Don’t Blame Mother

©Bryan Sikora/Shutterstock

It shouldn’t be about blame, of course, in the first place. But, what is incomplete about the diagram below?

When a child is diagnosed with an X-linked recessive disorder, the inheritance pattern is often illustrated with a diagram like this one. Notice where the buck stops.

What parents might be shown

What could going back one more previous generation reveal? There are (at least) five possibilities.

First, let’s be clear, the mother might not be a carrier to begin with.

There might not have been a genetic alteration previous to the diagnosed child; the mutation (to use the “m-word”) just sprang up suddenly in the early embryotic divisions of the affected fetus, causing the disorder. In that case, the mother is not a carrier. However, this diagram might be used to explain how things usually work, even when the mother has not been  identified as a carrier through genetic testing.

A second possibility: the mother does have the mutation, but only in some of her ova, or egg cells. She, also, would not be identified as a carrier because the mutation does not affect the DNA in her entire body. A blood test would not reveal the mosaicism (that means some egg cells are affected, others are not) because the DNA in the rest of her body, and many of her ova, does not code for the disorder.

Further possibilities occur when the mother is identified by genetic testing as a carrier in the usual sense (each pregnancy having 25% chance of an affected son, 25% chance of a carrier daughter, 50% chance of an unaffected child, as illustrated in the diagram). But how does she happen to be a carrier?

That brings us to the third possibility: A “spontaneous mutation” occurred making the mother a carrier without previous genetic history in the family. It is often estimated that in some X-linked recessive disorders, around 30% of affected pregnancies result from such “out of the blue” genetic changes.

©Voronin76/Shutterstock

Fourth possibility: She was a carrier daughter of a carrier mother. The damaged gene “runs in the family,” although there may never have been an affected son born to anyone before this. Of course, everything said above about the mother, can also be applied in the grandmother’s case.

Fifth possibility: Because a daughter gets an X chromosome from each parent, the mother could have inherited the mutation from her father! Gosh, that’s something you seldom hear!

©Lisa F. Young/Shutterstock

But yes, in spermatogenesis, mutations occur. If the sperm carrying an X chromosome with an altered gene fertilizes the egg, well, there you have it, a new carrier daughter. No one will suspect, there will be no reason to test, until an affected grandchild of the new carrier’s father is born and begins to manifest symptoms of a disorder that no one knew ran in the family…because it didn’t.

I’m not sure why knowledge of these different scenarios should affect the burden of guilt felt by many mothers who are implicated in genetic inheritance patterns, but I strongly suspect that it does. After all, guilt is an emotion and therefore irrational to begin with. It is easy to say, “It’s nobody’s fault.” But in the case of X-linked recessive disorders, given the way the inheritance has been diagrammed for generations, is it any wonder so many moms feel it all came from them?

Is it stigmatizing to be identified as a carrier of a genetic disorder?

When a disorder “runs in the family,” it might be a source of stigma. Whether it is or not, all depends.

© onder turan

Being stigmatized, or marked as different and undesirable, involves the loss of social standing. One is marked as being less than others and is aware of being so marked.

© Ioannis Pantzi

Usually, there are negative stereotypes associated with stigmatized groups. The classic  work on the subject is Stigma: Notes on the Management of Spoiled Identity (1963), by  Erving Goffman, in which stigma is described as tainting and discrediting. Stigma is  defined by a social environment because it results from the way others see us. To the  degree that we “buy into” their judgments, shame is also attached to conditions that are  stigmatized.

The opposite of stigma can be the healthy pride that comes from feeling respected by others. Whether others respect us can depend upon how well we are fulfilling our social roles as defined by our surrounding culture. Health and beauty are generally respected and admired. In reproductive matters, producing offspring, especially males, is a source of pride of accomplishment for men and women in many societies. For any particular culture, the more social standing that results from producing children, the more likely it will be that having no children, or imperfect children, will result in social stigma.

© cofkocof

We can regulate stigmatization by controlling our immediate social environment. The people we associate with, the viewpoints we read or listen to, and the information we divulge can all affect the number of negative evaluations coming at us.

For more information on stigma & health:  http://www.stigmaconference.nih.gov/papers.html

© 2011  Jane Belland Karwoski

Blaming the Victim–Genetically

This autumn [2010] sees the start of the screening of Division 1 student athletes for “sickle cell trait,” as mandated by the National Collegiate Athletic Association.  From 2000 to 2009, seven college football players who were genetic carriers of sickle cell anemia have died during extreme workouts (see http://web1.ncaa.org/web_files/health_safety/SickleCellTraitforCoaches.pdf where the workouts are referred to as “conditioning activities”).

These student athletes did not have sickle cell anemia. A person must have two matching genes, both coding for altered hemoglobin, to have the disease. Having only one such gene, the students who died were not afflicted with sickle cell disease.

The Facts:

• “Sickle cell trait” is not a disease. It is an unusual case of a label being applied to the situation of having one abnormal allele when two are needed to have the genetic disorder involved.
• For a reader-friendly explanation of the genetics involved go to: http://sickle.bwh.harvard.edu/scd_inheritance.html Here you will notice that a person with a normal hemoglobin gene from one parent and a sickle cell gene from the other parent is said to have “a condition called sickle cell trait.” See another instance of this terminology at http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhatIs.html .
• It is misleading to call the situation of having one altered gene a trait or to say the person has a condition.
• “About 2 million Americans, or 1 in 12 African Americans carry the sickle cell trait,” or one sickle cell gene
• “sickle cell disease [two genes] occurs in about 1 in every 500 African-American births
• and 1 in every 1000 to 1400 Hispanic-American births.” (http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/sca.shtml  Emphasis added; note that by simply adding the word “carry,” the ORNL statement helps avoid misunderstanding.)

Thoughts about the Facts:

• Is it likely that this unusual terminology would be applied to persons with one sickle cell gene if they were primarily Caucasians, rather than Blacks?
• The only similar case is that of “thalassemia trait” (or “thalassemia minor”). Thalassemia is also a blood disorder which, like sickle cell anemia, mainly affects populations frequently stigmatized—in this case persons from the Mediterranean area.

o   In the 1920s, the restriction of immigration from Southern European nations such as Greece and Italy was spurred on by fears of pollution of the American gene pool.

o   In 1924 Harry Laughlin of the Eugenics Record Office presented testimony to the U.S. House of Representatives Committee on Immigration and Naturalization regarding the “intellectually and morally defective immigrants primarily from eastern and southern Europe,” illustrating his commentary with a photo of an Italian mother and daughter (Lombardo, P. (n.d.). Eugenic laws restricting immigration. http://www.eugenicsarchive.org/eugenics/list2.pl, p. 6).

My Hypothesis:

• I suspect that sickle cell and thalassemia are the only instances of labeling the carrier state with unique terminology.
• A search of PubMed at http://www.ncbi.nlm.nih.gov/pubmed for the term “trait” recommended “Also Try sickle cell trait and thalassemia trait” but no others.

So What?

• Discrimination on the basis of one’s genetic make-up is a realistic concern and can extend even to whether the carrier state is pathologized, labeled, and referred to as a health “condition.”
• Significantly, student athletes may sign a waiver releasing NCAA and their university from liability instead of being tested for sickle cell “trait.”
• The implications of this are discussed in an article that appeared in the September 9, 2010, issue of the New England Journal of Medicine, 363 (11). It examines the decision to screen student athletes for “sickle cell trait.” The lead author, Vence L. Bonham, J.D., is an Associate Investigator of the Social and Behavioral Research Branch of the National Human Genome Research Institute.
• As the NEJM article points out

o   the waiver alternative hints that reducing legal liability is NCAA’s main goal.

o   the testing program is essentially an experiment for which it is impossible to grant voluntary consent because students need athletic scholarships which depend on maximal performance and cooperation.

o   the entire testing initiative would be rendered unnecessary were the eminently reasonable recommendations for sickle cell anemia carriers during conditioning sessions extended to all athletes.

• These simple precautions can be found at  http://web1.ncaa.org/web_files/health_safety/SickleCellTraitforCoaches.pdf
  
• A not-so-simple, detailed explanation of various studies and findings by John Kark, MD, is at http://sickle.bwh.harvard.edu/sickle_trait.html