Tag Archive for: Shankar

Dr. Andrew Dauber measures Mia's height

First global clinical trial achieves promising results for hypochondroplasia

Dr. Andrew Dauber measures Mia's height

Trial participant Mia Maric is measured by Dr. Andrew Dauber.

Researchers from Children’s National Hospital presented findings from the first clinical trial of the medication vosoritide for children with hypochondroplasia – a rare genetic growth disorder. The results were presented at the 2024 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting.

The big picture

Recently approved to increase linear growth and open growth plates in children with achondroplasia, vosoritide is a C-type natriuretic peptide analog that binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation by inhibiting the ERK1/2-MAPK pathway.

“Vosoritide directly targets the pathway in the growth plate that is affected by the genetic mutation causing hypochondroplasia,” said Andrew Dauber M.D., M.M.Sc., chief of Endocrinology at Children’s National and lead author of the study.

During the phase 2 trial, researchers found vosoritide increased the growth rate in children with hypochondroplasia, allowing them to grow on average an extra 1.8 cm per year.

The patient benefit

Ivan Maric’s 11-year-old daughter, Mia, has been participating in the trial for the last 18 months. In 2022, they moved from Croatia to be part of the study.

“This has been life-changing for Mia,” Maric said. “Soon after receiving the initial doses, we immediately noticed growth. Now, she can independently manage everyday tasks such as washing her hair and reaching the sink to wash her hands.”

What’s next

Vosoritide treatment may work as a precision therapy to improve growth in multiple genetic conditions that interact with the ERK1/2-MAPK pathway.

“This study provides a proof of principle that this medicine will work for these children and supports further research in this area,” said Dr. Dauber. “I was excited to see how well tolerated the medication was and how some patients had excellent responses.”

This clinical trial funded by BioMarin is the first-of-its-kind to treat children with genetic short stature who do not have achondroplasia. Other growth-related conditions included in this phase 2 trial were Noonan syndrome, NPR2 mutations and Aggrecan mutations.

Additional authors from Children’s National: Anqing Zhang, Ph.D., Roopa Kanakatti Shankar, M.D., Kimberly Boucher, R.N., Tara McCarthy, B.A., Niusha Shafaei, B.A., Raheem Seaforth, B.A., Meryll Grace Castro, M.S., and Niti Dham, M.D.

mother hugging daughter

In the News: Earlier signs of puberty and the challenges faced

mother hugging daughter

“In many circumstances, access to care for precocious puberty has the same issue that we have with access to healthcare in general. Many of these children may not get care in a timely manner.”

Roopa Kanakatti Shankar, M.D., M.S., pediatric endocrinologist, spoke to NBC News about the uptick in early puberty and the importance of access to care for those who need treatment. Read her interview with NBC News.

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.

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.

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.

Clinic Level 4 Regional Resource Center Badge

Turner Syndrome Clinic designated as Level 4 Regional Resource Center

Clinic Level 4 Regional Resource Center Badge

The Children’s National Hospital Turner Syndrome Clinic is proud to be recognized by the Turner Syndrome Global Alliance (TSGA) as a Level 4 Regional Resource Center. Level 4 is the highest Level of Care designation and is based on the KidNECT Care Model which encourages family networking, education, comprehensive coordinated care and transition support as well as leadership in Turner Syndrome (TS) research.

TS is a rare genetic disorder that occurs in 1 to about 2,500 girls and is caused by a partial or complete missing X chromosome. Some of the characteristics of TS are short stature, delayed puberty, kidney, thyroid and heart problems. Although there is no cure for TS, many of the symptoms can be treated.

The Children’s National TS Clinic is part of the Division of Endocrinology and Diabetes which is ranked by U.S. News & World Report as one of the top 10 programs in the nation. The TS Clinic opened in January 2019 and is the first one-of-its-kind in the Washington, D.C. region. A multidisciplinary clinic is held once a month with the team comprising of cardiology, endocrinology, psychology, gynecology and genetics to help care for the needs of patients with TS all in one day. The referral network of specialties includes neuropsychology, otolaryngology, audiology, orthopedics, urology and dentistry.

“I am so proud of our team for their hard work and the excellent clinical care they provide for girls with Turner Syndrome,” says Roopa Kanakatti Shankar, M.D., endocrinologist at Children’s National. “This recognition by the Turner Syndrome Global Alliance means that we not only provide comprehensive care but also serve as a regional leader and resource center for the families we serve. We will continue to raise awareness about Turner Syndrome through our research and partnerships.”

little girl being examined by doctor

First Washington-based Turner syndrome clinic opens Jan. 28

little girl being examined by doctor

Endocrinologists at Children’s National work with a team of cardiologists, gynecologists, geneticists, psychologists and other clinicians to provide comprehensive and personalized care for girls with Turner syndrome.

Starting Monday, Jan. 28, 2018 girls with Turner syndrome will be able to receive comprehensive and personalized treatment at Children’s National Health System for the rare chromosomal condition that affects about one in 2,500 female births.

Many girls with Turner syndrome often work with a pediatric endocrinologist to address poor growth and delayed puberty, which may be treated with human growth hormone and estrogen replacement therapy. They may also need specialty care to screen for and treat heart defects, frequent ear infections, hearing loss, vision problems and challenges with non-verbal learning.

Roopa Kanakatti Shankar, M.D., M.S., a pediatric endocrinologist at Children’s National, aims to consolidate this treatment with a comprehensive Turner syndrome clinic.

“We’re creating a place that girls with Turner syndrome can come to receive specialized and personalized treatment, while feeling supported,” says Dr. Shankar.

Patients can now schedule visits and meet with multiple specialists in one clinic location:

The multispecialty referral team includes neuropsychologists, otolaryngologists (ear, nose and throat doctors), orthopedics, urology and dentistry to address unique medical needs. Families can also schedule appointments with audiology and get labs and other studies on the same day.

As girls with Turner syndrome age, they are at increased risk for diabetes, an underactive thyroid and osteoporosis, which is one reason Dr. Shankar wants to educate and increase awareness early on.

“There is something special about girls with Turner syndrome,” says Dr. Shankar. “They are very inspiring and endearing to work with,” she adds, reflecting on her past research and future goals with the clinic. “Their perseverance in the face of challenges is one of the things that inspires me to work in this field.”

The Turner syndrome clinic at Children’s National meets the criteria for a level 2 clinic designation by the Turner Syndrome Global Alliance by providing coordinated medical care, same-day visits with multiple specialists and connecting patients with advocacy groups.

Within the next two years, Dr. Shankar looks forward to meeting level 4 criteria, the designation for a regional resource center, by adding multi-institutional research partners, mentoring programs and organizing a patient-family advisory council.

“As we start out, we aim to provide excellent clinical care and create a database while forming these partnerships, and over time, we hope this information will influence future research studies and foster a greater depth of tailored care,” says Dr. Shankar. “Our ultimate goal is to treat, support and empower girls with Turner syndrome to achieve their full potential.”

To learn more about the Turner syndrome clinic, available on the fourth Monday of every month, visit ChildrensNational.org/endocrinology.