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Genomics for the Practing OD

Lesley L. Walls, OD, MD, DOS

 

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INTRODUCTION

 

If you think you have seen dramatic technological changes in the last five years, just watch the next five!

Regarding the access to an incredible amount of genetic information it has been said that “even if we do not know and do not want to know, we now know that we can know”…and, “choosing not to know can be as heavy a burden as choosing to know”.

Scenario: two people meet and are considering whether or not to consider developing a relationship….so, they exchange hairs and say to each other, “call me if you think we should date again.

Picture a multi-handicapped person saying, “why would my parents choose to let nature take its course instead of having genetic testing with the technology available today?” Will the day come when we shall see a wrongful LIFE lawsuit?

“The human genome is becoming a substitute for the soul”….Alex Mauron

There have been several cartoons published regarding genomics and humorous situations. See Figure 1.

 

BizarroGenomics Cartoon WO Name

 

Figure 1: Genetics Cartoons

 

This course will instruct optometrists how to recognize genetic disorders like Smith-Magenis Syndrome, Diabetes, and cancers, and what can be done to prevent or treat these conditions, as appropriate.

There are several goals and objectives for this course on Genomics for the Practicing OD including:

 

 

CASE PRESENTATION: Vision Training Patient in the Pediatric Clinic with Smith-Magenis Syndrome

 

1 Family Portrait

 

Figure 2: A pediatric patient with Smith-Magenis Syndrome

(photo used with permission of the family)

The patient is a vision therapy patient in our clinic as a referral from a pediatrician for vision therapy for learning disorders and visually-related problems.  The patient had been previously diagnosed with ADHD and was receiving medication for it. Despite this, there were reportedly multiple developmental delays. According to her teacher, this patient had trouble focusing, with eye movements for reading, and with visual information processing.

Objectively, the patient was testing for visual-motor and non-motor perceptual delays. Deficits were found in all areas of the Test of Visual Perceptual Skills (TVPS), namely visual discrimination, memory, spatial relations, form constancy, sequential memory, figure-ground and visual closure. See Figure 3.

:TVPS-3.gifSmith-Magenis Syndrome #4.jpg

Figure 3: Test of Visual-Perceptual Skills (TVPS) and results

Source: http://www.bernell.com/product/3320/119

The Beery Visual-Motor Integration (VMI) test showed delays in copy forms accuracy and speed. See Figure 4.

 9 Drawing 1 7 VMI 8 Drawing 2

Figure 4: Beery Visual-Motor Integration (VMI) test and results

The patient was originally diagnosed as having Down Syndrome (Trisomy 21) but signs and symptoms during routine health care delivery by the pediatrician made for suspicions that there was another diagnosis rather than Down Syndrome.  The patient underwent genetic studies at a local laboratory to see if there could be any clarification of the diagnosis.  The various genetic studies are performed by a simple cotton-tipped applicator “cheek swab”.  In short, a cotton-tipped applicator is twirled between the cheek and upper teeth and gums and sent to the laboratory for analysis…similar to any police detective sending cells from under the fingernails of a victim who has scratched an assailant!  These cells are stable without refrigeration or other preservative care for years and years so no special care of the specimen is required.  In fact, the swab is simply placed in a standard envelope and mailed to the laboratory. The results are shown in Figure 5.

:Genome #1.jpg Smith-Magenis Syndrome #2.jpg

Figure 5: Cheek swab genetic testing results for this patient.

Note the deletion of short arm of Chromosome 17 Band p11.2

Genetic testing on the cells derived from the “cheek swab” confirmed that the patient has Smith-Magenis Syndrome.  The following is a brief overview of this syndrome:

 

 

The patient has very dedicated, well-off and loving parents who want only the best for their child and therefore they make certain that she is a faithful VT patient for her optometric care.  The patient also enjoys support from her pediatrician and from all her other health care professionals including a child psychologist.  All these health care professionals believe that her vision therapy program has helped tremendously as she demonstrated good, steady progress in motor skills and general behavior with the implementation of Vision Training. See Figure 6.

13 Golf15 Skiing

Figure 6: Smith-Magenis Syndrome patient demonstrates athletic skill despite mild intellectual disability, which is universal with this genetic disease.

The patient continues to do well and has only mild intellectual disability, so she is advancing in her schoolwork, and only a couple years behind what she should be for her age.

NOW IT IS TIME TO BEGIN THE PROCESS OF TRANSFERRING OLDER THINKING ABOUT GENETICS TO THE NEW THINKING ON GENOMICS.

 

 

I have “preached” POLYGENICS for Years!  This means that genetic predisposition + environmental insults  leads to the manifestation of virtually every disease and disorder that affects humankind,  In the past this was MOSTLY Speculation but now the Human Genome Project has proven the polygenic concept to be FACT!

In 1900 the three leading causes of death were pneumonia, tuberculosis and diarrhea. Today, the major causes of death are cancer, heart disease, stroke, injuries, lung disease, diabetes, influenza and kidney disease (in that order).  Public Health measures were largely responsible, with a minor role of newly invented medications, for this shift.  Life expectancy in 1900 was 46 years. Today in the United States, it approximates 80 years for women, and 75 years for men, with women outliving men on the average approximately five years. 

However, the theoretical maximum life expectancy is 120 years according to studies on normal cellular biology and physiology.  It appears quite possible that through control of the environment and better understanding and use of genetic information that life expectancy may continue to dramatically increase in the near future.  How long each of us, and our offspring, will live will depend more and more on understanding how the environment, including the genetic code of organisms that attack our bodies, interacts with each of our own individual genetic code composition and adversely affects cell and organ survival and effect total body life expectancy.

Just as we consider the health care practice at the time of our grandparents to have been primitive, so will our grandchildren feel about today’s optometry and the overall health care delivery to today’s population.  They will say, for instance, you mean the treatment for cancer was with poisons and not genetic manipulation to eliminate these abnormal cells called cancer!!!

In 2003 the 50th year celebration occurred for the discovery of the structure of DNA by Rosalind Franklin, James Watson and Francis Crick. See Figure 7.

V   DNA structure[1]

Figure 7: Double-helix structure of DNA

In the same year, the completion of the sequencing of all 3 billion base pairs of the human genome was completed.  Now the newly trained geneticists are undertaking a new basis for genetic research that will have far-reaching effects on the clinical practice of optometry, as well as all the other major health professions, with all the legal and ethical issues that will emerge as a result of these new discoveries.  The next big research steps will be the discovery of the function of all these sequenced genes and how they affect health and longevity.

It is interesting to note that each and every one of us, that is all human beings, have approximately 5-50 significant genetic defects.  The good news is that for the most part, these do not seem to be all that significant clinically.  However, these genetic abnormalities lead to shortening of the theoretical life expectancy by manifesting diseases such as diabetes, hypertension, cancer, auto-immune diseases, etc.

It is important to grasp the conceptual differences between the previous thinking in terms of “old genetics” versus “new genetics”.  In “old genetics” the thinking was that diseases are the result of a mutation in a single gene, a missing chromosome or an extra part of a chromosome.  In “new genetics” it is recognized that in actuality, that virtually all medical conditions, trauma excepted, have a genetic component that is multi-factorial, meaning that a number of genes interact with a number of environmental factors leading to disease(s).   The term for genetic predisposition for a disease and it then being activated by an environmental influence is termed “polygenic”.  In short, a genetic predisposition plus an environmental insult (viral infections, medications, ultraviolet light, food additives, artificial sweeteners, etc.) results in a specific disease being manifested.

Because many of these genetically predetermined diseases, triggered by an environmental interaction, affect the eye or are primarily manifested in the eye, this will definitely impact optometric practice in the future.

 

 

V how genes are linked to disease

Figure 8: Production of faulty amino acids, leading to defective proteins, by defective DNA and RNA. These genetic defects are often on many genes.

 

 

 

In Type 1 Diabetes Mellitus, there is a genetic predisposition due to a defect in the genetic apparatus.  If a person with this predisposition develops a certain viral infection, usually an influenza virus or the mumps or measles virus, this results in activation of a clone of “T” cells that should only neutralize and get rid of the virus.  However, in the genetically predisposed patient the result is an attack by these “T” cells on the Beta Cells of the Pancreas resulting in destruction of the Beta Cells.  The Beta Cells produce insulin and therefore with destruction of these cells there is a lack of insulin which results in the development of Diabetes Type 1.  

In this type of genetic disorder, it is theorized that genetic predisposition and environmental insult leads to virtually all the diseases and disorders that develop and affect all of mankind.