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.

September 10, 2018

Texas Children’s Hospital has been recognized as a Clinical Research Center of Excellence (COE) for CDKL5 Deficiency Disorder and is one of only five pediatric institutions in the country to receive this honor.

The International Foundation for CDKL5 Research selected Texas Children’s and its academic partner Baylor College of Medicine as a Center of Excellence for its medical expertise and extensive clinical research experience in the field of Rett syndrome and Rett-related disorders including CDKL5 Deficiency Disorder.

“It’s an honor for our hospital to be chosen as a center of excellence for CDKL5 deficiency disorder research,” said Dr. Bernhard Suter, who is the director of the CDKL5 Center of Excellence at Texas Children’s. “We look forward to collaborating with other centers across the country to accelerate CDKL5 research in order to provide the best care possible for these patients.”

Once considered an atypical form of Rett syndrome due to its overlapping symptoms and similar medical needs among patients with either condition, the symptoms associated with CDKL5 deficiency disorder and its genetic cause are distinct from those of Rett syndrome. CDKL5 deficiency disorder is now considered a separate condition.

The CDKL5 gene provides instructions for making a protein that is essential for normal brain development and function. When the CDKL5 gene is mutated, patients with CDKL5 deficiency experience a variety of symptoms including difficult-to-control seizures, repetitive hand movements and severe neuro-developmental impairment. Seizures usually begin within the first three months of life, and can appear as early as the first week after birth.

As a Center of Excellence, Texas Children’s multidisciplinary CDKL5 clinic (housed in our Rett Syndrome Clinic) provides comprehensive care to patients by allowing them to see several specialists in the same clinic visit – including neurology, genetics, GI, pulmonology, physical medicine and rehabilitation – resulting in more personalized treatment plans for newly diagnosed patients.

“After an extensive search of top notch medical facilities, we found that Texas Children’s Hospital was the perfect pairing of medical expertise and research initiatives into this condition that so tragically affects those suffering with CDKL5,” said IFCR President Karen Utley, who also is a parent of a child with CDKL5. “We are proud to partner with Texas Children’s Hospital in order to improve the quality of life and to find a cure for our children.”

July 17, 2018

On July 9, Texas Children’s Hospital and the Angelman Syndrome Foundation celebrated the official opening of the Angelman Syndrome Clinic at Texas Children’s, one of only seven Angelman syndrome-specific clinics in the United States – and the first in Texas.

Several patient families gathered on the 16th floor of Wallace Tower to attend the ribbon cutting ceremony. Debbie Sukin, the daughter of the late Dr. Ralph Feigin, delivered the opening remarks and shared how this new clinic will benefit her 16-year-old son Jacob and so many other children diagnosed with Angelman Syndrome.

“The hardest part of advocating and managing a child with Angelman Syndrome is trying to understand what might be wrong when they aren’t feeling right, looking right or acting right,” Sukin said. “We’re confident that this multidisciplinary clinic here at Texas Children’s will provide all children the expertise and best chance at meeting their maximum potential and provide guidance to ensure the best outcome.”

Occurring in one in 15,000 live births, Angelman syndrome is a neurogenetic disorder often misdiagnosed as autism or cerebral palsy that causes severe neurological impairment. Often times, these patients experience developmental delays, lack of speech, seizures, and walking and balancing disorders.

With the creation of this new clinic established through the generosity of donors and in partnership with the ASF, patients and their families now can access multiple specialists – experts in Angelman syndrome, clinical geneticists, neurologist, psychiatrist, speech language pathologist, genetic counselors and social work – in one setting rather than visiting multiple locations across the nation to manage and treat this disease.

“Thanks to the help of the ASF, we are proud to further our mission of providing very specialized care for patients with Angelman syndrome,” said Chief of Neurology Dr. Gary Clark. “Given the science that’s being developed at the NRI at Texas Children’s in genetics and neurology, we are making great strides in helping these patients.”

The ribbon cutting event also included remarks from Dr. Carlos Bacino, chief of the Angelman Syndrome Clinic, Carrie Rys, assistant vice president, and Eileen Braun, executive director of the Angelman Syndrome Foundation, whose organization donated $50,000 to advance Angelman syndrome research at Texas Children’s.

“Opening this clinic brings us one step closer to our commitment to establish a network of clinics across the country,” Braun said. “We could not be more proud to support Texas Children’s and their remarkable team of professionals in bringing this clinic to life. We look forward to impacting the lives of so many more families.”

Click here to learn more about our Angelman Syndrome Clinic at Texas Children’s.

June 26, 2018

Texas Children’s Hospital has once again been named as a national leader among pediatric institutions by U.S. News & World Report in their recently published 2018-19 edition of Best Children’s Hospitals.

Ranked fourth among all children’s hospitals nationally and one of only 10 hospitals to achieve the Honor Roll designation for the tenth straight year, Texas Children’s is the only hospital in Texas – and the entire Southern region of the U.S. – awarded this coveted distinction.

“Each year, our Texas Children’s team exhibits incredible strength and kindness, as well as passion, caring for the inspirational children and families we serve,” said Texas Children’s President and CEO Mark Wallace. “I believe this is one reason why we continue to maintain the respect and reputation as one of the best hospitals in the nation, and the destination for pediatric care in Texas.”

In addition to ranking children’s hospitals overall, U.S. News & World Report also ranks the top 50 pediatric hospitals in 10 major sub-specialty areas. To be considered for the honor roll distinction, a hospital must have high rankings in at least three sub-specialties. For the second straight year, Texas Children’s Heart Center ranks No. 1 in the nation for pediatric cardiology and heart surgery. Texas Children’s Pulmonology ranks as the best program in the country for children with lung diseases.

Texas Children’s has 8 subspecialties ranked in the top 10, and the hospital improved outcomes across all sub-specialties. There are approximately 190 children’s hospitals in the U.S. and this year, 86 of the 189 surveyed hospitals were ranked among the top 50 in at least one sub-specialty. The 2018-19 Best Children’s Hospitals Honor Roll recognizes the 10 hospitals with the highest rankings across all sub-specialties. Here are a few highlights of this year’s rankings for Texas Children’s:

  • Cardiology and Congenital Heart Surgery is again no. 1 in the nation and received the top score in externally reported risk-adjusted operative mortality for congenital heart surgery.
  • Pulmonology, which first debuted in the top spot in the 2016 rankings, is now again ranked no. 1 in the nation. We received the top score in several asthma outcomes and structure metrics, such as mean LOS for asthma patients.
  • Neurology and Neurosurgery moved from no. 4 to no. 3, receiving the top score in several outcomes metrics, such as 30-day readmissions for craniotomy and Chiari decompression and complication rate for epilepsy surgical procedures.
  • Nephrology also moved from no. 4 to no. 3, with the top score in one-year kidney transplant graft survival and hemodialysis catheter-associated bloodstream infections.
  • Urology moved from no. 6 to no. 4, propelled by the top score in unplanned hospital admission for urologic issues within 30 days of surgery, as well as significant improvements in hypospadias and revision surgeries.

Texas Children’s, working closely with our academic partner Baylor College of Medicine, continues to pioneer advancements in pediatric health care and earns the U.S. News honor roll distinction by being ranked among America’s best in:

  • #1 Cardiology and Congenital Heart Surgery
  • #1 Pulmonology
  • #3 Neurology and Neurosurgery
  • #3 Nephrology
  • #4 Gastroenterology and GI surgery
  • #4 Urology
  • #6 Cancer
  • #6 Diabetes and Endocrinology
  • #15 Orthopedics
  • #21 Neonatology

This year’s rankings are the results of a methodology that weighs a combination of outcome and care-related measures such as nursing care, advanced technology, credentialing, outcomes, best practices, infection prevention and reputation, among others.

“From a measurement perspective, our survey results demonstrate how hard we’re working as an organization to deliver high quality care to our patients,” Wallace said. “The more consistently we deliver high quality care and the safer we deliver that care to our patients, the better their outcomes are, and the better our overall numbers are.”

Our results continue to reflect the diligent efforts of a solid structure focused on the U.S. News survey. The process of compiling and refining our data is an ongoing challenge, which will continue to improve under the excellent leadership of Trudy Leidich, Elizabeth Pham and the entire USNWR team.

The 2018-19 edition of Best Children’s Hospitals is available online at www.usnews.com/childrenshospitals.

June 12, 2018

As Texas Children’s continues to expand its physical footprint as a leader in pediatric care, Texas Children’s Neurology Program is growing by leaps and bounds. As one of the largest pediatric neurology service providers in the nation, more than 30,000 patient encounters occur each year at Texas Children’s Neuroscience Center.

Ranked No. 4 nationally in neurology and neurosurgery by U.S. News & World Report, patients are treated for a number of neurological conditions in our 13 specialty clinics including epilepsy, cerebral palsy, Rett syndrome, Batten disease and movement disorders. Many patient families are referred to Texas Children’s for our integrated expertise and multidisciplinary team approach in diagnosing and treating childhood neurological disorders. Recently, the Neurology division expanded its services with the opening of the Angleman Syndrome Clinic to treat children with this very rare, neurogenetic disorder.

“Over the last decade, our neuroscience programs have experienced phenomenal growth,” said Chief of Neurology and Developmental Neuroscience Dr. Gary Clark. “In 2004, the division had 5,000 patient encounters per year. Since then, we have more than quadrupled our patient encounters to 31,500 in 2017. More than half of these patients are seen in the community, allowing for greater access to care.”

In 2017, the neurology service received 1,300 new patient referrals each month which is a 30 percent increase from last year. To meet the increased demand for these services and to accommodate the growing patient population, the pediatric neurology division faculty expanded from 9 to 52 neurologists.

While enhancing access to patient care remains a top priority for Texas Children’s, one way the Neurology service is helping to achieve this collaborative milestone is through the implementation of telemedicine, an interactive telecommunications system that uses real-time video technology to link patients with their primary care and specialty providers. Instead of making the trek to the Texas Medical Center, patients can now “see” their neurologist without ever leaving their primary care clinic.

“Through an HRSA grant, we have seen children with epilepsy in one of our medical homes via this new technology and completed more visits than any other grant recipient,” said Brian Cordasco, practice administrator for Neurology. “This successful experiment will serve as a blueprint for future growth of telemedicine at Texas Children’s. Six faculty offices are now equipped with telemedicine capabilities.”

To balance outpatient services with the increasing demand for inpatient care, the Neurology Service has also developed an inpatient service rotation for physicians at Texas Children’s Hospital West Campus. Just like Texas Children’s Medical Center Campus and Texas Children’s Hospital The Woodlands, neurologists and epileptologists take turns working out of clinic to take neurology consults at the hospital.

Partnerships advance clinical research in neurology

The neurology division’s partnership with the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s under the leadership of Dr. Huda Zoghbi also has helped to advance clinical and basic science research leading to the development of new treatments for neuro and developmental disabilities.

Nearly $185 million has been raised to build and partially endow the NRI, and the hospital’s long-time philanthropic partner, The Blue Bird Circle, has raised funds (initial gift $1M for four years) to form and partially endow the Blue Bird Circle Clinical Research Center in which NRI discoveries are realized through clinical trials.

The Blue Bird Circle has been the catalyst for so much of what has happened in pediatric neurology in the past 20 years at Texas Children’s. Clinical research protocols have grown from 9 to 63 over the 8-year existence of the Blue Bird Circle CRC. The Blue Bird Circle has raised in excess of $1.2 million annually to directly fund clinical treatment, training and research in pediatric neurology at Texas Children’s.

Through these collaborative research partnerships, the neurology team has made significant progress:

  • Texas Children’s is one of the few sites in the country that provides therapy to patients with an enzyme deficiency in the form of Batten disease by surgically injecting the synthesized enzyme directly into the brain thereby halting this degenerative form of Batten disease.
  • Texas Children’s treats patients with spinal muscular atrophy, a disease where the spinal cord degenerates due to a defective SMN1 gene. This treatment involves injecting a DNA molecule into the spinal fluid that turns a latent gene into an effective one that makes the deficient protein.

“We are contemplating similar treatments for Angelman and Rhett syndromes,” Clark said. “We are so grateful to Texas Children’s Blue Bird Circle Research Center in collaboration with the Jan and Dan Duncan Neurological Research Institute at Texas Children’s for helping us make these research breakthroughs possible, and I am excited about what the future will hold for pediatric neurology.”

February 13, 2018

For nearly 17 years, Maryann Macey has volunteered with the Blue Bird Circle Clinic for Pediatric Neurology at Texas Children’s Hospital – an opportunity that she describes as very rewarding.

“It is amazing to see all of the progress our organization has made in advancing research to help our physicians at the Blue Bird Circle Clinic diagnose and treat patients with neurological diseases,” Macey said. “It is an honor to be a Blue Bird volunteer and work with such an outstanding group of women.”

On February 6, Macey and 100 Blue Bird members including many of Texas Children’s employees, staff and leaders, attended a special luncheon at the Pavilion for Women to celebrate the Blue Bird Circle’s 95th birthday. The event included a $1.9 million check presentation from the Blue Bird Circle to Texas Children’s and Baylor College of Medicine. A large portion of this gift will support neuroscience research and training.

Since 1998, the Blue Bird Circle has supported the Clinic for Pediatric Neurology at Texas Children’s with millions of dollars in grants, as well as thousands of volunteer hours. Blue Bird volunteers devote countless hours at the Clinic and The Blue Bird Circle Resale Shop which has helped to raise awareness in the community about pediatric neurological disorders and highlight the incredible work being done at Texas Children’s to improve the quality of life for neurology patients.

“The words, “Blue Bird Circle,” are synonymous with its members’ generosity, volunteerism, commitment and dedication,” said Texas Children’s CEO Mark A. Wallace. “Members of the Blue Bird Circle have been the catalyst for so much of what has happened in pediatric neurology in the past 20 years. The care we provide, the research we conduct because of the Blue Birds benefit the patients we serve here and children with neurological conditions all over the world.”

During the luncheon, Dr. Gary Clark, Chief of Neurology and Developmental Neuroscience, spoke about the tremendous growth of the neuroscience program at Texas Children’s and shared examples of the research progress that has been made through our partnership with the Blue Bird Circle. To treat patients with an enzyme deficiency in the form of Batten disease, Texas Children’s is one of the few sites that provides therapy to these patients by surgically injecting the synthesized enzyme directly into the brain thereby halting this degenerative form of Batten disease. Texas Children’s also is using novel approaches to treat patients with spinal muscular atrophy, a disease of the nervous system where the spinal cord degenerates due to defects in the SMN1 gene. The treatment involves injecting a DNA molecule into the spinal fluid that turns latent gene into an effective one that makes the deficient protein.

“We are contemplating similar treatments for Angelman and Rhett syndromes,” Clark said. “We are so grateful to Texas Children’s Blue Bird Circle Research Center in collaboration with the Jan and Dan Duncan Neurological Research Institute at Texas Children’s for helping us make these research breakthroughs possible, and I am excited about what the future holds for pediatric neurology.”

Guest speakers at the event also included Dr. Charles Gay, medical director of Neurology at Texas Children’s Hospital West Campus, and Dr. Robert Zeller, medical director of the Blue Bird Circle Clinic for Pediatric Neurology. Texas Children’s Chief of Palliative Care Dr. Tammy Kang delivered the keynote address on the interdisciplinary palliative care program and how it supports patients and their families.

Prior to the luncheon, the Blue Bird members met with neurosurgeon Dr. Daniel Curry and Chief of Critical Care Dr. Lara Shekerdemian to tour different sections of the Legacy Tower which will open on May 22.

For more information about Blue Bird Circle, click here.

November 21, 2017

Six-year-old Molly Malinsky and her parents have a lot to be grateful for this holiday season. After their daughter was diagnosed with a seizure disorder at four months old, Molly is now seizure free, a miraculous outcome that her family credits to Texas Children’s world-class neuroscience team.

When the Malinskys learned that their daughter’s physician Dr. James Riviello – who had treated Molly since she was four months old – joined Texas Children’s as the associate section head for Epilepsy, Neurophysiology and Neocritical Care, it was a no brainer for the New Jersey family to travel to Houston to reunite with Riviello.

“Dr. Riviello is one of those amazing doctors who is not only knowledgeable, well respected and professional, but above all, cares deeply about his patients and their families,” Rebecca Malinsky said. “We followed Dr. Riviello from NYU to Columbia and now to Texas Children’s so our daughter would continue to receive the best care.”

When Molly was first diagnosed with epilepsy, she was prescribed seizure medication which seemed to work. Molly had no seizures for over a year, but when she was weaned off of her medication, Molly’s seizures returned. “The seizures were getting worse and more frequent,” Malinsky said. “My daughter would have 15 seizures in an hour and three to five seizures at school even when she was back on her medication, which was very scary.”

After five failed medication trials, the only option remaining for Molly was brain surgery. After her parents met with Riviello, Chief of Neurosurgery Dr. Howard Weiner, and neurosurgeon Dr. Daniel Curry to discuss Molly’s treatment plan, the team determined Molly would be a good candidate for brain surgery.

On October 26, 2017, Molly underwent laser ablation surgery, a minimally invasive procedure pioneered by neurosurgeons at Texas Children’s that uses an MRI-guided laser probe to identify and destroy lesions deep in the brain that cause seizures. As the first hospital to perform laser ablation surgery in 2010, Texas Children’s has performed more than 150 of these surgeries, making it possible to treat some of the toughest cases of epilepsy, and put the brakes on damaging seizures.

“The results are very diagnosis and patient specific,” said Curry, director of Pediatric Surgical Epilepsy and Functional Neurosurgery, who pioneered and performed the laser ablation surgery on Molly. “But for something like hypothalamic hamartoma, a particularly difficult disease to treat, it has taken success rates in curing the child’s seizures from under 50 percent to about 80 to 90 percent, so it’s been a significant change.”

MRI-guided laser ablation has not only increased the safety of epilepsy surgery, especially in cases where the targets are far from the surface of the brain, but has drastically improved recovery time. Many children go home the next day after surgery, seizure free. For Molly’s parents, their daughter’s outcome is truly remarkable.

“Since Molly’s surgery almost a month ago, she has not had a single seizure,” Malinsky said. “Her behavior has improved, her ability to learn and retain information at school has returned. Our daughter was able to go trick or treating for Halloween just four days after her brain surgery, which was pretty amazing.”

The Malinskys will return to Texas Children’s in February for Molly’s three-month followup. Meanwhile, they are grateful to Drs. Riviello, Curry and Weiner, and the hospital’s entire neurology and neurosurgery teams for the exceptional level of care, compassion, professionalism and teamwork they delivered to their daughter.

“Between our first visit to Texas Children’s in August and Molly’s surgery, everyone treated our daughter with compassion and offered ways to be helpful in the immediate and distant future as Molly’s treatment plan began to unfold,” Malinksy said. “I could not imagine this journey without the shared and genuine support of Texas Children’s amazing Neurology and Neurosurgery teams. Clearly, you have recruited the best doctors in the country.”

Click here to learn more about Texas Children’s Comprehensive Epilepsy Program and laser ablation surgery.