“Negative.” “Normal.” “Fails to confirm the diagnosis of . . .” “Etiology of the patient’s disease phenotype remains unknown.”
These are words I heard repeatedly in the first 11 years of my son’s life. Even as new genes for my son’s rare muscle disorder were discovered around the world, negative or “normal” genetic test results were reported back to us 13 times. …
Peter White, PhD, Assistant Professor of Pediatrics and Director of the Biomedical Genomics Core at Nationwide Children’s Hospital, led the winning team in CLARITY Undiagnosed, an international challenge that interpreted genomic data from five families with undiagnosed conditions. The team also took part in CLARITY’s first challenge in 2012, receiving special mention. Here, White describes the team’s approach to these “toughest of the tough” patients.
The CLARITY Undiagnosed challenge was markedly harder than the first CLARITY challenge. This time around, we were given whole-genome sequence datasets for five families and asked to produce clinically useful results through improved interpretation and reporting. It turned out to be a fantastic learning experience for all of us, and we will be using the collaborative approach we developed to solve genomics challenges in our own patients. …
Most adult transplant centers require patients to walk a set distance in under six minutes to remain a good candidate for lung transplant. The thought is that if patients cannot meet this minimal threshold, then their chances of being able to rehabilitate after transplant are diminished. In pediatrics, this is also important. But Dawn Freiberger, RN, MSN, Boston Children’s Hospital’s Lung Transplant coordinator, says there are other factors that have to be considered.
“The walk test is just one piece of the pie,” says Freiberger.
Some 5 to 17 percent of all children have developmental dyslexia, or unexplained reading difficulty. When a parent has dyslexia, the odds jump to 50 percent. Typically, though, dyslexia isn’t diagnosed until the end of second grade or as late as third grade — when interventions are less effective and self-esteem has already suffered.
“It’s a diagnosis that requires failure,” says Nadine Gaab, PhD, an investigator in Boston Children’s Hospital’s Laboratories of Cognitive Neuroscience.
But a new study led by Gaab and lab members Nicolas Langer, PhD, and Barbara Peysakhovich finds that the writing is on the wall as early as infancy — if only there were a way to read it and intervene before the academic, social and emotional damage is done. …
Disease-causing mutations can be incredibly subtle: Sometimes a single-letter change in a gene or a so-called somatic mutation (affecting only some of the body’s cells) can be enough. Researchers report this week in Neuron that both kinds of mutations — easily missed on standard blood and saliva testing — play a role in autism spectrum disorder (ASD).
Scientists have suspected a role for these mutations in brain disorders, but the technology to find them has only recently come online. Sampling brain tissue is the most likely way to find them, but brain biopsies aren’t something you do every day.
The war on pediatric cancer hasn’t been going so well in the past couple of decades, says Timothy Triche, MD, PhD, a cancer researcher at Children’s Hospital Los Angeles. The existing intensive chemotherapy regimens carry a lot of “unfortunate baggage” for children in terms of lifelong morbidity, and haven’t brought about a tremendous change in outcomes, he says.
“We really don’t have a lot of new drugs, if any, and we really don’t have new targets,” he said at Boston Children’s Hospital’s Global Pediatric Innovation Summit + Awards last month. “Underlying this is the fundamental problem that we don’t understand a lot more about childhood cancer than we did before.”
In a Discovery Roundup highlighting four big ideas in pediatric care, Triche made the case for targeting the genome’s “dark matter” — the vast number of RNAs made from the genome that do not code for proteins. …
Dizziness is fairly common in children, but it can be very hard to diagnose the cause. Any number of conditions can produce dizziness, and children are a special challenge since they often can’t describe what they’re feeling.
“One of the toughest things to figure out is, is it a problem with the vestibular system, or is it part of something else, a heart problem or an eye problem?” says Jacob Brodsky, MD, director of the Balance and Vestibular Program at Boston Children’s Hospital. “Then, the next challenging part is determining whether it is an inner ear problem or a central vestibular disorder — a problem with the brain.”
A definitive answer often requires a battery of tests that few providers outside Boston Children’s can perform in children, as they require sophisticated and expensive equipment. But with an ordinary bucket, an iPhone, an $18 app and some Velcro, Brodsky can quickly get a good indication of whether a child has a vestibular problem—and specifically an inner ear problem. …
Two new developments offer glimmers of hope to patients with rare, hard-to-diagnose conditions—validation of the power of crowd sourcing and the prospect of bringing cognitive computing to rare disease diagnosis. Both developments were announced at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards (#PedInno15).
The crowd-sourcing challenge, CLARITY Undiagnosed, yesterday announced the findings of 21 teams that competed from seven countries. The winning team, Nationwide Children’s Hospital (Columbus, OH), was awarded $25,000. Invitae Corporation (San Francisco) and Wuxi NextCODE Genomics (Cambridge, MA) were named runners-up.
Each team received DNA sequences and clinical data from five families whose illnesses had eluded many prior diagnostic attempts—in some cases, even prior genomic sequencing.