Bertrand Might’s medical problems were apparent from infancy. Born to Cristina and Matt Might in 2007, Bertrand seemed to be constantly moving, as if unable to rest, and could not be consoled. Each potential diagnosis, such as brain damage, was ruled out through testing.
The answer to Bertrand’s medical mysteries came when he was four years old. A revolutionary approach to medicine, exome sequencing, offered the piece to the puzzle that explained his developmental disabilities, which included life-threatening seizures and the inability to walk or speak.
By sequencing the exome, the less than two percent of the genome that codes proteins and gives rise to the vast majority of known genetic disorders, Cristina and Matt learned they each carry a mutation in the NGLY1 gene. The chance that Bertrand would inherit each mutation was about one
in four million.
But Bertrand did inherit this mutation, so he was not producing an enzyme that helps to recycle cellular waste by removing sugar molecules from damaged proteins.
The Mights shared Bertrand’s story widely in the media and online. By doing so, they met other patients who had inherited the NGLY1 mutation, and had also struggled to find a medical answer. Since finding the cause to their son’s medical problems, the Mights helped reshape genomic medicine toward encouraging the sharing of information among specialists and patients when a diagnosis remains elusive.
Today, sharing information on rare or undiagnosed genetic conditions is the guiding mission of the Undiagnosed Diseases Network, a consortium of clinical and research centers tasked with solving the most challenging medical mysteries.
The UDN is where Lauren Briere ’02 and Elizabeth Krieg ’12, both genetic counselors in the Boston area, provide clarity and guidance to the patients who have otherwise exhausted their search for answers to their medical conditions.
“There is a surprising number of people who clearly have something, often something serious, and have seen every specialist, and still don’t have an answer,” said Briere, a genetic counselor at Massachusetts General Hospital and the clinical coordinator for the UDN.
Patients who apply to the UDN are often the most desperate. They have eluded medical diagnoses that explain the causes of their symptoms, while struggling to live and adapt with disabilities. What’s worse, they are often the only ones known to be suffering from their particular conditions. UDN can serve as a starting off point so that patients can find others suffering from the same illness, and share treatment options or even the frustrations of non-options.
“There are a lot of challenges to living with the severe medical problems that come with a genetic disorder,” said Krieg, a genetic counselor at Brigham and Women’s Hospital, and program manager for the Brigham Genomic Medicine and UDN site coordinator. “But it can be harder to not know anyone who is also going through that same thing, or [has the] same diagnosis as you.”
As genetic counselors, Briere and Krieg each serve as the point person between patients, their families and their medical teams. Genetic counselors handle the delicate work of answering questions, coordinating testing and explaining results.
“The basic tenets of genetic counseling are to give information, conduct risk assessment and help patients to make an informed choice that is their own,”
“A big part of my job is education,” Krieg added. “I interpret and explain what is going on. And together we set some neutral goals. If they are not sure why we want to do certain tests, it’s a matter of explaining it in terms that they might understand, or would resonate with them.”
While still a student at Connecticut College, Briere was interested in medical professions but knew she didn’t want to become a doctor.
“I wanted more time with patients, and to work with people more than doctors do,” she explained, and and thus took as many science courses as she could while she figured out a possible career path.
“When I took biology, one of my favorite and most interesting parts was always the small genetic unit in the end,” Briere said. In one particular class with Jean C. Tempel ’65 Professor of Biology Stephen Loomis, a passing mention of genetic counseling caught her attention.
“I remember going back to my basement dorm in Blackstone House, looking it up, and found it was the perfect combination of what I wanted.”
Yet the field of genetic counseling was still emerging, and few options existed as she searched for a career internship.
“No one had heard of it,” Briere said. “The profession had been around for 20 years at that point, but it was small. Most hospitals had one genetic counselor, and not a lot of turnover.”
As Briere was preparing to graduate in 2002, the field of genomic medicine was on the verge of taking off. The Human Genome Project brought together international researchers tasked with identifying the genes that make up DNA, essentially creating a blueprint for the human body.
With the mapping of the human genome, the genetics field exploded. Genetic testing and genome sequencing were now possible for the greater population, becoming more affordable and accessible with each year. Briere earned a master’s degree in genetic counseling, and has been working in the field since 2006.
Krieg also realized the field of genetic counseling met her goals of entering a medical profession, so Krieg self-designed a genetics major at Connecticut College.
“It seemed like a good balance of patient interaction and clinical care, and had opportunities in research and working clinically,” said Krieg, who earned her master’s in genetic counseling in 2014.
Krieg describes her role with the UDN as being the point person for the client, and for the families.
“Every case that we accept is completely different,” Krieg said. “It involves being familiar with patients’ medical records. Discussing the different conditions we might be thinking about. And knowing what strategy we might use with genetic sequencing.”
Exome sequencing, like the kind used to find Bertrand Mights’ underlying genetic condition, is not often covered by medical insurance. But research centers like the UDN cover the cost of such procedures for its participants. The UDN is funded by the National Institutes of Health Common Fund.
Collaborative efforts like the UDN will continue to be at the core of genomic medicine in the future.
“We can share a candidate’s genetic variants, and general information about symptoms,” Briere said. “We share in a group of online databases, and link to other clinicians, who can share that information. If two people document the same change in a gene, we get an email saying we have these cases that have matched. It’s a way to find other cases and hopefully generate research.”
Krieg added, “Many of the different research projects out there are having success solving cases and finding answers for things that haven’t been diagnosed,” which obvioulsy offers hope to those suffering from undiagnoased diseases.