October 29, 2018

Some of the brightest minds in neuroscience recently converged on the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital for its fourth biennial symposium and workshop, in partnership with Baylor College of Medicine.

The special two-day event brought together nearly 300 physicians, scientists, patients, patient advocacy groups, pharmaceutical industry experts and leaders from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke, and the National Institute for Mental Health, to address key issues in the field of neuropsychiatry, an intersectional branch of medicine that deals with mental illnesses caused by organic disorders of the nervous system.

Neuropsychiatric disorders are a leading cause of disability and take a tremendous toll on society. In the United States alone, one out of five adults lives with mental illness. The spectrum of mental illnesses is vast, ranging from the extremely rare to more well-known conditions such as depression, anxiety, schizophrenia, ADHD, addiction and sleep disorders. Symptoms and their severity can vary widely from patient to patient, which makes them difficult to physiologically measure. For these reasons, neuropsychiatric disorders are some of the least understood – and some of the most difficult to treat.

“These disorders are a major health issue all over the world, however, therapeutic interventions remain limited,” said NRI/Baylor investigator and child neurologist Dr. Hsiao-Tuan Chao. “There is a growing need to understand the organic factors behind mental illness to facilitate a better understanding of the brain, as well as to develop more effective treatment strategies.”

The symposium opened with a welcome address from Dr. Huda Zoghbi, director of the NRI, and this year’s co-organizer, Dr. Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. The pair stressed the importance of identifying new research paths in order to develop targeted therapies that could not only help treat neuropsychiatric symptoms, but could also help mitigate or eliminate side effects and toxicities that far too many patients experience.

Over the course of the first day, presentations from leading experts addressed hot topics in neuropsychiatry. These included a discussion on how genetic mutations contribute to neuropsychiatric disorders; the involvement of neuronal networks in neuropsychiatric phenotypes; the impact of immune cells on these disorders; and a look into how adaptive deep brain stimulation could potentially help specific conditions. Each session gave way to a 20-minute moderated panel discussion on the topic at hand. This feature of the symposium is unique in that it leads to immediate discussion and active participation among the many different types of stakeholders present.

Following a day of stellar research presentations, the investigators split into three working groups that focused on Molecular Bases of Disease and Human studies, Circuits and Neuromodulation, and Young Investigators. The groups discussed not only everything they had heard over the course of the day, but also their vision for the next 20 years in neuropsychiatry, including the obstacles that currently exist and what is needed to overcome them.

The next morning, key points that had emerged from these discussions were shared with the audience. The working groups identified increased access to resources and funding as a major need. But unanimously, all of the young investigators noted the critical importance of building interdisciplinary, multi-institutional collaborations, with a focus on team science and data sharing.

“Building bridges between various disciplines aids in the identification of important areas of neuropsychiatry that require further investigation and therapeutic development,” said Chao. “Neuropsychiatry itself is an interdisciplinary field, and unraveling the causes for these conditions will require continued interdisciplinary collaborations to accelerate the pace of discovery.”

The proceedings will be published as a white paper in Science Translational Medicine, a leading weekly online journal and one of the event sponsors.

October 23, 2018

The New England Journal of Medicine (NEJM), one of the nation’s most respected peer-reviewed medical journals, has released a new study highlighting the groundbreaking work being done by the Undiagnosed Diseases Network (UDN), an National Institutes of Health-funded research consortium that includes the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital, Baylor College of Medicine, Stanford University and other institutions.

Identifying the genes responsible for rare or unknown disorders using traditional approaches is time-consuming work and can take years, or sometimes even decades. And though genetic sequencing is now a routine part of the care people receive for these types of disorders, many patients are still left without a diagnosis. According to the NEJM study, the collaborative UDN model may already be changing that paradigm.

The study reports that the UDN defined 31 entirely new syndromes, and of 382 completed evaluations, 132 patients received diagnoses, a rate of 35 percent – all in just 20 months. The study also found that of the new diagnoses, 37 percent led to non-therapeutic changes in care, such as narrowing of diagnostic testing, and an amazing 21 percent led to changes in therapies for patients.

“This is a major accomplishment in genomic medicine and a giant step forward for these patients and their families,” said Dr. Huda Zoghbi, director of the NRI.

The UDN was established in 2014 with the mission of providing answers for the millions of patients and their families affected by mysterious and rare conditions, but who, after years of extensive testing, still hadn’t received a diagnosis.

The NRI and Baylor have been at the forefront of discovery in the UDN since its inception, jointly serving as one of seven original clinical sites, where doctors and health care providers, ranging from neurologists, immunologists, nephrologists, endocrinologists and geneticists, come together to help find the cause of participants’ symptoms. Baylor, one of the UDN’s two original sequencing cores, currently acts as the network’s sole DNA sequencing site. The NRI and Baylor were also selected to serve as the UDN’s first Model Organism Screening Center (MOSC), which was spearheaded by NRI investigators Drs. Hugo Bellen, Shinya Yamamoto and Michael Wangler.

“The UDN recognized that the resources we had in place and our high throughput made us the ideal candidate to serve as a MOSC site,” Bellen said. “Because of our success with model organisms and the appreciation physicians have for our work, there will likely be a proliferation of MOSC sites in the future.”

In-depth fruit fly studies at the MOSC have helped physicians and scientists identify genes responsible for rare and undiagnosed disorders, leading to the diagnosis of some of the UDN’s most difficult cases. This collaborative effort, which also includes the University of Oregon, has already directly influenced how clinicians care for patients – patients like Avery Reilly.

At only a few months old, Avery began showing signs of a neurologic condition. She could not sit until age 3 or crawl until age 5, and today she cannot walk or speak. An appointment with Texas Children’s neurologist Dr. Timothy Lotze revealed Avery had poor muscle tone, which was delaying milestones. That initial appointment led to years of doctor visits and countless tests, all of which failed to reveal the cause of Avery’s developmental and speech delays.

Then in 2014, the Reillys heard about the NRI’s involvement with the UDN and submitted Avery’s case. For the first time in years, the family had hope. Using exome sequencing, researchers discovered Avery had a new type of genetic mutation. Then a team at the MOSC, led by Wangler, studied the mutation in a fruit fly model to see how the genes were affected. At long last, the Reillys had a diagnosis. What’s more, the discovery of Avery’s mutation led to a change in her medications, which could help slow the progression of her disease.

“The fact that we are able to help the UDN accelerate science to find actionable changes in therapies is very exciting,” said Zoghbi. “Helping people, and working to solve severe medical problems through basic research, and through unfettered collaboration, is what our work is all about.”

The NEJM study is the first to provide a detailed description of the inner workings of the UDN. It presents an in-depth analysis of the referral and acceptance patterns, diagnoses, impact rates and follow-up scientific investigations of 1,519 cases that were referred to the UDN in the last two years.

As the study points out, the most unique feature, and perhaps the biggest contributor toward UDN’s success, is its model of multi-institutional collaborations. Teams of researchers and physicians from participating institutions all over the nation leverage their multidisciplinary expertise and resources to quickly find specific diagnoses for patients with extremely challenging clinical cases, with no additional cost to the patients.

In addition to the original clinical sites and sequencing cores, the UDN also included a coordinating center as part of its phase I deployment. In 2015, a web-based portal, the UDN Gateway, was launched for patients and families to participate in UDN. The network recently expanded its footprint from seven to 12 clinical sites and also added a central biorepository, a metabolomics core and a new MOSC site.

Though the UDN’s larger focus is currently gene discovery, it’s the work being done at the NRI and Baylor that will set up the network’s next evolution.

“Once a gene is discovered, it’s natural that the focus should shift to finding out what the genes do, what the molecular mechanisms are, if they’re linked to other diseases, or if they can be manipulated with drugs,” Bellen said. “That’s what we’re doing at the NRI and Baylor now, and that will be instrumental in the next phase for the UDN. When that time comes, we’ll be ahead of the curve.”

Learn more about the recent research breakthroughs and patient success stories from the UDN and MOSC.

About the New England Journal of Medicine
For over 200 years, the New England Journal of Medicine has rigorously vetted and compiled the latest medical research in support of physicians and their patients. From the first uses of anesthesia to the most recent cardiology and cancer treatments, the New England Journal of Medicine has helped generations of clinicians enhance their knowledge and improve patient care.

Today, with rigorously peer-reviewed research, topical reviews, interactive clinical content and cases, the New England Journal of Medicine is the trusted source for essential findings in medicine.

The Periwinkle Foundation and Texas Children’s Hospital have teamed up with H-E-B to offer limited-edition reusable shopping bags featuring original Making A Mark artwork created by children touched by cancer and blood disorders at Texas Children’s Cancer and Hematology Centers. Just in time for the holidays, the bags will be sold in various H-E-B locations in the Houston and McAllen area as an effort to help raise awareness about childhood cancer.

“We are proud to partner with H-E-B to create these unique grocery bags that spotlight two very special pieces of original artwork created by these young artists,” said Erin Locke, Community Programs Director at The Periwinkle Foundation. “Raising awareness about childhood cancer is so important, and we are very grateful that H-E-B has joined us in this initiative to help spread the word.”

The one-of-a-kind shopping bags highlight artwork from past Making A Mark artists, Bethany and Blanca. Lost in the Sunflowers by Bethany, 12, showcases a young boy in a cowboy hat admiring a vibrant sunflower in a sea of rich foliage while Untitled by Blanca, 15, depicts the different outlooks on life by showcasing the positive and negative through bright and dark colors.

“This project is meaningful to H-E-B Partners (employees) who have volunteered with The Periwinkle Foundation’s Arts in Medicine program at Texas Children’s Cancer and Hematology Centers,” said Lacey Dalcour-Salas, H-E-B Public Affairs. “We have showcased patient artwork through the Making A Mark exhibition at two of our store locations and look forward to sharing their inspiration with our customers while increasing awareness of childhood cancer with the creation of this reusable bag.”

Since 2001, The Periwinkle Arts In Medicine Program at Texas Children’s has brought unique opportunities for self-expression, empowerment and development of coping skills to patients and their families while enhancing the healing environment and treatment experience in a variety of settings including outpatient and inpatient care areas. Periwinkle’s Arts and Creative Writing Program culminates each year in Making A Mark®, a travelling exhibition of more than 350 pieces of art and creative writing by children and teens touched by cancer and other life-threatening illnesses.

These limited-edition bags will be available for sale at more than 30 H-E-B locations across Houston while supplies last.

October 15, 2018

Diagnosed with a rare cancer called Langerhans cell histiocytosis, Shauntelle Tynan traveled 5,000 miles from her home in Ireland for a cure.

Earlier this month, Shauntelle rang the end-of-treatment bell at Texas Children’s Cancer and Hematology Centers!

During her bell ringing ceremony, she surprised Dr. Kenneth McClain, director of the Histiocytosis Program, with a donation toward histiocytosis research. A very special and emotional moment surrounded by family and friends. Join us in congratulating, Shauntelle!

To learn more about her journey, read Shauntelle’s blog at Texas Children’s Blog.

October 8, 2018

A world-class, multidisciplinary team at Texas Children’s is making huge strides in the care of children with extremely complex tumors.

The Head and Neck Tumor Program, begun in February 2016 as collaboration with partner institutions within the Texas Medical Center, has performed more than 20 major ablation free-flap multidisciplinary cases – a staggering number, considering the rarity and complexity of the tumors, which can be malignant or benign and can affect any combination of the sinuses, skull, jaw, mouth, neck and face. The ability to handle that volume of complex cases, combined with tremendous outcomes in the first two years, puts Texas Children’s Head and Neck Tumor Program among the best such programs in the country.

“Our institutional expertise is in taking care of these kinds of critically ill children, and Texas Children’s does it better than anyone,” said Dr. Daniel Chelius, attending surgeon in the Division of Otolaryngology and co-head of the program. “We’ve built a collaborative, coordinated program on that foundation of expertise in many different areas to provide the best care possible for the sickest children, while also reviewing and analyzing the care from every angle to see what went well and what processes could improve.”

Treatment of children with head and neck tumors around the country has historically been ad hoc, due to the varying functional issues or oncologic needs present from patient to patient and the extreme rarity of the tumors in any given city. Compound these complex physiological issues with the fact that most children these tumors have been treated in adult hospitals and the result has been a largely disjointed approach to care.

Texas Children’s Head and Neck Tumor Program, spearheaded by Chelius and Dr. Edward Buchanan, chief of Plastic Surgery, has developed a coordinated process around a multidisciplinary team approach that builds crucial experience in the treatment of these rare tumors and provides consistent, personalized care for patients – like 15-year-old Kami Wooten.

Last year, Kami began to notice swelling in her gums. Just months later, a benign tumor had covered half her face and threatened her vision. The team at Texas Children’s developed a specialized care plan that included removing the mass and reconstructing a portion of her face including the roof of her mouth and her orbit (eye socket). Additional procedures will be necessary in the future, but Kami and her family are grateful for the care Texas Children’s gave them.

Learn the rest of Kami’s story here.

The collaborative program comprises more than 10 Texas Children’s specialties and subspecialties, including Otolaryngology, Plastic Surgery, Neurosurgery, Oncology, Interventional Radiology and Anesthesiology, as well as a dedicated operating room team – led by Audra Rushing and Kelly Exezidis – that has been instrumental in building robust perioperative protocols. The additions of pediatric head and neck surgeon Dr. Amy Dimachkieh and microvascular reconstructive surgeons Dr. W. Chris Pederson and Dr. Marco Maricevich have increased the program’s abilities and improved the quality of its recommendations.

“It takes a lot of thought and planning to remove these complex tumors completely, while sparing as many nerves and other important structures as possible, and then to reconstruct those structures to provide both a good functional and cosmetic outcome,” Chelius said. “We tell our patients that the process might not be fast because they need the right surgery the first time. That requires recommendations from a team of experts, not just one surgeon. And that means carefully coordinating to make sure everything is as perfect as possible.”

The care required to treat these tumors, particularly if the patient is also undergoing cancer treatment, can also take a massive emotional and psychological toll. The Head and Neck Tumor Program provides additional care support through the department of Clinical Psychology and Child Life Services.

The team also uses technology to enhance the patient experience, from diagnosis to recovery. The program uses 3-D modeling to reconstruct children’s anatomy to help predict the extent of resection and to develop the surgical plan. The team also developed a data-driven protocol for pediatric tracheostomy removal, in close collaboration with Speech and Language Pathology, which uses a pressure monitoring device to signal when the trach is loose enough in the airway to be removed without adverse effects.

As a result of this innovative approach to care, 100 percent of patients treated have left the hospital breathing, eating and swallowing on their own. And the average stay in the hospital: just 14 days.

The program has been steadily building a referral base, drawing patients from across the region and from as far away as Mexico and the Middle East. In the near term, the team will continue to solidify the program, publish data and findings, and work to increase Texas Children’s reputation as the leading referral center for these complex cases. Long-term goals include building a basic science research infrastructure around understanding the underlying causes of these tumors, as well as collaborating with Texas Children’s Cancer Center and other research partners.

“We know that families are coming to us shocked and scared,” Chelius said. “We want them to know that we’re building our experience, we’ve walked families through this before, and we’re going to get them through this with the absolute best care available.”

Learn more about Texas Children’s Head and Neck Tumor Program.

Come join over 300 walkers for the Torch Relay on Friday, October 19 at The Woodlands Waterway Marriott Hotel in The Woodlands. The relay consists of a 3-mile walk around The Woodlands Waterway, followed by an after party with food, a band, DJ, carnival games, face painting, and a balloon and caricature artist.

All proceeds benefit the Children’s Miracle Network program at Texas Children’s Hospital and help children like Grace Anto, who was diagnosed with coronal suture craniosynostosis.

Resilience in children means being able to adapt well to adversity, trauma or even significant sources of stress. Grace Anto, a patient at Texas Children’s, is just that – resilient.

“When Grace was born in August 2007, it was obvious that she had some facial deformities,” said her mom, Lynn Anto.

After months of testing, Grace was given a list of diagnoses, which included coronal suture craniosynostosis, a premature fusing of bones in the skull, resulting in restricted skull growth.

Because of her condition, Grace has had – and will continue to have – multiple stays at Texas Children’s. She has had surgery to correct the misalignment of her eyes, and multiple visits to a craniofacial orthodontist who placed an expander in her mouth. There are also future plans for jaw surgery and braces.

Grace admits the surgeries are tough, “but you just have to get through it,” she said. Both she and her mom understand that surgeries are a fact of life for her and that they must remain strong for each other.

Despite her medical challenges, Grace lives life to the fullest. She is quick to answer questions about her condition and doesn’t let much stop her. She is involved in competitive dance, choir, piano and theatre. Her favorite subjects in school are math and science. Wise beyond her years, Grace makes an effort to live each day by the motto she coined, “Don’t let fear take over happiness!”

As a Torch Relay participant, you can choose to join the Texas Children’s team, create your team or be an individual walker. Participants who raise $40 or more will receive a 2018 Torch Relay T-shirt, medal and drawstring bag as a thank you for participating. Participants who raise $5,000 or more will be invited to join the Torchbearer Club and attend the Torchbearer Weekend, which annually honors our top fundraisers.

For additional information, visit Torch-Relay.org or email Camille Landry lclandry@texaschildrens.org.

Physicians and scientists at Texas Children’s Hospital are known for treating patients with some of the most complex pediatric medical conditions. They’re also known for helping patients with some of the rarest.

From July 18 to 22, 20 individuals with Robinow syndrome and their families came to Houston from across North America for the 25th Robinow Syndrome Foundation Convention and Medical Conference, which was hosted by Texas Children’s Hospital. This group of patients represented a large cohort – about 10 percent – of all currently documented cases of Robinow syndrome, an ultra-rare disorder that affects the development of many parts of the body, usually resulting in distinctive craniofacial features, skeletal and genitourinary abnormalities, and in some cases heart defects.

Because there are several genes associated with Robinow, the physical characteristics and their severity can vary between individuals, affecting their health and quality of life in different ways. To gain a better understanding of specific health needs, and to gain new insight into the genetic reasons behind the variance in symptoms, Texas Children’s physicians held a special research day as part of the conference.

The multidisciplinary effort was two years in the making and driven by the research of Texas Children’s clinical geneticist Dr. V. Reid Sutton and co-investigator, Dr. Claudia Fonseca, adjunct assistant professor of molecular and human genetics at Baylor College of Medicine, whose work together on Robinow recently garnered a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health.

“Our work with the Robinow Syndrome Foundation two years ago led to us being able to observe differences in individuals depending on which gene was causing the disorder,” said Sutton. “We were excited to host the event this year at Texas Children’s so we could follow up on initial studies, get new samples for research, and gather more detailed information on the differences in physical symptoms in the hope that we can improve care for these patients.”

Clinical and lab space was set aside specifically for the research day. Texas Children’s Child Life Department was on hand to direct families, assist with procedures, and alleviate any stress or anxiety with activities and fun ways to pass the time. For six hours, the patients and their families met individually with teams of physicians across six different disciplines, including urology, plastic surgery, psychology, endocrinology and genetics.

In addition to collecting new samples, Sutton also measured bone density in about half the patients using DEXA (dual-energy X-ray absorptiometry) scanning and high-resolution peripheral quantitative computed tomography at the Children’s Nutrition Research Center’s Body Composition Lab. Dr. Renata Maricevich from the Department of Plastic Surgery examined patients’ craniofacial symptoms, noting the health implications of structural deformities, particularly breathing and speech problems, and how surgical options could help. Additionally, a team of pediatric urology fellows and residents, led by Dr. Paul Austin, director of Texas Children’s Complex Urologic Reconstruction program and professor of Surgery for the Department of Urology at Baylor, observed patients’ genitourinary abnormalities, which can affect both appearance and function, particularly among males with Robinow.

“I anticipate the collaborative research conducted during the conference will culminate in a landmark reference document for the treatment of Robinow,” Austin said. “The specialty-specific data will help better characterize and delineate the phenotypic features based on the mutation present. So in the case of urology, we will have a better understanding of urologic issues associated with the various genetic forms of Robinow and will be able to develop more specialized treatments.”

In addition to possible surgical interventions, findings from the research day demonstrated that there could be potential non-surgical treatment options for Robinow patients as well. Dr. Shilpi Relan from pediatric endocrinology spoke to families about growth hormone therapies, as well as the possibility of testosterone therapy for males to help mitigate, or perhaps even avoid, some of the genitourinary symptoms. Experts at Texas Children’s also addressed the potential psychological repercussions of living with Robinow. Drs. Marni Axelrad and David Schwartz from Texas Children’s Clinical and Pediatric Health Psychology assessed cognitive and fine motor strengths and weaknesses, and created behavioral and emotional profiles for individual patients.

“Texas Children’s provides fabulous support for individuals living with syndromes like Robinow and their families,” Axelrad said. “Whether they need help for emotional, behavioral or cognitive challenges, our providers work together to better understand each patient and their needs. The information gathered at this conference has the potential to help patients understand how Robinow specifically affects them, as well as providing information about potentially helpful clinical assessment and intervention.”

The event was incredibly well received by the families who attended.

“The response from our families was very positive,” said Kimberly Kremeier, executive director of the Robinow Syndrome Foundation. “The physicians at Texas Children’s took time to explain in detail their findings and potential treatment plans. Our families were pleased to get answers, and some needing treatment now have a plan of care that hadn’t been available in their local communities. We welcome future collaboration with Texas Children’s in the future.”

The multidisciplinary research team will reconvene in the coming months to compile their findings from the research day, as well as presenting subsequent ideas for treatment and therapies, into manuscripts for joint publication.

“Ultimately we want to understand all the physical manifestations of Robinow in detail, as well as correlating the genetic basis in individual patients,” Sutton said. “Knowing why we’re seeing the physical differences is going to help us improve the care we can provide.”