Diabetes & Endocrinology

DNA molecule

New genetic cause of overgrowth syndrome caused by SPIN4 variant

DNA molecule

A researcher at Children’s National Hospital identified a new genetic cause of overgrowth syndrome in Spindlin Family Member 4 (SPIN4), an epigenetic reader, in which a loss-of-function variant in SPIN4 causes a prenatal onset of extreme tall stature in a male individual, inherited in an X-linked semi-dominant fashion.

Overgrowth syndrome is a rare genetic childhood disorder commonly caused by pathogenic genetic variants in epigenetic writers, such as DNA or histone methyltransferases. A researcher at Children’s National Hospital identified a new genetic cause of overgrowth syndrome in Spindlin Family Member 4 (SPIN4), an epigenetic reader, in which a loss-of-function variant in SPIN4 causes a prenatal onset of extreme tall stature in a male individual, inherited in an X-linked semi-dominant fashion.

The study, published in JCI Insight, reported Spin4 knockout pre-clinical models recapitulating human phenotype and found evidence that SPIN4 normally binds specific modified histone peptides, promotes canonical WNT signaling and inhibits cell proliferation in vitro and that the identified frameshift variant lost all of these functions.

How does this work move the field forward?

“These findings prove that SPIN4 negatively regulates mammalian body growth, and loss of SPIN4 causes an overgrowth syndrome in humans and pre-clinical models, expanding our knowledge of the epigenetic regulation of human growth and development,” says Youn Hee Jee, M.D., endocrinologist at Children’s National and co-senior author of the study.

What did you find that excites you?

SPIN4 is the first epigenetic reader gene identified to cause overgrowth syndrome in humans.

“Understanding the full characteristics of the phenotype caused by SPIN4 variants will greatly advance our knowledge in epigenetic regulation of childhood growth and SPIN4-associated disorders,” Dr. Jee says.

How is Children’s National leading in this space?

Dr. Jee is leading a follow-up translational study to dissect the precise underlying pathobiology of overgrowth syndrome due to SPIN4 mutations. Using the knowledge, the ultimate goal of her work is to develop novel interventional approaches to treat childhood growth disorders.

U.S. News Badges

Children’s National Hospital ranked #5 in the nation on U.S. News & World Report’s Best Children’s Hospitals Honor Roll

U.S. News BadgesChildren’s National Hospital in Washington, D.C., was ranked #5 in the nation on the U.S. News & World Report 2023-24 Best Children’s Hospitals annual rankings. This marks the seventh straight year Children’s National has made the Honor Roll list. The Honor Roll is a distinction awarded to only 10 children’s hospitals nationwide.

For the thirteenth straight year, Children’s National also ranked in all 10 specialty services, with eight specialties ranked in the top 10 nationally. In addition, the hospital was ranked best in the Mid-Atlantic for neonatology, cancer, neurology and neurosurgery.

“Even from a team that is now a fixture on the list of the very best children’s hospitals in the nation, these results are phenomenal,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “It takes a ton of dedication and sacrifice to provide the best care anywhere and I could not be prouder of the team. Their commitment to excellence is in their DNA and will continue long after I retire as CEO later this month.”

“Congratulations to the entire Children’s National team on these truly incredible results. They leave me further humbled by the opportunity to lead this exceptional organization and contribute to its continued success,” said Michelle Riley-Brown, MHA, FACHE, who becomes the new president and CEO of Children’s National on July 1. “I am deeply committed to fostering a culture of collaboration, empowering our talented teams and charting a bold path forward to provide best in class pediatric care. Our focus will always remain on the kids.”

“I am incredibly proud of Kurt and the entire team. These rankings help families know that when they come to Children’s National, they’re receiving the best care available in the country,” said Horacio Rozanski, chair of the board of directors of Children’s National. “I’m confident that the organization’s next leader, Michelle Riley-Brown, will continue to ensure Children’s National is always a destination for excellent care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

“For 17 years, U.S. News has provided information to help parents of sick children and their doctors find the best children’s hospital to treat their illness or condition,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “Children’s hospitals that are on the Honor Roll transcend in providing exceptional specialized care.”

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

The eight Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other two specialties ranked among the top 50 were cardiology and heart surgery, and urology.

woman getting blood draw

Recommendations for management of positive monosomy X on cell-free DNA screening

woman getting blood draw

In a study published in the American Journal of Obstetrics and Gynecology, researchers provide context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome (TS).

Non-invasive prenatal testing (NIPT) using cell-free DNA (cfDNA) is currently offered to all pregnant women regardless of the fetal risk. While this test has excellent value to screen for chromosomal abnormalities such as Down syndrome, the test has a much lower positive predictive value for sex-chromosome abnormalities such as Turner syndrome. In a study published in the American Journal of Obstetrics and Gynecology, researchers provide context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome (TS).

The manuscript was put together by the Turner Syndrome Special Interest Group (TS SIG) of the Pediatric Endocrine Society, chaired by Roopa Kanakatti Shankar, M.D., endocrinologist at Children’s National Hospital, along with other specialists including a gynecologist, maternal fetal medicine expert, cardiologists and pediatric endocrinologists.

The big picture

The field of NIPT using cfDNA testing has advanced considerably making it routine in the care of pregnant women and more couples are opting for it. This will lead to an increased detection of monosomy X overall — some of which may be true positives, but others may be false positives, or even an indicator of maternal TS rather than an affected fetus. This article discusses the changing landscape and provides an expert opinion on how to manage these scenarios.

How does this work move the field forward?

“We hope that this will increase provider knowledge and recognition of the pitfalls of NIPT as a screening test for sex-chromosome disorders such as monosomy X,” says Dr. Kanakatti Shankar. “It will also provide a framework for the next diagnostic steps, management and referrals that a provider may take to optimize care for both mother and child.”

How is Children’s National leading in this space?

Current guidelines for the care of individuals with TS throughout the lifespan do not specifically address management of individuals with a cell-free DNA screen positive for monosomy X.

“As chair of the TS Special Interest Group, I was able to lead this unique collaborative effort which we hope will lead to better understanding of NIPT results in the context of TS and for multispecialty providers to improve prenatal detection and timely care,” says Dr. Kanakatti Shankar.

Read more about the study, Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome.

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

coronavirus and DNA

Case study: COVID-19 patient with autoimmune adrenal insufficiency and hypothyroidism

coronavirus and DNA

This is the first report of a pediatric patient with COVID-19 who developed autoimmune thyroid and cortisol deficiency, although not confirmed that it was related or triggered by the COVID-19 infection.

There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link has been established. In a case study, published in Hormone Research in Paediatrics, researchers at Children’s National Hospital report a 14-year-old girl admitted with COVID-19 and symptoms of MIS-C who was then recognized to have autoimmune polyglandular syndrome (APS2). This is the first report of a pediatric patient with COVID-19 who developed autoimmune thyroid and cortisol deficiency, although not confirmed that it was related or triggered by the COVID-19 infection.

What this means

APS2 is rare in children and has an incidence of 1 in 20,000. Until now, there have only been reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19.

“The role of COVID-19 in the etiopathogenesis of APS2 in this case remains unclear,” says Myrto Flokas, M.D., endocrinology fellow at Children’s National Hospital and first author of the case study. “But we suspect that it may have contributed to the rapid progression and severe clinical manifestations of both adrenal insufficiency and hypothyroidism leading to the presentation akin to MIS-C.”

The hold-up in the field

COVID-19 has been reported to affect the immune system and may serve as a trigger for autoimmune diseases similar to other viral infections.

“This is a case-report and while we cannot draw any mechanistic conclusions or infer causality, it is the first pediatric report of an association,” says Roopa Kanakatti Shankar, M.D., endocrinologist at Children’s National and one of the authors of the case study.  “We hope it will contribute to this novel field as our understanding of COVID-19 and its myriad effects on the immune system is still evolving.”

Why it matters

This case will alert clinicians to be mindful of the association and similarities in presentation of adrenal insufficiency to MIS-C and consider adrenal crisis in the differential diagnosis of such a presentation.

You can read the full case study, New-Onset Primary Adrenal Insufficiency and Autoimmune Hypothyroidism in a Pediatric Patient Presenting with MIS-C, in Hormone Research in Paediatrics.

DNA strands

Whole genome sequencing solves precocious puberty case

DNA strands

By conducting whole-genome sequencing, doctors were able to discover the cause of a patient’s severe precocious puberty.

A true medical anomaly — a patient with severe precocious puberty starting in infancy later developed bilateral testicular tumors. Despite extensive testing at multiple other hospitals, no one had been able to understand the underlying cause of his precocious puberty. That is until now, through a study led by Andrew Dauber, M.D., M.M.Sc., chief of Endocrinology at Children’s National Hospital.

The hold-up in the field

Before receiving care at Children’s National, the patient’s diagnostic workup was limited by genetic testing modalities and the ability to enroll him in an innovative research protocol.

Moving the field forward

“We were able to enroll the patient in a research protocol that allowed them to sequence his whole genome,” says Dr. Dauber. “Both in a DNA sample from his blood as well as in a sample from one of his testicular tumors, which was being removed surgically.”

Dr. Dauber then performed an analysis of the genome data and found that the patient had a mutation in the luteinizing hormone receptor (LHR), which was present in the testicle but not in his blood. This is called a somatic mutation. The LHR receives the signal from the pituitary gland, which tells the testicle to make testosterone. In this case, the LHR is always turned on, which makes him develop Leydig cell tumors in his testes, overproducing testosterone, causing him to have very early puberty.

By conducting whole-genome sequencing of the tumor and blood samples, the patient was confirmed to have bilateral, diffuse Leydig cell tumors harboring the somatic gain-of-function p.Asp578His variant in the LHCGR gene.

This mutation had been identified before in patients with isolated tumors but never in someone with diffuse bilateral tumors.

The patient benefit

By using cutting-edge genomic approaches, medical providers can identify unknown causes of endocrine disorders. It also stresses the importance of the clinical team working with translational researchers to determine answers for patients.

“With a more definitive diagnosis and understanding of what these tumors are, researchers can better counsel the family about the treatment options,” says Dr. Dauber. Other members of the Children’s National team that contributed to this work include Seth Berger, M.D., Ph.D.; Daniel Casella, M.D.; and Emmanuèle C Délot, Ph.D.

You can read the full study, Precocious Puberty in a Boy With Bilateral Leydig Cell Tumors due to a Somatic Gain-of-Function LHCGR Variant, in the Journal of the Endocrine Society.

girl monitoring blood sugar

Continuous glucose monitoring use patterns in young children after T1D diagnosis

girl monitoring blood sugar

Continuous glucose monitoring (CGM) is a blood glucose monitoring device worn on the body that is linked to positive glycemic outcomes in people with Type 1 diabetes

Continuous glucose monitoring (CGM) is a blood glucose monitoring device worn on the body that is linked to positive glycemic outcomes in people with Type 1 diabetes (T1D). However, very little research has examined CGM use and glycemic outcomes in young children, particularly those newly diagnosed with T1D.

A new Diabetes Technology and Therapeutics study led by Randi Streisand, Ph.D., C.D.C.E.S., Chief of Psychology and Behavioral Health at Children’s National Hospital, and others identified four meaningful trajectories of CGM use among young children across 18-months post-T1D diagnosis: those who “always” used CGM; those who got on CGM later but stayed on it (“late/stable”); those who used CGM inconsistently; and those who “never” used CGM. The investigators conducted a study of 157 parents of young children (1-6 years) newly diagnosed with T1D who enrolled in a behavioral intervention.

Importantly, the authors found that those with private insurance were more likely than those with only public insurance to be in the “always” and “late/stable” groups (as opposed to the “never” group). Those in the “always” and “late/stable” groups also had better glycemic outcomes than those in the “never group” at 18-months post-T1D diagnosis.

“This research highlights that insurance type can be a barrier to accessing CGM,” Dr. Streisand noted. “Further, this is one of the first studies, among newly diagnosed young children, to show that CGM initiation at diagnosis or near diagnosis followed by sustained use is associated with better glycemic outcomes compared to never initiating CGM, supporting findings from other studies conducted with older youth.”

The findings inform clinical care with patients as it suggests that, when clinically appropriate, CGM initiation near or at the time of diagnosis benefits glycemic outcomes in young children when followed by sustained use. This is the only study to examine patterns of CGM use among 1-6-year-old children newly diagnosed with T1D over the first 18-months post-diagnosis.

“It was exciting to find differences in glycemic outcomes based on CGM initiation and use in this unique population,” Dr. Streisand said. However, the authors concluded that, given the health benefits of CGM, further exploration of barriers to CGM access and use among some families is needed.

In addition to Dr. Streisand, other Children’s National co-authors include Carrie Tully, Ph.D.;  Maureen Monaghan, Ph.D., C.D.E., and Christine Wang, Ph.D.

Innovations for health equity: Food pharmacy app wins Hackathon

When families come into the endocrinology clinic, 66% of prediabetes and Type 2 diabetes patients screen positive for food insecurity. One remedy: a smartphone app envisioned by Children’s National Hospital researchers to communicate with families between visits and provide resources to help stock pantries with nutritious foods.

The Children’s National Food Pharmacy app is on its way from idea to reality, thanks to the inaugural Health Equity in Research Hackathon event at the Children’s National Research & Innovation Campus. This team-based, “Shark Tank”-like competition involved roughly 50 experts designing creative healthcare solutions that could be delivered through ubiquitous smartphones.

“It takes a village to raise a child, and we want to show that at Children’s National we are part of that community,” said food pharmacy founder and diabetes educator Alexis Richardson, M.S., R.D., L.D.N., C.D.C.E.S.

Why it matters

The rate of new-onset Type 2 diabetes increased by a staggering 182% during the first nine months of the COVID-19 pandemic. Now, the Children’s National food pharmacy provides families that screen positive for food insecurity during quarterly clinic appointments with a 50-pound bag of medically-tailored groceries.

The new app, as envisioned, would follow them home to connect them with food bank information and other nutritional resources, eliminating paper forms and other hurdles that get in the way of care.

What’s ahead

Children’s National leaders are committed to making the proposal a reality. “We are going to support today’s winner through the next steps to prepare them to enter the app development pipeline at the Sheikh Zayed Institute,” said Lisa Guay-Woodford, M.D., director for the Clinical and Translational Science Institute at Children’s National (CTSI-CN) and one of the main judges of the competition.

The app development will happen in the months ahead. Kevin Cleary, Ph.D., technical director of the Sheikh Zayed Institute of Pediatric Surgical Innovation, said the Hackathon planted the seeds. “It really depends on the drive of the individual to see the idea to fruition,” Cleary told competitors.

Other app entries were encouraged to continue their work:

  • The Surgical Checklist, led by Brian K. Reilly, M.D., co-director of the Cochlear Implant Program: this app would help patients and providers successfully navigate the often-confusing pre-operative checklist, including required physical exams, lab work, imaging and pre-procedure fasting. Reilly said the hospital handles about 15,000 cases a year, and about 10% are rescheduled, often for reasons that could be avoided with digital organization and reminders for families.
  • More than Determined, led by Pediatrician Jessica Lazerov, M.D., M.B.A.: this app aims to give time-strapped providers a platform to better understand and address social determinants of health – such as access to safe housing, education and jobs – that can promote better preventative care outcomes.

The Health Equity in Research Hackathon was created by the new Health Equity in Research Unit, a joint initiative between the CTSI-CN and the Center for Translational Research within the Children’s National Research Institute.

Dr. Lisa Guay-Woodford and the winners of the Health Equity in Research Hackathon

Dr. Lisa Guay-Woodford, director for the Clinical and Translational Science Institute, joins the winners of the inaugural Health Equity in Research Hackathon: the Children’s National Food Pharmacy. The team’s proposed app will connect families facing food insecurity with resources and guidance for nutritious eating.

iLet Bionic Pancreas

Multicenter trial finds bionic pancreas improves Type 1 diabetes management

iLet Bionic Pancreas

Compared to other available artificial pancreas technologies, the bionic pancreas requires less user input and provides more automation because the device’s algorithms continually adjust insulin doses automatically.

A device known as a bionic pancreas, which uses next-generation technology to automatically deliver insulin, was more effective at maintaining blood glucose levels within normal range than standard-of-care management among people with Type 1 diabetes, a new multicenter clinical trial found.

The trial, conducted partly at Children’s National Hospital, was primarily funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, and published in the New England Journal of Medicine.

Automated insulin delivery systems – also called artificial pancreas or closed-loop control systems – track a person’s blood glucose levels using a continuous glucose monitor and automatically deliver the hormone insulin using a pump. These systems replace reliance on insulin delivery by multiple daily injections, pumps without automation and testing glucose levels using more labor-intensive systems, such as fingersticks.

“A diagnosis of Type 1 diabetes can be overwhelming for a child and their family,” said Fran Cogen, M.D., C.D.C.E.S., principal investigator at Children’s National and director of the Childhood and Adolescent Diabetes Program. “It is extremely important to monitor and manage glucose levels throughout the day to prevent serious complications like eye problems, kidney disease, heart and blood vessel disease. This new technology may give patients and families a sense of relief from some of the daily stressors that come with the diagnosis of this chronic disease.”

Compared to other available artificial pancreas technologies, the bionic pancreas requires less user input and provides more automation because the device’s algorithms continually adjust insulin doses automatically. Users of the bionic pancreas also do not have to count carbohydrates, nor initiate doses of insulin to correct for high blood glucose. In addition, healthcare providers do not need to make periodic adjustments to the device’s settings.

The 13-week trial, conducted at Children’s National and 15 other U.S. clinical sites, enrolled 326 participants ages 6 to 79 years who had Type 1 diabetes and had been using insulin for at least one year. Participants were randomly assigned to either a treatment group using the bionic pancreas device or a standard-of-care control group using their personal pre-study insulin delivery method.

The study found:

  • In participants using the bionic pancreas, glycated hemoglobin improved from 7.9% to 7.3%, yet remained unchanged among the standard-of-care control group.
  • The bionic pancreas group participants spent 11% more time within the targeted blood glucose range compared to the control group.
  • Results were similar in youth and adult participants.
  • Improvements in blood glucose control were greatest among participants who had higher blood glucose levels at the beginning of the study.

Hyperglycemia caused by equipment problems was the most frequently reported adverse event in the bionic pancreas group. The number of mild hypoglycemia events and frequency of severe hypoglycemia were not different in the two groups.

“The results of this study will bring hope to patients, families and providers that there are technologies being created to help ease the burden of diabetes management and keep glucose levels more stable,” said Kimberly Boucher, M.S.H.S., B.S.N., R.N., clinical research manager of Endocrinology at Children’s National.

The study is one of several pivotal trials funded by NIDDK to advance artificial pancreas technology and look at factors including safety, efficacy, user-friendliness, physical and emotional health of participants, and cost. To date, these trials have provided the important safety and efficacy data needed for regulatory review and licensure to make the technology commercially available. The Jaeb Center for Health Research in Tampa, Florida, served as coordinating center.

Funding for the study was provided by NIDDK grant 1UC4DK108612 to Boston University, by an Investigator-Initiated Study award from Novo Nordisk, and by Beta Bionics, Inc., which also provided the experimental bionic pancreas devices used in the study. Insulin and some supplies were donated by Novo Nordisk, Eli Lilly, Dexcom and Ascensia Diabetes Care. Partial support for the development of the experimental bionic pancreas device was provided by NIDDK SBIR grant 1R44DK120234 to Beta Bionics, Inc.

You can read the full study, Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes, in the New England Journal of Medicine.

Mother helping son check blood sugar levels

Supporting parents and children through diabetes diagnosis

Mother helping son check blood sugar levels

Behavioral intervention can improve parents’ mood following their child’s diabetes diagnosis.

Results from a new study show that behavioral intervention improved parents’ mood following young children’s Type 1 diabetes diagnosis.

The study evaluated First STEPS, a stepped-care behavioral intervention designed to support parents’ psychosocial functioning and promote children’s glycemic outcomes. Results indicated likely benefits of parent coach support, supplemented by intervention intensifications, including behavioral intervention and diabetes education.

“We found that parent coaches, or parents of slightly older children with Type 1 diabetes who were trained in offering peer support, were helpful in reducing parent depressive symptoms up to one year and a half following diagnosis for parents in the stepped care group,” says Randi Streisand, Ph.D., C.D.C.E.S., Psychology and Behavioral Health division chief at Children’s National Hospital and senior author of the study. “The second study target, child glycemic control, was not significantly different between the two groups.”

What’s been the hold-up in the field?

There are unique challenges facing families of young children with Type 1 diabetes. However, typical care and management guidelines are not specific to young children.

“Many parents of children diagnosed with diabetes experience distress and symptoms of depression, yet parents are not routinely screened during clinic visits,” Dr. Streisand says. “Further, there are many barriers to mental health support.”

Moving the field forward

Findings also highlighted the potential for training lay people who have a shared lived experience (parent coaches), which could be incorporated into clinical programs.

Most behavioral interventions use behavioral health experts. The study’s experts demonstrated significant outcomes in parent mood by using parent coaches.

“The goal would be to incorporate parent coach programs into the clinic setting, to either offer the support to all families at the time of diagnosis or to screen families and provide support to those in need,” Dr. Streisand adds.

The authors affirm this model has high potential for patient engagement. Additionally, results showed that incorporating targeted behavioral support for intensive diabetes treatment may maximize intervention impact.

Other Children’s National authors include: Carrie Tully, Ph.D.; Christine Wang, Ph.D.; Lauren Clary, Ph.D.; Fran Cogen, M.D.; John Barber and Celia Henderson.

You can read the full study First STEPS: Primary Outcomes of a Randomized, Stepped-Care Behavioral Clinical Trial for Parents of Young Children With New-Onset Type 1 Diabetes in Diabetes Care.

US News Badges

Children’s National named to U.S. News & World Report’s Best Children’s Hospitals Honor Roll

US News BadgesChildren’s National Hospital in Washington, D.C., was ranked No. 5 nationally in the U.S. News & World Report 2022-23 Best Children’s Hospitals annual rankings. This marks the sixth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the sixth year in a row.

For the twelfth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“In any year, it would take an incredible team to earn a number 5 in the nation ranking. This year, our team performed at the very highest levels, all while facing incredible challenges, including the ongoing pandemic, national workforce shortages and enormous stress,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “I could not be prouder of every member of our organization who maintained a commitment to our mission. Through their resilience, Children’s National continued to provide outstanding care families.”

“Choosing the right hospital for a sick child is a critical decision for many parents,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings spotlight hospitals that excel in specialized care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

The seven Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other three specialties ranked among the top 50 were cardiology and heart surgery, gastroenterology and gastro-intestinal surgery, and urology.

DNA

New research on genetic evaluation of short stature, discussed by Andrew Dauber, M.D., M.M.Sc.

DNA

In this study, the authors at Shanghai Children’s Medical Center utilized next-generation sequencing (NGS) to analyze the data of patients with short stature to better understand the etiologies of short stature.

Andrew Dauber, M.D., M.M.Sc., division chief of Endocrinology at Children’s National Hospital, shared expert commentary on a recent study published in The Journal of Clinical Endocrinology & Metabolism that explores associated risk factors of short stature as identified by exome sequencing in children.

In this study, the authors at Shanghai Children’s Medical Center utilized next-generation sequencing (NGS) to analyze the data of patients with short stature to better understand the etiologies of short stature.

The big picture

“This was a large-scale study looking at 814 children with short stature and at least one more clinical feature suggestive of a genetic condition who underwent comprehensive genetic testing at Shanghai Children’s Medical Center,” explains Dr. Dauber. In this study, the authors identified a potential genetic etiology in 361 of the patients, which is 44% of the cohort.

“It is important to note that the yield of genetic testing was highly variable depending on the clinical presentation of the child,” said Dr. Dauber. “For example, patients with associated congenital anomalies or a suspected skeletal dysplasia had a diagnostic yield of 56% and 65% respectively, while patients with isolated severe short stature (defined as a height below -3 SDS) only had a yield of 11%.”

Dr. Dauber noted that the overall high yield is reflective of the types of patients who are referred to this specialty center, and the expected yield in a more general pediatric setting is likely much lower.

The patient benefit

“This study helps shed light on the prevalence of those patients in a large cohort of children presenting for evaluation of short stature,” shared Dr. Dauber. “I am hopeful that targeted treatments will improve growth in these children.”

While this study provides new insights into the underlying causes behind short stature in patients with differing phenotypes, the authors indicate that additional large-scale studies on short stature exome sequencing are warranted.

Moving the field forward

Dr. Dauber also pointed to the fact that the authors note a large number of the patients in this study had undiagnosed Rasopathies, such as Noonan syndrome. “There were also 31 patients with FGFR3 mutations, 6 patients found with ACAN (Aggrecan) mutations and 2 with NPR2 mutations,” said Dr. Dauber.

“At Children’s National, we are currently conducting a clinical trial of vosoritide, a novel growth promoting agent which targets the growth plate in children with selected genetic conditions including Noonan syndrome and patients with mutations in FGFR3, ACAN, and NPR2,” included Dr. Dauber. Preliminary results from this clinical trial were recently presented by Dr. Dauber at the Pediatric Endocrine Society annual meeting.

You can read the full study Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature in The Journal of Clinical Endocrinology & Metabolism.

doctor measuring girl's height

Vosoritide shows promise for children with certain genetic growth disorders

doctor measuring girl's height

This is the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature, including hypochondroplasia, Noonan syndrome, NPR2 mutations and Aggrecan mutations.

Andrew Dauber, M.D., M.M.Sc., endocrinologist at Children’s National Hospital, presented preliminary results from a phase II clinical trial of a new drug, vosoritide, used to treat children with certain growth disorders, at the Pediatric Endocrine Society annual meeting held virtually on May 1.

Vosoritide is a C-type natriuretic peptide analog that binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway.

This is the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature, including hypochondroplasia, Noonan syndrome, NPR2 mutations and Aggrecan mutations.

To date, 34 participants have enrolled in the trial with a median baseline height of -3.2 SD (interquartile range (IQR) -3.7, -2.6). 18 subjects have initiated on vosoritide and twelve have completed six months of therapy. The authors note that the mean increase in annualized growth velocity (AGV) was 1.8 cm/yr for subjects with hypochondroplasia and 6.1 cm/yr for subjects with Noonan syndrome or NPR2 mutations. The two subjects with NPR2 mutations had increased AGVs of 4.4 and 9.2 cm/yr, while the two subjects with Noonan syndrome had increased in AGVs of 7.5 and 3.3 cm/yr. One of the Noonan syndrome subjects was previously treated with growth hormone (GH) for 2 years and AGV was 6.7 cm/yr while on GH, 4.1 cm/yr during the trial 6-month observation period and 11.6 cm/year during the first six months of vosoritide treatment.

To the researchers, the safety profile is quite reassuring. So far, the preliminary results showed increased growth in all the genetic subgroups with the patients with hypochondroplasia demonstrating a response similar to that seen previously in patients with achondroplasia. While the results are very promising for patients with Noonan syndrome and NPR2 mutations, the clinical trial must be completed before drawing further conclusions. The experts also plan to submit the study to a peer-reviewed journal in the future to validate the findings.

The big picture

This is the first medication that directly targets the pathway in chondrocytes (cells in the growth plate that make the bones grow longer) affected by these specific mutations. This means that the novel approach may give patients additional therapeutic options outside of growth hormone.

Why we’re excited

“These are the first patients in the world to ever receive this medication for their conditions,” said Dr. Dauber. “The results are very promising and may change the way we practice medicine. Patients have come from all over the world to participate in the study.”

Children’s National leads the way

This clinical trial funded by BioMarin is the first of its kind to treat children with genetic short stature who do not have achondroplasia. Children’s National is the only site in the world offering this therapy for patients with these conditions.

Find out more about the trial here.

Shideh Majidi

Shideh Majidi, M.D., M.S.C.S, brings focus on psychosocial research in diabetes patients to Children’s National

Shideh Majidi

Dr. Majidi specializes in Type 1 diabetes and has been involved in innovative research studying behavioral and psychosocial aspects of health care such as anxiety, depression and suicide and improving high-risk patient management for children with the disease.

Children’s National Hospital welcomes Shideh Majidi, M.D., M.S.C.S., as the new associate director of the Childhood and Adolescent Diabetes Program. Dr. Majidi specializes in Type 1 diabetes and has been involved in innovative research studying behavioral and psychosocial aspects of health care such as anxiety, depression and suicide and improving high-risk patient management for children with the disease.

Dr. Majidi comes to Children’s National from the Barbara Davis Center for Diabetes where, in addition to providing clinical care in the Pediatric Diabetes Division, she was the assistant professor of pediatric endocrinology, head of the depression screening and high-risk task force committees, developer and director of an online class for children managing their Type 1 diabetes and a member of several committees focusing on program evaluation and residency and fellowship recruitment.

When Andrew Dauber, M.D., M.M.Sc., took over the role of division chief of Endocrinology, his goal was to create a clinical endocrinology research program to provide cutting-edge treatment for families. Dr. Dauber is excited to have Dr. Majidi bring her expertise to the team to further this goal. “Dr. Majidi has played a key role in national cooperative research on quality improvement in pediatric diabetes care and is now leading an international collaborative focused on preventing suicide in individuals with Type 1 diabetes,” says Dr. Dauber. “Her compassion, intellect and commitment to improving care for all children with diabetes is an inspiration to us all.”

Dr. Majidi will continue to serve in her roles as site co-lead for Type 1 Diabetes Exchange Quality Improvement Collaborative, where she recently led a 2021 study exploring inequities in access to and outcomes of health care for those with Type 1 diabetes, and  co-chair for RESCUE, which aims to reduce suicide rates among individuals with diabetes.

She is dedicated to meeting patients and families where they are to help provide the best care. “We may think we see a lack of effort in diabetes care from patients and families, but we need to reframe our mindset and dig deeper to determine what barriers are in the way of diabetes management– behavioral, psychosocial or otherwise,” says Dr. Majidi. “When we do this, we can then work on how to help families manage and overcome the barriers that affect their diabetes care.”

aggrecan protein

Two new papers advance aggrecan deficiency research

aggrecan protein

Aggrecan (ACAN) is a large protein found in joint cartilage and growth plates.

Andrew Dauber, M.D., M.M.Sc., division chief of Endocrinology at Children’s National Hospital, and colleagues recently published two papers that describe the phenotypic spectrum of aggrecan deficiency and look at treating the condition with human growth hormone.

Aggrecan (ACAN) is a large protein found in joint cartilage and growth plates. It allows joints to move smoothly and without pain. Aggrecan deficiency — due to heterozygous mutations in the ACAN gene — causes dominantly inherited short stature and, in many patients, early-onset osteoarthritis and degenerative disc disease.

Clinical phenotype of patients with aggrecan deficiency

In 2017, Dr. Dauber led an international consortium of researchers that published a manuscript describing the phenotypic spectrum of 103 individuals – 70 adults and 33 children, including 57 females and 46 males – from 20 families with ACAN mutations. In the study, Dr. Dauber and his colleagues established that short stature and accelerated bone age is common among people with ACAN mutations.

In a new study published in the American Journal of Medical Genetics Part A, Dr. Dauber and colleagues further characterize the phenotypic spectrum of aggrecan deficiency, with an emphasis on musculoskeletal health.

Twenty-two individuals from nine families were enrolled in the study. Recorded histories and examinations focused on joint health, gait analysis, joint specific patient reported outcomes and imaging.

“We performed a detailed analysis of the musculoskeletal manifestations in patients with mutations in the aggrecan gene,” says Dr. Dauber. “We found that patients with mutations in this gene had significant short stature which worsened with age. There was a high prevalence of joint complaints and arthritis in adults, and we were able to detect pre-symptomatic joint damage in children using knee MRIs.”

Treating short stature in aggrecan-deficient patients with human growth hormone

Until now, it was unknown how to treat children with aggrecan deficiency. “Providing growth hormone therapy to children with ACAN gene mutations is relatively new in the field of pediatric endocrinology,” explains Dr. Dauber. “Previously, the assumption was that this was just short stature.”

In a new study, published in The Journal of Clinical Endocrinology and Metabolism, Dr. Dauber and colleagues reported the results of a trial that evaluated the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency.

“This is the first prospective trial of growth hormone therapy in patients with mutations in the aggrecan gene,” says Dr. Dauber. “Mutations in the gene are the cause for short stature in approximately 2%  of individuals with idiopathic short stature.”

The open-label, single-arm, prospective study enrolled ten treatment-naïve patients with a confirmed heterozygous mutation in ACAN. Participants were treated with rhGH (50 µg/kg/day) over 1 year. Main outcomes measured were height velocity and change in height standard deviation score.

The authors found that growth hormone led to short term improvements in growth rate over the course of the year. The treated patients had their growth rate increase from 5.2 centimeters per year to 8.3 centimeters per year while on therapy.

In 2019, the researchers received the 2019 Human Growth Award at the Pediatric Endocrine Society’s Annual Meeting for an abstract related to this work, entitled “Clinical Characterization and Trial of Growth Hormone in Patients with Aggrecan Deficiency: 6 Month Data.”

Med Games Logo

Continuing medical education through online games

Med Games LogoAndrew Dauber, M.D., MMSc., chief of Endocrinology at Children’s National Hospital, participated as the faculty chair of a Med Games CME educational online activity, to provide continuing medical education for physicians. This game-based activity is intended to meet the educational needs of endocrinologists, endocrine fellows, primary care physicians, physician assistants, nurse practitioners and health care professionals who diagnose and manage children with growth hormone deficiency (CGHD). This CME educational program is provided by Med Learning Group and supported by an educational grant from Novo Nordisk Inc.

Learn more about the program and test your knowledge: ‘Accurate Diagnosis and Effective Management of Children with Growth Hormone Deficiency: What Can You Do to Improve Patient Outcomes in Your Clinical Practice?’

kale at the food pharmacy

Capital Area Food Bank and Children’s National launch food pharmacy program

kale at the food pharmacy

The goal of the food pharmacy program is to improve patient health by creating easy access to foods that help with the management of diabetes, and to reduce barriers to routine attendance at clinic appointments by co-locating food assistance with medical care.

Capital Area Food Bank and Children’s National Hospital launched a pilot program, hosted by the Diabetes and Endocrinology teams at Children’s National, that will enable children with prediabetes and diabetes who are experiencing food insecurity to leave their visits with nutritious groceries from an on-site “food pharmacy.”

“We know that good food and good health are deeply interconnected, especially for young people,” said Radha Muthiah, president and CEO of the Capital Area Food Bank. “For children whose families may not always have the resources to get a nutritious meal on the table, all kinds of health challenges can emerge, including diabetes. We’re proud to be partnering with Children’s National on an initiative that will enable brighter futures for kids by making healthy groceries available right at the point of care.”

The goal of the food pharmacy program is to improve patient health by creating easy access to foods that help with the management of diabetes, and to reduce barriers to routine attendance at clinic appointments by co-locating food assistance with medical care. Children diagnosed with prediabetes or diabetes (Types 1 and 2) who also screen positive for food insecurity are given a prescription for medically-tailored groceries, which can be filled immediately on site. The supply includes both produce and shelf-stable items. Families are also provided with information about where to find additional help obtaining food, along with nutrition education materials.”

Rates of type 2 diabetes and prediabetes in children have been rapidly increasing in the past years, partly a consequence of the epidemic of childhood obesity. These conditions disproportionally impact children of African and Hispanic descent and those coming from low-income families, according to Elizabeth Estrada, M.D., director of the Type 2 Diabetes Program at Children’s National Hospital.

“Healthy eating is crucial in the treatment and prevention of these conditions, but many of our families lack access to nutritious food,” said Dr. Estrada. “The partnership with the Capital Area Food Bank to establish a food pharmacy within the diabetes clinic allows us to not only help our patients and families with recommendations for healthy eating, but also provides them with the foods they need to prepare nutritious meals.”

Through the initiative, the Capital Area Food Bank and Children’s National aim to reach up to 120 unique families per month, providing each household with 35 pounds of food per visit over the course of a year.

insulin pump

Diabetes technology use in the cystic fibrosis community

insulin pump

Although diabetes technologies are associated with improvements in glycemic control and health-related quality of life among people with type 1 diabetes (T1D), the use and perceptions of continuous glucose monitors (CGM) and insulin pumps within the cystic fibrosis (CF) community have not been well documented.

In a recent study published in Diabetes Technology & Therapeutics, Brynn Marks, M.D., MS-HPEd, and co-authors, found that compared to T1D, rates of sustained diabetes technology use in the cystic fibrosis-related diabetes (CFRD) community are low, despite perceived benefits. The authors conclude that better insurance coverage to mitigate cost, better patient education and confirmation that these technologies improve health and patient-reported outcomes may increase uptake.

Read the full article in Diabetes Technology & Therapeutics.

doctor taking blood sample from child

Study shows increase in diabetes cases during COVID-19 pandemic

doctor taking blood sample from child

A retrospective study found pediatric Type 1 diabetes cases rose 15.2% and Type 2 diabetes cases increased by 182% during the first year of the COVID-19 pandemic compared to the prior two years— affecting non-Hispanic Black youth the most.

While the effects of COVID-19 on diabetes-related outcomes are extensively studied in adults, data about the incidence and severity of presentation of pediatric new-onset Type 1 diabetes (T1D) and Type 2 diabetes (T2D) is limited. A new retrospective study of 737 youth diagnosed with diabetes at Children’s National Hospital between March 11, 2018 and March 10, 2021 found pediatric T1D cases rose 15.2% and T2D cases increased by 182% during the first year of the COVID-19 pandemic compared to the prior two years — affecting non-Hispanic Black youth the most.

The study, published in Hormone Research in Paediatrics, compared T1D and T2D cases during the first 12 months of the pandemic, between March 11, 2020 and March 10, 2021, to the same time in the previous two years. This increase in cases was accompanied by a nearly six-fold rise in diabetic ketoacidosis (DKA) and a 9.2% incidence of hyperosmolar DKA during the pandemic as compared to no cases in the two years prior.

“A better understanding of the impact of the COVID-19 pandemic is crucial for raising public awareness, shaping policy and guiding appropriate health screenings,” said Brynn Marks, M.D., M.S.H.P.Ed., endocrinologist at Children’s National and lead author of the study.

Children’s National provides clinical care to approximately 1,800 youth with T1D and 600 youth with T2D annually. In the two years before the pandemic, cases of T2D accounted for 25.1% of all newly diagnosed diabetes at Children’s National compared to 43.7% during the pandemic. Before the pandemic, females accounted for 59.6% of youth with new-onset T2D but 58.9% of new-onset T2D cases were among males during the pandemic.

The researchers noted that the rise in cases of T2D and severity of presentation of both T1D and T2D during the pandemic disproportionately impacted non-Hispanic Black youth (NHB). NHB youth accounted for 58% of cases of T2D pre-pandemic, which further increased to 77% during the pandemic. The findings also showed that cases of DKA among NHB youth newly diagnosed with T1D increased during the pandemic compared to the two years before (62.7% vs. 45.8%, p=0.02).  Before the pandemic, there was no significant difference in A1c at T1D diagnosis between racial and ethnic groups. However, during the pandemic, hemoglobin A1c levels were higher among NHB youth.

“Future studies are needed to understand the root cause of the disproportionate impact of the COVID-19 pandemic on non-Hispanic Black youth with newly diagnosed diabetes,” said Dr. Marks. “These outcomes during the pandemic will likely worsen pre-existing health care disparities among youth with diabetes.  In understanding the indirect effects of our response to the pandemic, we can better inform future emergency responses and develop strategies to improve outcomes for all youth living with diabetes.”

Blood sample tube for anti-Müllerian hormone

A look at the clinical utility of anti-Mullerian hormone

Blood sample tube for anti-Müllerian hormone

Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance (MIS), is a hormone produced exclusively in the gonads. It was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females.

In a mini-review published in The Journal of Clinical Endocrinology and Metabolism, Roopa Kanakatti Shankar, M.D., pediatric endocrinologist at Children’s National Hospital and an associate professor of pediatrics at the George Washington University School of Medicine and Health Sciences, and co-authors offer an updated synopsis on AMH and its clinical utility in pediatric patients.

The authors performed a systematic search for studies related to the physiology of AMH, normative data and clinical role in pediatrics. After reviewing 70 clinical studies and systematic reviews, they conclude that, “AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child.”

Other authors from Children’s National Hospital include Andrew Dauber, M.D., MMSc, Tazim Dowlut-Mcelroy, M.D., and Veronica Gomez-Lobo, M.D.

Read the full review in The Journal of Clinical Endocrinology and Metabolism.