tests performed in laboratories equipped to perform and interpret the required assays and obtaining a detailed family history (pedigree). 

 

For instance, in the case of multiple miscarriages – it is the obstetrician or gynecologist who has to identify the patient who could benefit from genetic testing.  Couples with two or more spontaneous miscarriages are considered at a higher risk of being a carrier of a balanced translocation and therefore at risk of a fetus with an unbalanced karyotype.  This risk would be higher if there are family members who have experienced spontaneous miscarriages or other clinical indications of chromosomal abnormality (infertility, neonatal deaths, congenital abnormalities and developmental delay).  Use of appropriate words, language and techniques are essential to obtain critical information.  There are a number of reasons for miscarriages.  Chromosome abnormalities is only one of them (http://www.aafp.org/afp/2005/1001/p1243.html).  Genetics counselors have to develop skills to obtain as much information as possible from the couple to provide the most accurate information to help the couple. An important task of genetic counselors is to obtain an informative family history (pedigree).  Unless an obstetrician or gynecologist refers a patient to a genetic counselor this essential step of obtaining a family history may be missed during the clinical work up.

 

Access to laboratories that can provide a reliable and accurate report is important for effective genetic counseling.  Genetic counselors play a major role in evaluating the standards of laboratories. 

 

It is critical that the couple understands the results to act upon.  Genetic counselors have to be comfortable with the scientific information to convey the information to the couple and ensure that the couple understands the information provided to them. A variety of teaching tools may be required to adequately educate the family on the genetic basis, recurrence risk, management etc.

 

Spontaneous abortion is used as an example here; the scenario could be more complicated for other disorders.  There are a number of disorders with significant similarities in phenotype but with different genetic basis (different genes as well as different patterns of inheritances).  In some instances the skill of a well trained clinician, to make a clinical diagnosis, is imperative before a laboratory test is performed to make or confirm the diagnosis.  This is especially important as many laboratory investigations for genetic disorders are expensive.  Therefore the most informative laboratory testing should be considered based on the clinical diagnosis.

 

Once a diagnosis has been confirmed, management may involve a variety of options, depending on the situation.  In the case of prenatal diagnosis the decision may be termination of pregnancy or continuation of pregnancy (that may be of a high risk nature).  In the case of post-natally diagnosed cases, the needs may be one of many (surgical, clinical, nutritional/dietary, physical therapy, educational etc).

 

When establishing a genetic counseling service, the question should be – are the pre-requisites in place for adequate genetic counseling? 

 

Are there well trained clinicians who can identify patients/families who can benefit from genetic counseling?

 

Do clinicians take detailed family histories?  If not, do clinicians refer patients to genetic counselors to obtained family histories as well as co-ordinate testing?

 

Are laboratories that can provide reliable testing available?

 

If applicable, do clinicians explain the genetic basis of a disorder to the patients?  If not do they refer the patients to trained genetic counselors?

 

Are there adequate facilities for safe termination of pregnancy?  Are there adequate facilities for monitoring high risk pregnancy and deliveries?

 

Are there adequate facilities for clinical and therapeutic management for post-natally diagnosed cases?  Are there support services available for patients and their families?

 

 

 Optimal genetic counseling is a relatively complex process that requires a variety of facilities.  Identifying these facilities or developing them is critical before genetic counseling is offered as a service.

Parent support groups for genetic disorders

Parent support groups play an important role in a variety of capacities for patients, families, healthcare professionals and researchers. (REF:  J G Hall.  The role of patient advocacy/parent support group.  South African Medical Journal Vol 103(12):1020-1022, Dec.2013.  http://www.samj.org.za/index.php/samj/article/view/6976/5581

The Foundation for Prader Willi Research (http://www.fpwr.org/) is a well established support group.

MERD India is a parent support group in India   http://www.merdindia.com/index.html.  I have had the privilege of meeting Mr. Vikas Bhatis, a founding Member of MERD India.  Students in the field of Genetic Counseling can gain a great deal on the perspective of a member of a family at risk of a genetic disorder.

Considering the valuable role of such organizations, what role does the healthcare professional play in encouraging parents to start a support group?  Professionals in the field of genetics, in particular, genetic counselors can be both catalysts as well as activists in helping families start support groups, provide technical guidance as well as help with operational needs including fund raising and grant writing.   A review of the Prader Willi Research Foundation web site is educational to understand the potential of such support groups.  Check out the Board of Directors of the PWRF to see how the members are all parents of children with PWS.    The range of information in the websites is very broad. There is educational material for all including families of children with PWS, students in the field of genetics, scientists and researchers as well as for any individual interested in learning about the various aspects of PWS.

Social media aiding in the diagnosis of genetic disorders

Can parents and families help professionals in the diagnosis of genetic conditions?  There is ample material available for the diagnosis of “relatively common” conditions such as Down syndrome.  This however, is not so in the case of rare disorders.  The use of social media in identifying additional cases  with rare mutations is illustrated in the article by parents of two patients with mutations in the enzyme N-glycanase 1 (NGLY1) (REF:  Might , M and Wilsey, M  The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated.  Genetics in Medicine 16:736-737, 2014.  http://www.nature.com/gim/journal/v16/n10/pdf/gim201423a.pdf). In this article the authors used social media to help identify additional patients with the mutation detected by whole-genome, whole-exome or standard Sanger sequencing.  Patients were linked together after parents, physicians, or scientists working on isolated cases searched online for “NGLY1.” They found a blog post describing the disorder written by the parents of the first confirmed patient (http://matt.might.net/articles/my-sonskiller).

The following points are quoted from the article:

• Share early, share often. Collaborate across institutions, disciplines, patients, and parents. We recognize that this is easier said than done, but it is essential. Share data. Share negative results. For findings too small to be publishable, turn to the Web and publish them in short blog posts. Get the information out there. When Stanford and Baylor did whole-genome sequencing in the Fall of 2011 on an NGLY1 patient, they produced eight candidate genes (including NGLY1) to explain the phenotype. Stanford and Baylor shared their list of variant candidates quickly. It was a dialogue with clinicians, other researchers, parents, and bioinformatics experts. The teams triaged the list and worked systematically to close certain doors. Stanford and Baylor initially thought another gene was the main culprit, but functional work did not support this. Both teams continued to refine until NGLY1 was confirmed via functional assays. The lesson is that genetics is an iterative process.

• Balance the bottom-up with the top-down. We recognize that much of science happens “bottom-up,” with open ended investigations uncovering basic truths. Balance this approach with “top-down,” measurable goals that are grounded in patient’s needs. We know science takes random turns and there will be setbacks and pitfalls, but no successful business has been built without measurable goals and targeted objectives. Strike a balance.

• Move fast and break things. This motto is common in Silicon Valley, but has been popularized by Facebook CEO Mark Zuckerberg. Genetics, like any branch of medicine, is justly conservative when it comes to patients (“Do no harm”). We do not suggest that you should be less thorough or loosen protocols. We simply suggest that you take risks to make discoveries, even if ideas or assays fail along the way. Failure is good. We can all build upon those failures if we share.

The authors conclude with the following:

In order to diagnose patients, we must admit the limitations of our medical knowledge. Sometimes the best ideas come from individuals “outside the box” (i.e., patients and parents). Pay special attention to the smallest details (e.g., lack of tear production); sometimes the least likely gene candidate is the answer. Last but not least, thank you. What you do is truly remarkable. When you have a bad day in the clinic or the laboratory, please remember that there are patients and parents out there who you do not know and who are dreaming of finding you, supporting you, and counting on you. 

Can a similar scenario operate in the diagnosis of genetic disorders in a healthcare system in which there is a dearth of trained professionals required for the diagnosis of genetic disorders?  Could social media help to identify healthcare professionals in an healthcare system who can help in the process of diagnosis and management?  One would think so.

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.