She stares at me, owl-eyed, empty. There is no embarrassment when time ticks on. She stares. A sound breaks her gaze and her eyes lock on to a new target. She is nowhere to be found. The old her, that is. The woman who showed such immense joy and love as a mother is gone. Her husband moves her around the streets of their city like he is pulling a 100-pound weight on wheels in his hand. She goes with the flow. He and the children have built a life around this new woman – this wife and mother who is lost to a genetic disease that has stolen everything human about her. She is only 38 years old. She no longer speaks. She stares. She is led to the bathroom, to the shower, to the table where they put a fork or spoon in her hand for her to eat.
She spoke her last word three seasons ago. And now no one knows whether she understands much of what is said around her. Her husband could say that the sky is falling and she would not budge. She clasps her hands, wrings them every which way, and is locked in her own world. The culprit that has destroyed so much of her brain is a gene called MAPT. The gene makes a protein called tau, which is needed to maintain the structure of the cell. Tau is accumulating abnormally in her brain. You can see it on the brain scans. Her frontal and temporal lobes are abnormally small and significant chunks of brain tissue are missing. There have been more than 44 different MAPT mutations linked to hereditary forms of frontotemporal dementia, also known as FTD.
This young woman has FTD. Her symptoms began in 2014. She was withdrawn. She was still speaking, still raising her children, working and playing golf. By 2015, she was asking co-workers to proof her writing. She stopped working in the summer of that year. Her language comprehension seemed to tank that fall. By October, this classy young woman who had always been mindful of healthy foods was ordering hamburgers and fries at fast food restaurants – even when the kids were not around. She began speaking in two-word sentences.
Doctors in her home state thought she had depression. Things got worse and there was talk in the family that maybe she had the same disease that killed her mother. She was diagnosed with FTD at 48 and died five years later. She had some of the bizarre behavior and language problems that her daughter was now having. She was diagnosed with FTD in 2015. Last year, she was referred to the Memory and Aging Center. FTD is a specialty here.
Neuropsychological testing showed lots of problems, but she was still able to discriminate between two objects and recognize famous faces. She could draw a complex picture and remember most of the pieces to draw it from memory a few minutes later. She followed most instructions during two days of testing.
This year, there would be none of that. She stared. Her husband was the one to answer every question. She stared and rubbed her hands. His words tumbled around her – the man achingly lost his wife and their children lost a mother. She showed no sense of knowing what anyone is talking about.
He must do everything for her now. If he hears the shower running he can find her under the spray in her clothes.
She’s lost her manners. She stuffs her mouth with pancakes. During the MRI scan she put a red earplug in her mouth and started chewing. She wears diapers now.
She acts nothing like her former self, the husband said. “I take her everywhere but she is nowhere,” he says. “The woman I fell in love with is just gone. This disease has taken her away.”
Genetics is magical and complex – and many times unfair. Many individuals enrolled in research at the MAC meet with a genetic counselor who will make those cool modular trees with boxes and circles and colors indicating whether relatives are sick, and if so, what is wrong. The goal is to figure out if there is a genetic component that drives the disease.
We are growing old in a time in history when genetic research is exploding. Back in the day, in the 1990s, genetic counselors specialized in either prenatal or pediatric genetics. Prenatal screening had kicked in two decades earlier to attempt to identify inborn errors of metabolism like phenylketonuria. Scientists had discovered that a strict diet could prevent a buildup of the amino acid phenylalanine and prevent intellectual disability. Then, there was widespread screening for carriers of sickle cell disease in African Americans and Tay-Sachs in Jewish populations. Quickly, such testing was widely recommended and genetic counselors were on hand to deliver the news and sometimes help families make extraordinarily difficult decisions.
Families with genetic illnesses have made it possible to identify risk genes and gene mutations. In 2002, I wrote about a woman who’d just turned 30 and had testing for a rare mutation that causes early-onset Alzheimer’s disease. Her 38-year old sister had lost her memory to AD and the family opted for testing. It turned out that this younger sister carried the same APP gene mutation. She will develop the same disease as her sister. She and her husband decided to use genetic testing for pre-implantation genetic diagnosis (PGD). Their doctors selected only those embryos that did not contain the APP mutation. They went on to have three healthy children. They understood that she would probably develop dementia while they were very young and that the disease would lead to severe disability and death.
The last decade has seen the identification of many genes that can cause different types of FTD. In addition to the MAPT gene on chromosome 17, there is another gene on the same stretch of DNA that makes progranulin protein. Mutations in the GRN gene also cause FTD. There are other genetic mutations too.
Last year, this young mother who was losing so much of herself had blood drawn during her workup at the MAC. They sent the sample off for genetic testing. Two months later, Joanne Taylor, a genetic counselor at the MAC, would call the husband and explain that the lab identified a mutation on the MAPT gene and that the MAC team believed it was the cause of her ravenous dementia.
This year, it took greater effort to pack up his wife and undergo another two days of testing. She has progressed a lot in one year. Still, he understands the importance of research, especially in this case where each of his children has a 50 percent chance of having inherited this genetic mutation. “You are damned if you do and damned if you don’t,” he says. “I am hoping that one day your work will lead to a cure,” he tells the team, which includes neurologists, neuropsychologists, a nurse, social worker, genetic counselor, and research coordinator.
The husband has reached out to Joanne Taylor many times since she delivered the news about the MAPT gene mutation. “This disease scares me to death,” he says.
Joanne Taylor arrived at the MAC fifteen months ago after spending the first two decades of her career counseling pregnant women at Lucile Packard Children’s Hospital Stanford. She’d grown up on the Stanford campus. Her father was an administrator and most of her childhood friends had a parent who worked at the university. She fell in love with the idea of genetic counseling when she was pregnant with her first kid. A friend in her prenatal exercise class was a genetic counselor. Years later, she signed on to one of the few programs in California. She took the two-year master’s degree at Berkeley.
She was ready for a change when she heard about an opening at the MAC. This young couple was one of the first cases she had. “I love the idea of research. You think about puzzles and problems,” she says. The MAC genetics program sends out DNA samples to a lab that sequences at least eight genes linked to the neurodegenerative diseases they see. The MAPT mutation that was identified in this young woman has only been reported in one other family. Apparently, having more than one family makes the mutation real for FTD.
Taylor sent a letter to the young woman’s family. She has several siblings. Some have traveled to California for testing. None of them wants to know whether they have the mutation that would cause FTD. This research is important because understanding the pre-symptomatic life of a patient will help unravel the how and when of the disease.
There are vexing decisions that come across Taylor’s desk. About six months ago a man arrived at her door with a puzzle. He’d just found out that his mother had been diagnosed with FTD. She was now gone but he was wondering whether he had the same gene mutation that had caused her FTD. He is in his 40s and has four children. This is a personal choice. Taylor, as always, was hoping that the test would be negative, for everyone’s sake. It was not. Since then, they speak on occasion. “I can still hear your voice telling me that I have the gene,” he tells her.
Personally, this genetic counselor would not want to know that she had a genetic mutation that can cause a disease that has no treatment. The goal of all the work at the MAC is to understand these diseases enough to help develop ways to treat them.
For now, that is what this other father with three children and a silent wife hopes. He is one of about 300 families enrolled in two NIH-funded studies called ARTFL and LEFFTDS that are underway at more than a dozen medical centers in North America. The studies are gathering data on families with rich genetic histories of FTD. While there are no answers for his wife, they will come back next year. He and Taylor have developed a strong bond. He knows that he can call her anytime. The life of a genetic counselor doesn’t end with the delivery of test results. That is just the beginning.
Jamie Talan is an Atlantic Fellow at the Global Brain Health Institute, a collaboration between UCSF and Trinity College in Dublin. She will be spending several months at UCSF writing about the inner workings of the brain and giving voice to patients and the doctors, nurses, psychologists, geneticists and researchers involved in building the foundation for a whole body of non-Alzheimer dementias that are often missed, lost or ignored.