Do Fathers Matter?: What Science Is Telling Us About the Parent We've Overlooked (6 page)

In one of his early publications, Surani called these maternally or paternally marked genes “imprinted genes,” as if they were stamped with an identifier saying they came from mother or father. The name stuck. Further research showed that most human genes are
not
imprinted. Only about 100 of the estimated 20,000 human genes have so far been found to carry these special chemical imprints, although some researchers believe there are more.

But what function do they serve? Surani examined all the mouse fetuses that failed to survive gestation. He saw that when he conducted the experiment with two sets of mothers’ genes, the embryos developed reasonably well, but not the placentas. With paternal genes, the opposite was true: the placentas looked normal, but the embryos didn’t develop properly. This was the first hint concerning what imprinted genes do. It didn’t tell Surani much, but it did tell him that paternal genes and maternal genes were doing different things. Something about the imprinted genes of fathers was important for the development of the placenta, and the imprinted genes of mothers were important for the development of the embryo.

Evidence for imprinted genes continued to accumulate, and Surani and Solter eventually convinced their colleagues that the findings were legitimate. The existence of imprinted genes in humans was confirmed as well. Mendel wasn’t wrong, exactly; his findings were merely incomplete. Even though only a small number of human genes are imprinted, that’s enough to explain why parthenogenesis didn’t work. Offspring need one set of paternally imprinted genes and one set of maternally imprinted genes to survive.

Once geneticists recognized that imprinting was essential for reproduction, they realized that it can also make us vulnerable to a variety of severe genetic disorders. In the case of genes that aren’t imprinted, we have an insurance policy. We get one copy from each parent, and the two are interchangeable. If one fails, the other often keeps working, and so we stay healthy. There’s a good reason that evolution endowed us with backup copies of most genes. Mutations are fairly common, and so illness and malfunctions would be much more common if we were not able to switch to an undamaged backup that can function like an emergency power supply in a blackout. It usually doesn’t matter which version of a gene works, as long as one of them does. But with imprinted genes, one copy is stamped “off.” That’s why imprinting has such a huge cost. If a mutation occurs in the single working copy, we’re in trouble. You might expect that such mutations would be devastating, and that is precisely what scientists have found.

*   *   *

I found Surani’s groundbreaking work fascinating. Here was a critically important way in which fathers contributed to their children’s well-being that was important to scientists and also to families who have children with these illnesses. I’ve written about genetics and inherited diseases often enough to know that we all walk a very thin line between health and disease. A single stutter or typo in the genetic code can mean the difference between a healthy child and one who is very sick or who does not survive. With the discovery of imprinting, it now seemed that line was even thinner and more perilous. I decided I should talk to children with some of these illnesses, and their parents, to show that what might seem like an abstract finding in genetics can have serious consequences for fathers and their children.

My first visit was with the family of Alexander Baker on Manhattan’s Upper West Side. Alexander, a bright, cheery, and exceedingly friendly child, was about to turn five. When I walked in, he was deeply involved in a game on his iPad but pleased to have a visitor in the house. He looked up and greeted me with a broad smile before turning back to his iPad, but kept stealing glances at me while I talked to his parents. Alexander’s mother, Maria, thirty-five, is a writer, and his father, Thomas, also thirty-five, is an HR director. Their second child, James, nearly a year old, rested quietly in Maria’s arms.

When I opened my laptop to take notes on our conversation, Alexander immediately ran behind me to look over my shoulder and see what I was doing. When I showed him, he smiled, nodded, and watched for a while before returning to his iPad. (Sociability is a characteristic of children with Angelman syndrome.) After I’d been there about twenty minutes, he handed the tablet to Maria and pointed at something on the screen. She looked at him and said, “Say ‘Help me.’” He hesitated and then said it. The phrase is one of only a few that he can manage to say. He learned them through extensive drills with a speech therapist. In addition to being unable to speak, Alexander is developmentally delayed, has frequent seizures, and will require care for the rest of his life.

Thomas and Maria suspected something was going on with Alexander in the first few months of his life. By the time he was eight months old, when he was diagnosed with multiple developmental delays, they were certain. “We were very aware of signs of trouble,” Thomas told me. “People around us would say that we were new parents and we worried too much—and that boys were slower to develop.” But they knew that wasn’t it. They began making the rounds with various specialists, eventually seeing more than twenty of them—geneticists, developmental pediatricians, and neurologists. “These were possibly the hardest and most painful years in our lives so far—knowing that there was something wrong and going into appointment after appointment, and coming out with no answers or another misdiagnosis.”

Diagnoses of autism and cerebral palsy were suggested but soon rejected. Doctors then concluded that he had what they call pervasive developmental delay (PDD), which sounds official but is merely a blanket diagnosis that means he was failing to meet the usual infant and child milestones for development. Because they had no idea what caused it, they labeled it PDD “not otherwise specified,” or PDD-NOS.

The Bakers shared the news with their families and then got their first break. Thomas’s brother-in-law’s sister called. She had written a research paper on Angelman syndrome for a college biology class, and she immediately thought of Alexander. His lack of speech and the way he flapped his hands when he was excited sounded to her like it could be Angelman. Those can be signs of autism, too, so she couldn’t be sure, but it was another lead. Alexander’s parents went back to the experts, who quickly dismissed the concern. But they persisted. In November 2008, just before Thanksgiving, Alexander was tested, and the diagnosis of Angelman syndrome was confirmed. “It was a bittersweet moment,” Maria told me. It was a relief to find out what was wrong. But they now knew they were dealing with a very serious condition that couldn’t be easily corrected. “Before that,” Thomas said, “we hoped it was a phase he could outgrow.” The Bakers quickly learned that Angelman syndrome is a rare and severe disorder of the nervous system. There is no treatment for it, although parents of children with Angelman syndrome have identified a long list of therapies that they think and hope will ease the symptoms. Thomas and Maria told me that Alexander gets “every type of therapy you might imagine.” These include attending a special therapeutic school; occupational therapy to tune his fine-motor skills; a kind of physical therapy intended to improve balance and movement called the Feldenkrais Method; speech therapy; aquatherapy; and, every weekend, special therapy on horseback intended to move his hips in a way that will help him walk better. Some of this is covered by insurance, but a lot of it is not. Maria has put her career on hold while she works full-time as a caretaker for Alexander.

While it’s common for children with Angelman syndrome to have seizures, the form those seizures take can change. Not long ago, Alexander entered a period in which he seemed distant and unable to respond. The Bakers didn’t know what to make of it at first, but his doctors determined that he was having what are called nonconvulsive seizures. By the time he was diagnosed, he had gone through a month of almost continuous seizures; that’s what had led to the vacant look. Seizures are not only dangerous in themselves, but they lead to setbacks in Alexander’s other treatments.

In the absence of a cure, Alexander will need intensive care for a lifetime. He is a charming child, but there are developmental milestones that he will likely never achieve. He still wears a diaper at night and will probably never be able to dispense with it. And while the Bakers have a warm and loving relationship with Alexander, which he reciprocates, they know their lives together will be difficult, as Thomas explained. “We are never likely to have him tell us that he loves us—at least in those words. We will continue to need to guess at whether he had a good day or a bad day, or if something hurts. We worry about what our lives will look like when our adorable young boy becomes a teenager or young adult, and his drool and need to hug everyone he sees won’t be as cute or as welcome by others.” The Bakers have struggled to provide as much care for Alexander as they could afford. In the meantime, they wait and desperately hope for a cure, or anything that might improve Alexander’s outlook.

All of Alexander’s symptoms are due to a mutation in a cluster of imprinted genes on human chromosome number 15. These are maternally imprinted genes, meaning they are operational only when inherited from a mother—the technical term is that they are maternally expressed. The copy children inherit from their fathers is turned off in the brain. When the mother’s copy isn’t present or isn’t functioning because of some error or abnormality in the gene, the child has no working copy. The silent copy from the father can’t serve as a backup to remedy the lack of this critical gene.

But that’s not the end of the story. The cluster of genes on chromosome 15 that cause Angelman syndrome also contains a gene that is expressed only when it comes from the
father
. When this paternal gene is not expressed, children are born with a disorder called Prader-Willi syndrome. These children have developmental delays similar to those seen in Angelman syndrome. But one hallmark of Prader-Willi is its curious effect on eating. Children with the syndrome don’t nurse well and are generally underweight before weaning. After weaning, however, the children develop voracious appetites and almost inevitably become obese. They also show developmental and physical delays, including poor muscle tone, which can affect their movement. As with Angelman, there are a variety of therapies that can ease some symptoms, but there is no treatment that comes even close to a cure.

Prader-Willi represents a different example of the failure of imprinted genes. It is caused by a mutation in the same cluster of genes that cause Angelman syndrome, but in this case it’s a paternally imprinted gene that is afflicted with a mutation. After my visit with the Bakers, I got in touch with the family of a boy with Prader-Willi syndrome. We arranged for a visit, and one night shortly afterward I took the Long Island Rail Road from Manhattan to the home of Michael Stevens, thirty-eight, an accountant in New York City. His son, James, was five and in kindergarten. He and his wife, Barbara, thirty-seven, a nurse, were not unlike the Bakers. Both families had the means to provide extra help to their children, including therapies not covered by insurance. Barbara, like Maria, had stopped working outside the home to become James’s full-time caretaker.

Michael and Barbara were fortunate to get a proper diagnosis for James shortly after he was born. Signs of trouble had appeared late in the pregnancy, when doctors noted unusually low fetal movement. Their doctor decided to induce the birth early, in case there was a problem. When James was born, he didn’t cry. Barbara had developed gestational diabetes, and because that can cause the fetus to gain weight, James was sent to the intensive-care unit for observation. The specialist there suspected Prader-Willi syndrome. James’s testicles had not descended—a key indicator. And Barbara was zeroing in on that diagnosis, too; as a pediatric therapist, she had worked with children with Prader-Willi. “I didn’t even get to fire up the cigar, you know?” Michael said. Genetic tests confirmed the diagnosis two weeks later. James was in the hospital for six weeks.

Barbara was feeding James dinner when Michael and I arrived at their house. Because of the danger of overeating and obesity, Barbara feeds James and controls his diet rigorously. He eats four times a day—200 calories for breakfast, 300 for lunch, 200 at afternoon snack time, and 300 for dinner. Barbara also gives him human growth hormone, fish oil, coenzyme Q10 supplements, an amino acid supplement, carnitine, calcium, multivitamins, and a laxative, the last because of digestive problems associated with the disorder. He hasn’t yet developed the insatiable appetite, but they know the day is coming. “This is the fearsome, daunting characteristic of the syndrome that people dread,” Michael said. “You hear stories of teenagers who are 400 pounds.”

Although Prader-Willi children are not known for the sociability that is seen in Angelman syndrome, I found James to be just as charming as Alexander. Like Alexander, he seemed happy to have a visitor. When his mother and I went upstairs to see his bedroom, he ran up behind us, wanting to show it to me himself. He was especially proud of his electric guitar, which he was just learning to play. James’s intelligence is “at the low end of normal,” Barbara said.

When James was born, Barbara and Michael were ready to buy a new house, and they took James’s special needs into consideration. The house they built has a kitchen and pantry that can be completely sealed off from the rest of the house. The cabinets and doors are locked. “Kids are up in the middle of the night, grabbing food, stealing food, eating out of the trash—I can’t tell you how many stories we hear like that,” Barbara said. “If they know they can’t get at it, it’s better for them.” This is not just hearsay; extreme and insatiable appetite is a hallmark of Prader-Willi syndrome.

My visits with Alexander and James and their parents helped me understand the consequences of disorders in imprinted genes, and the seriousness of the boys’ illnesses underscored how important imprinting is. While mothers and fathers both make genetic contributions to their children, this was another area of research in which it was clear that the contributions of fathers extend far beyond what you might expect from the tiny package of DNA carried inside a single sperm.