Research

Rapid exome sequencing (rES), a blood test that can quickly detect genetic abnormalities, is helping obtain timely genetic diagnoses for critically ill children at Seattle Children’s.

A newborn boy was admitted to Seattle Children’s Neonatal Intensive Care Unit (NICU) earlier this year with arthrogryposis — a condition where an infant cannot move, their joints becoming frozen in place. When geneticist Dr. Jimmy Bennett met the infant, he was on a respirator and could only move his eyes.

“We didn’t know the cause of the arthrogryposis and could not tell the parents much about their son’s prognosis — whether he would ever come off the ventilator or if he would be intellectually disabled,” Bennett said. “With so little information, it was difficult to decide how to proceed.”

This family had a previous pregnancy that was similarly affected. Bennett believed the cause might be genetic and recommended rapid exome sequencing (rES) — a blood test that can quickly detect genetic abnormalities.

Less than a week later, the test identified a specific condition that led providers to administer an appropriate therapy. Before long, the child was moving.

“Never in a million years would we have tried this therapy without the genetic test results,” Bennett said. “Two weeks later, the patient was off the ventilator and moving all four limbs. It was like a miracle.” Read full post »

Dr. Doug Diekema, director of education in Seattle Children’s Treuman Katz Center for Pediatric Bioethics.

Providers often must negotiate with patients and families, but how should disagreements be addressed when the discrepancy is rooted in the patient’s culture or beliefs?

The Journal of the American Medical Association published an example of such a dilemma in 2008.

“Ms. R” was a 19-year-old woman who lived in the United States for several years while her parents lived abroad. She underwent an elective cranial surgery related to complications of a genetic syndrome.

The neurosurgical procedure was successful, and Ms. R seemed to be doing well until 10 days later when she complained of an acute, severe headache and quickly became unresponsive.

Ms. R had suffered an intracranial hemorrhage. Following repeated apnea tests, she was declared brain dead.

Because Ms. R’s parents had not been able to say goodbye, she was kept on a ventilator, pending their arrival.

Her father, who held Ms. R’s durable power of attorney for health care, arrived within 24 hours of the declaration of death. He requested the ventilator be continued and asked the provider to administer a traditional Chinese medicinal substance to Ms. R.

The father explained the substance is often used in his native country for a range of conditions, including coma. He asked the treating team to combine “the best of Western and Eastern medicine” to benefit his daughter.

Providers were unsure how to proceed. Should they comply with the family’s request, even though they felt certain it would not benefit the patient’s physical condition?

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Representing about 70% of cleft lip and palate cases worldwide, non-syndromic cleft lip and palate typically occurs in isolation without other physical abnormalities. Credit: Getty Images.

A study conducted by an international research team, which included investigators from Seattle Children’s Research Institute, implicates variants in four genes as a primary cause of non-syndromic cleft lip and palate in humans. The genes, associated for the first time with cleft lip and palate, encode proteins that work together in a network, providing important insight into the biological basis of one of the most common physical malformations. Read full post »

Picturing her daughter making it to her first birthday was difficult for Rachael Rowe as she watched her baby struggle to survive each passing day waiting for a liver transplant.

Time officially took its toll on Feb. 6, 2018 — four months after 10-month-old Raylee was put on the transplant waiting list.

“I remember it was 3:00 a.m. in the morning when I heard Raylee screaming in pain,” said Rowe. “Never in my life had I heard a baby cry like that before. It was terrifying.”

After spending three hours trying to comfort her normally smiley and happy baby, Rowe took Raylee to the emergency room near their home in Portland, Oregon.

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Brendan Bittinger, 9, was diagnosed with autism spectrum disorder using a team evaluation model developed at the Seattle Children’s Autism Center.

Some say ‘it takes a village to raise a child.’ At Seattle Children’s Autism Center, this concept came to life to a certain degree through the development of a collaborative method for diagnosing autism in children that aimed to improve the diagnostic process and increase efficiency, with the potential of leading to better patient outcomes.

Linda Bittinger’s 9-year-old son Brendan found his ‘village’ at the Autism Center in June 2017 when a team made up of providers from different disciplines came together for a thoughtful diagnostic evaluation that would shape his treatment path to progress.

“When we received his diagnosis, I felt a sense of optimism,” said Bittinger. “I had less worries knowing there were opportunities for treatment. And since then, he’s made tremendous strides.”

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New research could pave the way for a rapid screening test capable of diagnosing submicroscopic malaria infections.

While the global health community has made great strides toward eradicating malaria through prevention and treatment strategies, rapid and inexpensive methods to diagnose submicroscopic malaria in individuals who have no clinical symptoms and undetectable levels of disease-causing parasites in their blood remain an unmet need.

With the unexpected discovery of a panel of peptides from several proteins encoded by the parasite that causes malaria, new research underway at Seattle Children’s Research Institute could pave the way for a rapid screening test capable of diagnosing submicroscopic infections.

Such a diagnostic test could permit the widespread screening of all individuals in high-risk regions – a practice global health experts agree is likely required to eradicate malaria. It could also provide a way to diagnose submicroscopic malaria infections during pregnancy, which bring substantial health risks for the pregnant woman, her fetus, and the newborn child. Read full post »

Dr. Lakshmi Rajagopal’s lab at Seattle Children’s Center for Global and Infectious Disease Research is studying how group B strep establishes an invasive in utero infection during pregnancy.

Group B strep (group B streptococcus or GBS) is a common bacteria present in the vagina of about 1 in 4 women. In the U.S. and other developed countries, pregnant women are tested for GBS with those who test positive given antibiotics to help protect babies from infection. In low resource settings where GBS testing and treatment is often not accessible, invasive GBS infection leads to a large percentage of still births and an estimated 3.5 million preterm births each year.

Despite the substantial impact on pregnancy outcomes, scientists know little about how GBS establishes an in utero infection. In a paper published in the Journal of Clinical Investigation, Dr. Lakshmi Rajagopal, a principal investigator in Seattle Children’s Research Institute’s Center for Global Infectious Disease Research describes a newly uncovered mechanism by which GBS gains access to a woman’s uterus. Read full post »

Aaron (left) poses with Dr. Mike Jensen, director of the Ben Towne Center for Childhood Cancer Research, at the Strong Against Cancer CELLebration fundraising event.

Seattle Children’s doctors and researchers are leading efforts to better treat cancer in children, adolescents and young adults by boosting the immune system with T-cell immunotherapy. Patients who cannot be cured with standard therapies are benefiting from clinical trials developed at the Ben Towne Center for Childhood Cancer Research, and supported by Strong Against Cancer.

One of these patients is Aaron. When he feared he might be out of treatment options, Aaron found hope at Seattle Children’s. Now, he shares his story.

Cancer is such an ugly word. On the internet, it has become normal for people to use it to describe things, ideas or people they don’t like. But for me, that word only brings back painful memories of fighting a disease I would not wish on my worst enemies.

I was first diagnosed with acute lymphoblastic leukemia in January 2013. I was 19 years old, living in Vancouver, Canada, and studying computer science at Simon Fraser University.

I became suddenly ill while on a cruise vacation with my family. I had a fever that wouldn’t go away; nausea for no reason; and extreme fatigue. I needed to sleep all the time. I could barely walk. Climbing a flight of stairs felt like trying to climb Mount Everest.

We knew something was very wrong, so my family took me to the Emergency Department at Vancouver General Hospital.

I still remember lying on the hospital bed after the doctor delivered the bad news — I had leukemia. I couldn’t believe it. I asked the nurse as he was putting in my IV, “How long do you think it’ll take before I get better?”

He replied, “My friend, I’m afraid this is just the beginning of a long and difficult journey for you.”

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New research from Seattle Children’s offers fresh insight into how the brain sets the pace of breathing.

Next time a workout has you winded, the inhibitory neurons in your brain may be to blame. This is according to new research from Seattle Children’s Research Institute that offers fresh insight into how the brain sets the pace of breathing.

In a study published in the journal Nature Communications, researchers used laser light to manipulate very specific classes of neurons responsible for breathing. The technique, known as optogenetics, helps scientists isolate neurons in the brain to study their function.

When stimulated in the lab, the researchers found excitatory neurons – the brain’s go signal – actually slow breathing, while inhibitory neurons – the brain’s stop signal – intervene to make breathing more rapid. In addition to explaining how the brain adapts breathing in response to everyday cues, the finding could lead to more precise treatments for neurological conditions that frequently involve breathing abnormalities. Read full post »

Dr. Jim Hendricks, president of Seattle Children’s Research Institute.

Ranked as one of the top pediatric research centers in the U.S., Seattle Children’s Research Institute has accomplished so much in its 11-year history, and there is much to look forward to in 2018. Here, Dr. Jim Hendricks, president of Seattle Children’s Research Institute shares with On the Pulse what’s in store for the year ahead.  

1. Cancer immunotherapy

Seattle Children’s continued immunotherapy work is going to be very exciting this year.

In 2017, Seattle Children’s opened three new clinical trials offering innovative chimeric antigen receptor (CAR) T-cell immunotherapies for children and young adults with relapsed or refractory acute lymphoblastic leukemia. Currently, there are four Pediatric Leukemia Adoptive Therapy clinical trials underway at Seattle Children’s (PLAT-02, PLAT-03, PLAT-04 and PLAT-05), with others expected to open this year. Read full post »