Living legacy: is heredity destiny? (hereditary illnesses) Allison Adato; Andrew Eccles.

Abstract: Diseases that are hereditary in families can be detected early if family members are alerted to look for signs of the ailment. Cancer, sensitivity to certain drugs, sickle cell anemia and degenerative muscular diseases are some of the diseases carried throughout profiled families.

Full Text: COPYRIGHT Time Inc. 1995

The NIGHT CAROL Krause learned she had colon cancer, she paced her New York City apartment, unable to sleep. The exact same cancer had killed her grandfather at age 33. Both of her parents, plus five aunts and uncles, had lost battles with other cancers. Her youngest sister, Susan, had been diagnosed with ovarian and uterine cancer just weeks before. Now it was Carol's turn. But she was only 40, she kept thinking, and her son was barely four--old enough to understand disease and pain, too young to have to live without a mother. Then, at four a.m., the

noise of a car accident   14 stories below jolted Carol out of

her disturbing reverie. Today, five years later, she can still recall the scene--police and paramedics pulling lifeless bodies from the wreckage. "I remember thinking, 'Those people were fine ten minutes ago. I was diagnosed with cancer a few hours ago. Yet I have a chance, and they don't.'" Cancer, she decided, need not be a car wreck.

Carol Krause's chances of beating the disease were much better than average: She knew her genetic past, had made her medical family tree and was familiar with the cancers--ovarian, uterine, colon, pancreatic--that had poisoned its branches (see page 68). Had she not known about her grandfather's colon cancer, she wouldn't have insisted on early screening (the American Cancer Society advises testing from age 50), she wouldn't have received an early diagnosis, and she might not have been successfully treated.

"A medical family tree," says Krause, "is about taking control." In this age of no-frills health care and insurance uncertainty, control is crucial; creating a medical family tree is preventive medicine everyone can practice. As Dr. Aubrey Milunsky, director of Boston University Medical School's Center for Human Genetics, says, "If you care about yourself and your children, you will do everything you can to know your family's medical history. It can save your life, and the lives of those who are dear to you." And it will become even more valuable as scientists continue to locate the genes that cause over 2,000 hereditary illnesses.

If you can find a pattern of illness, say for heart disease, you may find the motivation to exercise or to quit smoking. If you can identify a condition that can be treated prenatally, you may give birth to a healthy child instead of a sick one. If you can stay on top of illnesses for which you are at risk, you may save your life.

But delving into your family's medical past can exact an enormous emotional toll. It is devastating to learn that your chances of developing a disease like breast cancer are abnormally high. Should you contemplate a double mastectomy, on the theory that you might get sick later? And what if your tree reveals an illness like Alzheimer's? Should you not have children to spare them the pain of possibly having to take care of you later or of suffering the disease themselves?

SAVING A LIFE After you make a medical family tree (see page 69 for the technique), it's up to you to share it with your doctor, even if he doesn't ask. Remember, Carol Krause informed her doctor of her cancer risk, not the other way around.

Laurie Shrader, 25, of Beckley, W.Va., wishes she had known more about the paternal side of her son's medical family tree (see page 60). If she had realized that Justin, now four, was genetically disposed to retinal cancer, she believes he might not have lost his eye. As it is, the only reason Justin, who was then nine months old, didn't also lose his life is that his paternal grandmother, Barbara Glandon, recognized an odd spot in his eye as a symptom of the childhood eye disease that had plagued several generations of her family. Laurie had never discussed medical family history with Justin's father, from whom she is separated, but she won't make that mistake again: "If I ever have children with anyone else, I will know what diseases run in his family."

RISK MANAGEMENT Even if a disease is known to run in a family, when, where and if it will strike remains a maddening unknown. When Carol Krause's baby sister, Susan, was diagnosed at 38 with ovarian cancer, which had killed their mother nearly 20 years earlier, and also uterine cancer, Carol and her other sisters, Kathy and Peggy, had only one sure protection against the cancers that might or might not strike them: prophylactic hysterectomies.

Kathy, then 42, had not yet started a family. Carol hoped to have another child. Both decided to have the surgery. "I didn't feel I had any choice," Carol says. "With one child already, my primary responsibility was to him." Peggy, the oldest and the mother of four, was reluctant. Carol remembers how the sisters pleaded with her: "We said, 'You have to do this for us.'" Peggy gave in.

Genetic testing can prove what a medical family tree can only suggest. "Carrier testing is now possible for a large number of conditions, but you wouldn't normally ask for it unless there is a family history of those things," explains Dr. Francis Collins, director of the Human Genome Project, which aims to map all of our 50,000 to 100,000 genes. "We are all walking around with genes that don't work, and increasingly we're going to have the ability to find out about them."

But having the gene for a disease in your lineage does not necessarily mean that you will get the disease. In general, if a gene is dominant, only one parent need carry it for a child to be at risk for getting the disease. But if the gene for a disease is recessive, the child is at risk only if both parents pass it on. Take, for example, the case of Tami and Jerry Hubbard of Indianapolis (left). Like one in 12 black Americans, both Tami and Jerry are carriers of the gene for sickle-cell anemia. Understanding the odds--they had a one in four chance of having a baby with sickle-cell--they examined their medical family tree: It was full of carriers, but no one had ever had the disease. The couple's first child is a carrier, but healthy; their second suffers the excruciating pain caused by sickle-shaped blood cells sticking in her arteries. Her life expectancy may be as much as 20 years less than her sister's.

"Even her breathing hurts," Tami says, describing Avery's sickle-cell episodes, which occur every few months. "If it gets severe enough, the doctors give her morphine. We have some guilt that we passed this to her knowingly--if we had known somebody with the disease, if we'd seen how it affected them, we might have made a different decision." But then she thinks of how Avery is when she's pain-free and happy: "We can't imagine not having her."

In May, Georgetown University will release the results of a survey of people who have undergone genetic testing for conditions in their family trees. Of those polled, 83 percent said genetic testing should be used to learn if a fetus will be born with a disease. But we, as individuals if not as a society, must then decide what to do with that information. The Hubbards could have determined prenatally that their daughter would be born with sickle-cell. "I would have used that information to learn as much as I could before Avery was born," Tami says, "but I wouldn't have aborted." Other families make different decisions.

Sarah Peterson (not her real name), 31, made up her mind at a young age that she would never give birth to a child with Duchenne muscular dystrophy (DMD), a degenerative muscle disease that is carried by females but strikes only males: She had watched her brother suffer from DMD for 21 years before he died of it. "My husband and I decided that because the test is done early [at about 10 weeks], we would terminate the pregnancy if it was a boy with the disease," she says. Their families never knew about the first three pregnancies, each of which produced a male with DMD, or about the three abortions--which is why the couple has asked for anonymity here. They tried again. "It was a relief to finally tell people I was pregnant," Sarah says. Their son is now two, and Sarah is pregnant with a girl--who carries the DMD gene. "When she grows up, we will go over her genetic makeup and what it means," says husband John.

CAN WE KNOW TOO MUCH? "Gene discovery leads almost immediately to diagnostic abilities," the Genome Project's Collins explains. But what happens when we know a lot and can do too little?

"A doctor shouldn't automatically, in a knee-jerk way, say, 'If you're worried about having this disease, there's a test,'" says Nancy Wexler, a neuropsychologist at Columbia University. Counseling a patient about coping with a potential risk often has more value than confirming the risk, especially if a sickness is absolute and fatal, as it is with Huntington's, the horrible disease that killed Wexler's mother. Geneticist Milunsky agrees: "A doctor owes it to a patient to be sure they fully understand what effect an adverse result will have on them, on their mate, on their children. With Huntington's they're facing a progressive dementia, a loss of all their faculties. We know that the frequency of suicide in such families is much higher than the norm."

Nancy Wexler and her sister, Alice, a historian, were born with a one in two chance of having the gene for Huntington's, a gene that Nancy's research helped locate. Nancy, who is passionate about the privacy issues surrounding genetics, will not reveal whether she has had the test she helped devise. Alice discusses her choice not to be tested: "I can learn to live with the uncertainty of not knowing, better than I could live with a positive result." Alice knows that the risk of getting Huntington's decreases with age--she is now 52--but, she says, "the fear never totally goes away."

Some people choose not to be tested because they can't live with the thought that even if they test negative, their siblings might not be as fortunate. Cheryl Webb, 39, and Barbara Hatfield, 38, of New Brunswick, Canada, come from a close-knit brood of eight siblings, each of whom has a 50 percent chance of developing Alzheimer's, which struck their mother at age 51, and which has been traced in their family back to the early 1800s. "There are at least five chromosomal abnormalities that end in Alzheimer's," explains Linda Nee, who heads a National Institutes of Health study of this family. There is no test for hereditary Alzheimer's (only 1 percent of all cases) for the general population. However, last year Nee offered the family a test specific to their gene pool, followed by counseling. No one took her up on the offer. Says Cheryl: "It would be every bit as devastating for me to be 'clean' and for my sisters or brothers to have the gene."

Knowing of a risk, however, can be enough to force decisions. "After Mum died," says Cheryl, "I had this urge--I had to have a baby. I was thinking, 'They'll have a cure.' Or if I had him by the time I'm 30, and Mum took sick in her 50s, he would be at least 20 years old, not a young child needing a mother." Her son, Matt, is nine.

Barbara chose not to have children. "I just couldn't imagine my child going through what we went through with Mum," she says. But both sisters have grown beyond the long shadow cast by their family tree. As Cheryl explains, "We can't curl up and be depressed. This is memory-making time."

FAMILY SECRETS A Jewish superstition holds that even mentioning a disease in the home is tantamount to inviting the Angel of Death in for a glass of tea. Closeting family illnesses can guarantee their place in future generations, but tracking your family's medical history can be more than difficult when relatives don't want to deal with past or future unpleasantness. As medical ethicist Arthur Caplan, of the University of Pennsylvania, says, "You're intruding into people's privacy. Somebody may not want you to know there's no risk for a particular genetic disease because a child was adopted or born out of wedlock."

Nancy Schiller, 56, of Boca Raton, Fla., remembers her mother as distant, "talking to herself and having fits out of nowhere." In 1982 she was told that her own daughter, Lori, then 23, had schizophrenia. "I looked at Lori and I saw the same expression I had seen on my mother's face," Nancy says, explaining her reason for looking into her family's medical history. "I have a relative who's been in and out of institutions," she says. "When I say to his mother, 'Look, I really need this family history,' she says he's never been diagnosed." Lori has been successfully treated with medication, and Nancy has made peace with her past. "I had horrendous feelings toward my mother," she says. "When I realized [she had been sick], it was too late. I would give anything for the chance to say, 'I understand now. Nobody ever told me.'"

WHO HAS THE RIGHT TO KNOW? The stakes are too high not to go after the information you need, but what you dig up may be used against you. Because insurance companies have claimed that a risk identified in a family medical history is a preexisting condition, Paul Billings, a medical geneticist at Stanford University, strongly advises: "Pay for tests out-of-pocket if you want to control the information." Infuriating but true. He also suggests you ask your doctor to be discreet about what he writes on your medical chart.

"The medical record system is porous," says Nancy Wexler, citing as an example a situation where a doctor wrote "Father has Huntington's" on a patient's medical folder. "The insurance company canceled the daughter, who was perfectly fine." Billings tells of a woman who was having regular screenings for colon cancer, which ran in her family. Her insurance company excluded from her policy all care related to her colon--even though her aggressive approach to detecting the cancer probably put her at lower risk than most people. In the Georgetown poll of people who had had genetic testing, 51 percent had been denied either partial or full health insurance coverage.

"There is a risk that if you find out about a condition, it's going to be used against you in terms of your job or insurability," says Arthur Caplan. "Whereas if you didn't know, you could honestly say, 'I didn't know.' But, on the whole, I think it's better to have the information than not."

Ancient mapmakers marked rough waters, "Here there be serpents," as a warning by which to navigate. In exploring our medical family trees we become the cartographers of our ancestry, mapping the very stuff from which we are made. We can use what we find to protect ourselves, our children, our children's children. Carol Krause's legacy doesn't include only cancer but also the genetic information that can keep her son healthy. And it is this knowledge that can save our lives.

THE CANCER THAT STALKS HIS FAMILY APPEARS IN A LITTLE BOY'S EYE

In each generation of Barbara Glandon's extended West Virginia family, at least one child had died or had had an eye removed because something "wrong" was growing in it. Then, in 1991, while playing with her infant grandson, Justin, Barbara noticed a spot in his eye. His mother, Laurie Shrader, had seen it too, and had already taken him to the pediatrician, who was unalarmed. But Barbara remembered that same glassy stare in a niece who later lost her eye. She urged Laurie to take Justin to a specialist immediately. It was too late to save the eye--a tumor had already detached his retina--but not too late to save Justin, who would have died had the cancer spread to his brain. Since then, other relatives have had the retinoblastoma gene test, which was developed in 1989, and have been educated about the risk to babies. "As they come into the world," says Barbara, "you have to check 'em out."

A COUSIN'S DEATH REVEALS A RARE--AND FATAL--DISORDER

In 1978, Richard Davison was an athletic 37-year-old. A slip on an icy driveway landed him in the hospital for minor surgery on a broken foot. The day after the operation he was dead. The cause: malignant hyperthermia, a fatal allergylike reaction to certain anesthetics. The condition is hereditary and preventable--if the anesthesiologist is aware of the patient's susceptibility, he can use alternative drugs. Richard's death inspired his parents, Owen and Jean Davison, to search their family tree for others with the MH trait. They mailed 300 letters to relatives, telling them of their son's death and warning of the hereditary risk. The gene, it turned out, came from Jean's side of the family. When her niece Suellen Gallamore informed the hospital where she was to have fertility surgery about the MH in her bloodline, she says doctors refused to treat her. She recalls their dismissive response: "You have two healthy children. Be happy with that." Suellen would later squirm through a root canal without any painkiller because her dentist didn't know if local anesthetics would trigger MH. (They don't.) In 1981 she cofounded the Malignant Hyperthermia Association to educate medical providers about MH, so that people at risk, like her sons, would not suffer as she had. Or lose their lives, as her cousin Richard had.

A COUPLE CHANCES THE GENETIC ODDS

Jerry Hubbard, 32, learned he carried the gene for sickle-cell anemia during a physical for a college football tryout. Tami, 33, was also tested in college. Daughter Sara is healthy, but Avery has sickle-cell. The couple won't gamble again. Says Tami, "If we have any more kids, we're going to adopt." If the Hubbards do adopt, and the child's birth parents are known, they can ask the adoption agency to provide the child's family medical history. Adult adoptees can try to learn their own genetic past, even if their adoption files are sealed, by petitioning a court to open the records.

WHAT THESE SISTERS LEARNED SAVED THEIR LIVES . . .

Their mother's death from ovarian cancer in 1972 made the Krause sisters wonder if the same thing would happen to them. They started to investigate their medical past, quizzing their father about his sister's death. (Stomach cancer, he thought, although they would discover that it was, in fact, ovarian.) In 1989, Susan, then 38, had a pain in her side. Despite her family's history (opposite), doctors felt she needn't worry about cancer--she was too young. Surgery to remove an ovarian cyst revealed otherwise: a tumor on her ovary and cancer of the uterus. In addition to their already frightening genetic legacy, Carol, Kathy and Peggy now had two immediate relatives--a sister and their late mother-with ovarian cancer, meaning each had a 50 percent chance of developing the disease. The links between uterine, ovarian and colon cancers (all ran in their family) persuaded the women to have colon screenings. Carol's detected a tumor, which was quickly treated. But the three sisters' only sure protection against ovarian and uterine cancer, said their doctors, was to remove the organs before cancer could move in. The sisters opted to have prophylactic hysterectomies. Carol's and Peggy's showed they were disease-free. Kathy's proved immediately lifesaving: She already had cancer.

. . . AND HOW RESEARCHING YOUR MEDICAL FAMILY TREE CAN SAVE YOURS

Creating a medical family tree will require that you play the parts of a genealogist, detective and psychologist, all rolled into one. Interview your relatives, dig up death certificates and, if necessary, examine medical records. (The latter can be tough, as privacy laws limit access.) Carol Krause wrote How Healthy Is Your Family Tree? to help others gather for their families the kind of lifesaving information she found about her own. Her advice: Be patient but persistent, and for as many generations of blood relatives as you can (living and dead), learn the following:

1. If the person is deceased, when did he or she die, where, at what age, and what was the cause of death?

Knowing the date and town where the person died will help you get the death certificate from the local vital records bureau. A death at an unusually young age, especially from a particular illness, can be a red flag in analyzing your risk. For instance, a heart attack at 45 is very different from one at 75.

2. How old was the person when the illness began?

A relative who died of cancer at age 65 may have been sick for a decade or more. Inherited cancers usually occur earlier than noninherited cancers. An early-onset illness could mean that you, and your children, are also at risk.

3. What illnesses, health conditions or surgeries did the person have, and when?

An aunt or grandparent who lived to the ripe old age of 80 may have, over the years, endured or been treated for a host of serious conditions, such as hearing loss, cancer, arthritis or diabetes. The same ailments might develop in you or possibly strike a member of your immediate family.

4. What was the diagnosis, exactly?

If you are told that a person had "heart disease," find out the specifics (was it atherosclerosis, hypertension?) and how it was treated (pills, diet, bypass surgery). If he or she had cancer, ask what type, its location and severity. And for any cancer, inquire about the person's first symptoms. The information may be your key to early detection.

5. Did the person smoke, drink excessively or abuse drugs?

If so, it could be lifestyle, not genes, that caused the disease. Ask how long the relative was a smoker or ex-smoker, drinker or ex-drinker. (The more years the person did not indulge, the less likely the illness was caused only by lifestyle factors.) But beware: Substance abuse itself can run in families.

6. Is there a history of mental illness?

Families are often loath to reveal that a relative was institutionalized or had behavioral problems, but some mental illnesses do run in families. Awareness of the past can lead to proper diagnosis and treatment in the present.

7. How many pregnancies did your female relatives have, and what were the outcomes?

This too can be a sensitive subject. (What a family member describes as a stillbirth or miscarriage may in fact have been an abortion.) Pregnancy difficulties can run in families, and a known family history might help a doctor or genetic counselor treat the problems. Also ask if any children were born with birth defects, or died soon after birth or at a very young age.

8. What did the person look like?

Physical characteristics can be significant. While people who are obese have a tendency toward high cholesterol, thin relatives with very high cholesterol may indicate that a genetic defect is at work (such as familial hypercholesterolemia). Similarly, if your relative was fit and exercised and still developed heart disease, heart problems could be genetic.

9. Where did the person live or work?

An occupational or environmental exposure--not genes--may be the cause of poor health or disease.

WHAT TO DO WITH WHAT YOU FIND

Whatever you find, stay calm. Genetics is a complex science, and a pattern of illness doesn't necessarily mean that you are at great risk. Keep in mind that you share most of your genes with your first-degree relatives (parents, siblings, children), fewer with your second-degree relatives (grandparents, aunts, uncles), fewer still with your third-degree relatives (first cousins, great-grandparents), and so on. Your doctor, a specialist or a genetic counselor can help you understand the significance of your medical family tree.

However, you should consult a doctor promptly if you have:

Two first-degree relatives with the same cancer (breast, uterine, ovarian and colon cancers should be considered "the same").

One first-degree relative under the age of 50 with an illness usually associated with older people, such as cancer or serious heart disease.

Adapted from the book HOW HEALTHY IS YOUR FAMILY TREE?, by Carol Krause. Published by Simon & Schuster. Copyright 1995 by Carol Krause.