DISEASES, DISORDERS & CONDITIONS
TABLE OF CONTENTS
1. bipolar disorder / 2. breast-cancer gene / 3. pedophilia / 4. ambiguous genitalia /
5. kleptomania / 6. transgender / 7. Cancer / 8. Multiple sclerosis
Scroll down to a numbered question and click on it to find its answer.
1. What is the cause of bipolar disorder? – Answer: Bipolar disorder (BD), or manic-depressive illness, is a mental disorder that affects mood: the person suffers wide swings from one pole to the other – from manic episodes lasting a week or more that are characterized by excessive energy and enthusiasm, grandiosity, lack of focus and judgment, and engagement in high-risk activities such as frequent sex with strangers or wild spending sprees; to the other extreme characterized by severe depression, sleep disturbance, inability to make decisions, loss of interest in life activities, and frequent suicidal thoughts and suicide attempts, which are sometimes carried to completion (if untreated, BD leads to suicide about 20% of the time). Symptoms typically first appear in the late teens or early twenties, with men and women being affected similarly. The condition afflicts 1-2% of the population. There is no cure, but the disorder can often be managed with a combination of medication and psychotherapy. (Some especially creative people have had this disorder; see Touched with Fire: Manic-Depressive Illness and the Artistic Temperament, by Kay Redfield Jamison.)
Bipolar disorder has multiple causes. They have not been fully identified, nor are the connections between the causes and the effects fully understood. Part of the problem is that what is called “bipolar disorder” cannot be diagnosed precisely; the symptoms vary greatly. This variability might reflect different degrees of severity of the same condition, or it might represent somewhat different disorders with different causes.
One’s risk for developing bipolar disorder is increased if other family members suffer from it, and increased greatly if one has an identical twin with BD. Therefore genes must be involved. But sometimes when one identical twin develops BD, the other twin does not. Therefore there must be other, non-genetic factors that can precipitate the condition – perhaps stress of some kind, or some depression-inducing circumstance in childhood that acts as a trigger to shift the brain into a pattern of bipolar episodes.
On the genetic side of the picture, more than two dozen different genes have been implicated. Many are naturally variable genes, which individually have only minor effects on basic brain cell functions or the body’s response to stress, effects entirely within the normal range. But certain unlucky combinations of them can make one especially susceptible to developing bipolar disorder if the external circumstances are right for it – just as a building, upright under normal conditions but structurally weak, can become particularly unstable after a flood or an earthquake.
2. How does the BRCA gene cause breast cancer? Answer – So far three different genes have been given the name “BRCA”; they are BRCA1, BRCA2, and BRCA3. Of the three, the BRCA1 gene is the one most frequently involved in breast cancer. (Sometimes “BRCA” is used as a general designation for any of these genes; sometimes “BRCA” is used informally to mean just BRCA1.)
The normal BRCA1 gene is an important gene, one of many responsible for regulating normal cell division. It is the abnormal BRCA1 gene (altered, damaged, or lost) that can cause problems.
Here is what happens:
To regulate cell division, all active cells in the body have both an accelerating system and a braking system, used by the cells in a manner analogous to the way a driver might control the speed of a car by using both the brake and the accelerator at the same time, pressing down on one and letting up on the other as required. One part of the normal cell-division braking system is the BRCA1 protein, information for which is carried in the BRCA1 gene. If by chance both normal copies (inherited from the two parents) of the BRCA1 gene in a breast cell are lost or changed by mutation, then no active BRCA1 protein can be made, and the cell loses its braking-control on cell division. It may then give rise to a lump of abnormal cancer cells that continue dividing in an uncontrolled fashion. In a majority of cases, the susceptibility to breast cancer is not inherited, because usually the mutation or loss of the BRCA1 gene happens just in a breast cell, not in an egg cell or sperm cell.
(Most cases of breast cancer do not involve the BRCA1 gene at all, but are the result of mutations in other parts of the division-accelerating or division-braking system.)
In inherited breast cancer (about 5% of all breast-cancer patients with BRCA1 involvement), an abnormal copy of the BRCA1 gene has already been inherited from one of the two parents. This means one copy is already damaged or missing, right from conception, leaving every cell in the body with only one good copy of the gene. The chances are high that sooner or later, in one breast cell or another, this remaining good copy will also be lost or damaged, leaving the cell without the proper cell-division braking capacity. Many women in this situation are likely to develop breast cancer, and at an earlier age than typical for women in general. These women carry a mutated BRCA1 gene in all their cells, including their eggs, and therefore may pass this bad gene on to their children. In these cases (a small percentage of all cases), breast cancer may run in the family.
(Incidentally, a man whose mother had an inherited form of breast cancer may have had the defective BRCA1 gene passed on to him. He is unlikely to develop breast cancer himself, but he can pass the defective gene on to his daughters.) 19.xii.15
3. Is pedophilia caused by genes? – – This question is better phrased this way: Are there inherited genetic differences between people with pedophilia and other people? Answer: While particular forms of genes might be a minor cause of pedophilic tendencies, non-genetic events influencing brain development in fetal or very early childhood are probably more important.
Pedophilia (from the Greek for “child” + “love”) is an adult’s sexual attraction to, and sexual fantasies about, a pre-pubertal child. It has been estimated that about one man in thirty has sexual fantasies about children. The frequency of women with such fantasies is lower.
A recent (2013) study from Finland found that among adult male twins, both twins experienced sexual fantasies about children slightly more often when they were identical twins (who share all their genes) than when they were fraternal twins (who share on average only half their genes). Therefore there is some slight influence of genes on at least some adults’ having sexual fantasies about children. The main cause for pedophilia is not known, but is probably not genetic. It may involve alterations in brain connections occurring during brain development in the fetus.
A distinction should be made between pedophilia and child molestation. Just as we all have fantasies of various kinds that we don’t act on, the majority of pedophiles with sexual fantasies about children do not act on them. Child molesters, by contrast, typically come from dysfunctional families, have suffered early brain injuries or other early trauma, have lower-than-average IQs, low self-esteem, poor socialization skills, and may themselves have been sexually abused as children. Often they may not even have sexual attractions to their underage victims.
If the primary symptoms of pedophilia – persistent, repeated, uncontrollable and distressing sexual fantasies about children – interfere with normal day-to-day living, the condition is classed as a mental disorder. It can often be successfully managed by means of medication and psychotherapy.
Useful discussions of pedophilia can be found in Margo Kaplan’s New York Times Op-Ed piece, “Pedophilia: A Disorder, Not a Crime” (Oct. 6, 2014), and the Virtuous Pedophiles website (http://www.virped.org/).
11.i.16 (Thanks to Aurolyn Luykx for pointing out errors in a previous answer to this question.)
4. Babies with ambiguous genitalia – When a newborn baby is found to have “ambiguous genitalia” (the external genitals don’t look quite right for either a baby boy or a baby girl), are there tests that would help the physician and the parents decide what can be done, and whether to raise the baby as a boy or as a girl? – Answer: Yes, there are tests that can be done, and the results can sometimes be helpful in deciding on a course of treatment that might provide a satisfying life later on. But even when the cause for the newborn’s ambiguous genitalia is found, it is often not clear what the best treatment is, nor what its long-term outcome might be for the treatment decided on.
In normal development, a gene in the Y chromosome in a fertilized egg sets off the development of the fetus toward maleness. In the absence of a Y chromosome, the fetus develops as a female. The full development of the male or female reproductive system, however, including the external genitalia as well as gender identity and sexual orientation, is a long and complicated process, and is not fully understood. The normal pathways of sexual development can be disrupted by the occasional chromosomal abnormality, the existence of a rare mutation in any one of dozens of important genes, and abnormal hormone levels during fetal life. Other causative genetic and non-genetic factors remain unidentified.
Abnormalities affecting the reproductive system, appearing in less than one percent of all births, are commonly called “disorders of sex development” (DSD). Many people with DSD don’t discover their condition until the normal changes at puberty fail to occur; it is then found that the testes or ovaries or other internal parts of the reproductive tracts haven’t developed normally. In most of these cases there is no real “ambiguity” about the external genitalia. But in about 10% of all cases of DSD (about one newborn in every few thousand births), the external genitalia are truly ambiguous: a clitoris approximating a small penis in size, or a very small penis and little sign of normal testes, or other abnormalities.
A number of tests are available to help determine the cause:
(1) General physical exam: are height, weight, and other physical traits within normal ranges? Are there other genetic or metabolic conditions that might have influenced the condition?
(2) Medical history of family and relatives: is there any indication of disease, medical disorders or infertility in the extended family?
(3) Looking at the chromosomes: is the baby XX, or XY? Are there other chromosome abnormalities?
(4) DNA tests: are there any mutations in genes known to be involved in normal sex development?
(5) Internal visualization (magnetic resonance imaging or MRI, CT-scan, or ultrasound): are ovaries or testes, uterus or prostate gland, other internal parts of the reproductive tract, visible?
(6) Hormone tests: are levels of testosterone and other hormones within normal ranges?
Treatments may involve hormone supplements, surgery, and psychological counseling later on. A professional team of pediatricians, geneticists, endocrinologists, urologists, and surgeons offers the best chance for providing the best future quality of life for DSD patients.
In some cases the child is best advised to be raised according to the sex chromosomes; in other cases according to the external anatomy; in still other cases, according to the internal anatomy, hormone levels, and how well the child responds to hormone supplementation. In order to provide the best chances for a good quality of life for the child and the later adolescent and adult, early diagnosis is important, because changes occurring later, at puberty, may be difficult to reverse. Unfortunately, even with the best medical advice, patients later in life will sometimes experience difficulties with sexual and love relationships and other social adjustments. Psychological counseling and the assistance of support groups can be helpful.
In one recent case, a teenager from a poor family without early access to quality medical care had been raised as a girl, but at puberty she experienced marked changes in the male direction. A chromosome test indicated normal (male) XY chromosomes. Physical examination revealed a small penis, undescended testes, seminal vesicles, prostate gland, and no uterus or vagina. Gender reassignment procedures might have been advised, but the teenager identified as a female and wanted to remain a female. She wanted especially not to suffer the social stigma that comes with changing gender. So female hormone treatments were begun, and surgery gave her a partial vagina, according to her wishes. In this case, social factors were more important than purely medical test results.
One of the difficulties in this area is insufficient information on outcomes of particular decisions made around the time of birth and early infancy. The long-term consequences are not known until fifteen or twenty years later. Nevertheless, relevant surveys are gradually accumulating. Genetic diagnoses often do help the parents (with the aid of physicians) decide whether to raise the infant as a boy or as a girl. Such decision are not infallible, but they do give a better-than-average chance for the child’s reasonably satisfactory social and sexual life when he/she grows up, particularly when psychological counseling and support-group participation is available.
Some of the information given here came from these articles:
G. B. De Paula et al., 2016. “408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing.” International Journal of Endocrinology 2016:4963574. PMID: 28018429
P. A. Lee et al. & Global DSD Update Consortium, 2016. “Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care.” Hormone Research in Paediatrics 2016; 85(3):158-180. PMID: 26820577
C. Costa et al., 2014. “The dilemma of the gender assignment in a Portuguese adolescent with disorder of sex development due to 17β-hydroxysteroid-dehydrogenase type 3 enzyme deficiency.” Endocrinology, Diabetes and Metabolism Case Reports. 2014:140064. PMID: 25298885
5. What do we know about the cause of kleptomania? – Answer: Not much. Kleptomania is a recurring or periodic compulsion to steal, without any real desire for the object stolen. Kleptomania seems to be associated with changes in brain chemistry, because treatment with drugs that affect brain chemistry is at least partly effective in some cases. Rather than being an isolated behavioral disorder in itself, kleptomania may just be a symptom of some underlying psychiatric condition, such as depression, anxiety, obsessive-compulsive disorder, an eating disorder such as bulimia, or addiction (e.g., to alcohol, drugs, or gambling). It is likely that in many cases genes are somehow involved, because genes are often involved in some way in every other known psychiatric disorder. But there are no definitive genetic studies on kleptomania per se, so it is not known which genes might predispose a person to compulsive stealing.
If genes sometimes appear to play a role in predisposing a person to kleptomania, that doesn’t necessarily mean genes “cause” kleptomania. For example, certain forms of some genes might set the stage for some problem behavior, and if it includes kleptomania, a spurious correlation between genes and kleptomania would be found. But the kleptomania itself might be the consequence of a certain kind of upbringing; in that case, psychological factors, not genetic ones, might be key. One doesn’t have to “geneticize” absolutely everything about human behavior.
6. What causes the transgender condition? – Answer: The transgender condition (also known as “gender identity disorder” or “gender dysphoria” (meaning “hard to bear one’s gender”) is a condition in which a person feels that their gender does not correspond to their anatomical sex. It’s a biological condition, a developmental disorder in which the brain’s perception of “the gendered self” doesn’t line up with anatomy.
Transgender people have been estimated to make up about one-half of 1% of the population. The estimate is based partly on questionnaires, so the actual numbers may be somewhat higher, because not everyone would answer truthfully. Transgender women (feeling female, although anatomically male) are more common than transgender men (feeling male, although anatomically female).
Genes are thought to play some role in gender dysphoria, for two reasons. First, the condition occurs within a given family somewhat more often than would be expected by chance (such as a family with two cousins both of whom are transgender). Secondly, when one twin of an identical twin pair is transgender, the other twin is somewhat more likely to be transgender too. It is not known which particular genes might be involved.
Sometimes when one member of an identical twin pair (sharing exactly the same set of genes) is transgender, the other is not. Therefore genes can’t be the only thing causing gender dysphoria. There must be other factors that are also important—perhaps particular circumstances in the womb during fetal development, or maybe variations in hormone levels affecting brain development.
The transgender condition, when it occurs, is variable from one person to another. It is sometimes described as ranging from “mild” to “strong.” This is not surprising. In the embryo and fetus the early development of sexual anatomy and the later development of the brain are not closely coordinated. The later connection between brain and anatomy could be affected differently by hormones, genes, and variable conditions in the womb. Some people describe feeling that that their mental “gender identity” didn’t match their bodies from the earliest age they can remember. Other people don’t feel the mismatch until later in childhood, or in adolescence, or even in adulthood. There are also a few who experience gender dysphoria in childhood, but then as they grow older come to feel that their bodies and their sense of gender begin to correspond with each other after all. For these reasons, some doctors and health-care workers prefer to wait until a person’s puberty or later before recommending hormone treatments and corrective surgery. Others feel that better long-term adjustment can sometimes be achieved with treatment before puberty, because then the individuals are able to avoid the secondary sex traits they don’t want (such as menstruation, patterns of fat distribution, breast development, facial hair, and voice changes).
In the absence of positive support from family, counselors, and society at large, gender-based harassment and depression are common in transgender people, and rates of suicide are high, especially among adolescents and young adults.
Here are two important background references:
Zucker, Kenneth J., 2017. Epidemiology of gender dysphoria and transgender identity. Sexual Health. October; 14(5):404-411. PMID: 28838353
Richard A. Friedman, “How Changeable Is Gender?” New York Times, Aug. 22, 2015.
Thanks to Diana Luykx and Jim Gross for comments.
7. Will cancer ever be cured? Are cancers different enough that some could be cured but not others? – Answer: This is like asking, “Will viral disease ever be cured?” There are so many different kinds of cancer, just as there are so many different kinds of viral disease, that a “cure” for one kind may not always work for another kind.
A cancer originates as a result of a change (a mutation) in a cell-division-control gene in a cell. The cell no longer controls the rate at which it divides, or whether or not it will divide at all. Uncontrolled cell division is what all cancers have in common. The original mutation may be caused by a rare accident in the chemistry of DNA; it may be induced by harmful radiation or chemicals; it may be caused by certain kinds of virus; or it may be inherited from a parent.
Almost any cell in the body might experience a cancer-initiating mutation. Each kind of cell may be using a slightly different set of genes to control its division, and there are several hundred kinds of cell, and dozens of division-control genes. A mutation of any control gene could be the beginning of uncontrolled division (cancer) of that cell type. Given all the possible cell types and all the possible gene mutations, there are potentially thousands of different kinds of cancer, each slightly different from the others: where it’s located, what kind of cell it originated from, how fast it grows, and whether it’s malignant or not.
Because mutations will always be happening, a cancer of one kind or another will always be arising. Cancer will never be “cured” in the sense of being eliminated totally from human populations. But the frequency of mutations in general by can be lessened (by stopping smoking, or reducing UV-exposure). And new methods are continually being devised and refined to treat cancers of various kinds when they occur, so that the incidence of cancer in general can be reduced, as well as, in increasing numbers of individual cases, eliminated.
8. What causes multiple sclerosis (MS)? – Answer: The word sclerosis comes from a Greek word meaning “hard”; it often refers to a place in the body where hardened connective tissue has replaced softer tissue as a result of injury as, for example, with scarring. The word is also sometimes used to refer to any local damage to a body tissue. The local damage in multiple sclerosis (MS) is in multiple places in the brain, leading to a failure of muscle function, weakness or paralysis, uncontrolled muscle contractions, lack of coordination, sensations of burning or numbness in the skin, incontinence, and other symptoms. In some patients the symptoms are relatively mild or intermittent, with near-normal function at some times and more severe symptoms at other times (remitting/relapsing MS). In other patients the symptoms get progressively worse as time goes on (progressive MS). The onset of the disease occurs around age 30 on average, but can be anywhere between 20 and 50. The worldwide prevalence of MS is about 1 person in every 3000, with women about twice as susceptible as men, for unknown reasons. Except for severe cases, life expectancy is about normal. Some famous people who were diagnosed with MS are Teri Garr, Joan Didion, Richard Pryor, Neil Cavuto, Montel Williams, and Alice Sara Ott.
MS is an autoimmune disease. With autoimmune diseases, one’s immune system begins attacking one’s own cells and proteins as if they were foreign invaders. This might happen if a real foreign protein (brought into the body by a virus, for example) is similar enough to one of one’s own proteins that the immune system begins attacking them both. Or it might occur if some of one’s own natural proteins suffer a (non-genetic) chemical change so that they now look foreign to the immune system. In the case of MS, the inappropriate targets of the immune system are proteins in the myelin sheaths that cover the nerve fibers in the brain, which are necessary for normal transmission of nerve impulses.
Given that the immune system is very complicated and sensitive; think of the painful inflammations that sometimes follow an injury or infection, or all the allergies that human beings experience. Therefore it’s not surprising that no single factor is responsible for all the cases of MS. Many different factors might activate the immune system inappropriately. The frequency of MS is influenced by certain naturally occurring gene variants involved with immune-system functions. Your chances of developing MS are somewhat higher than average if you have a relative with MS, because you and your relative share some of the same genes. (According to some studies in Sweden, if you have a parent or sibling with MS, your chances of developing MS yourself might increase from about 1 in 3000 to about 7 in 3000—a significantly higher risk, but still not a high risk). In instances where a patient with MS has an identical twin, the other twin also develops MS about 30% of the time; that’s more often than would be expected by chance, so shared genes contribute to the likelihood of getting MS. But 70% of the time the other twin does not get MS—so genes must not completely determine whether or not MS develops; other factors are also important. According to wide-ranging surveys, diet, obesity, vitamin-D deficiency, smoking, air pollutants, and viral infections (but not vaccinations against viruses) contribute to increasing the likelihood of MS. The disease is sometimes described as being “triggered by environmental factors in genetically susceptible people.” This is another way of saying that both genes and environmental factors are involved.
There is no cure for MS. Treatments that sometimes are partially effective in slowing the progression of MS include anti-inflammatory drugs, drugs that inhibit the activity of immune-system cells, and drugs that promote myelin repair. Corticosteroid injection or blood-plasma replacement may relieve some symptoms in the short term. Management of MS is sometimes possible, but there is no one-size-fits-all treatment that is effective in every case, because of the variability in the causes and the symptoms from person to person.