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facial recognition of noonan syndrome

Commercialization of novel facial analysis technology can improve diagnosis of rare disorders in pediatric patients

facial recognition of noonan syndrome

Children’s National Hospital has entered into a licensing agreement with MGeneRx Inc. for its patented pediatric medical device technology using objective digital biometric analysis software for the early and non-invasive screening of dysmorphic genetic diseases such as Noonan syndrome.

Children’s National Hospital has entered into a licensing agreement with life sciences technology company MGeneRx Inc. for its patented pediatric medical device technology using objective digital biometric analysis software for the early and non-invasive screening of dysmorphic genetic diseases. The technology, developed by a multidisciplinary Children’s National team led by Marius George Linguraru, D.Phil, M.A., M.Sc., of the Sheikh Zayed Institute for Pediatric Surgical Innovation and Marshall Summar, M.D., director of the Children’s National Rare Disease Institute (CNRDI), can provide a more advanced diagnostic tool for regions of the world with limited access to geneticists or genetic testing.

The application utilizes artificial intelligence (AI) and machine learning to analyze biometric data and identify facial markers that are indicative of genetic disorders. Physicians can capture biometric data points of a child’s face in real time within the platform, where it scans facial biometric features to determine the potential presence of a genetic disease, which can often be life-threatening without early intervention. Research studies conducted in conjunction with the National Human Genome Research Institute at the National Institutes of Health further enhanced the development of the application in recent years, showing the potential to detect, with a 90 percent accuracy, early diagnosis of 128 genetic diseases across pediatric subjects in 28 countries. These diseases include DiGeorge syndrome (22q11.2 deletion syndrome), Down syndrome, Noonan syndrome and Williams-Beuren syndrome.

“We are delighted to enter into this licensing agreement through Innovation Ventures, the commercialization arm of Children’s National Hospital, which seeks to move inventions and discoveries from Children’s National to the marketplace to benefit the health and well-being of children. Our mission is to add the ‘D’ in development to the ‘R’ in research to accelerate the commercialization of our intellectual property,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National and managing director of Innovation Ventures. “It is through partnerships with startups and the industry that we can achieve this goal and thus we highly value this new partnership with MGeneRx Inc. The acceleration and commercialization of this objective digital biometric analysis technology will not only help diagnose rare genetic disorders – it will also allow for earlier interventions that improve the quality of life for the children living with these conditions.”

Eskandanian adds that the social impact of this technology is especially profound in lower income nations around the world, where there is a high prevalence of rare genetic conditions but a severe lack in the specialty care required to diagnose and treat them. Additional data collected through the expanded use of the technology will help to further develop the application and expand its capabilities to identify and diagnose additional rare genetic conditions.

The licensing agreement was arranged by the Children’s National Office of Innovation Ventures, which is focused on the commercialization of impactful new pediatric medical device technologies and therapies to advance children’s health care. Created to catalyze the ongoing translational research of the Children’s National Research Institute (CNRI) as well as inventions by hospital’s clinicians, Innovation Ventures focuses on four core pillars to advance pediatric medical technologies including a Biodesign program, partnerships and alliances to augment internal capacity, seed funding to de-risk technologies and validate market and clinical relevance, and back-office operations to manage intellectual property and licensing activities. Since 2017, Children’s National intellectual property has served as the basis for over 15 licensing or option agreements with commercial partners.

Providing access to an array of experts and resources for pediatric innovators is one of the aims of the Children’s National Research & Innovation Campus, a first-of-its-kind focused on pediatric health care innovation, with the first phase currently open on the former Walter Reed Army Medical Center campus in Washington, D.C. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on-site incubator Johnson and Johnson Innovation – JLABS, the campus provides a rich ecosystem of public and private partners, which will help bolster pediatric innovation and commercialization.

Natasha Shur

NORD names Natasha Shur, M.D., as hero of rare disease

Natasha Shur

Dr. Shur has a career working as a clinical geneticist for over a decade. She has been a part of the Children’s National community for more than two years. Dr. Shur as well serves as the lead for the Telemedicine Genetics Program under the Rare Disease Institute.

For her advancements in telemedicine genetics and rare diseases, Medical Geneticist Natasha Shur, M.D., received the 2021 Rare Impact Award from the National Organization for Rare Disorders (NORD). The recognition is the highest honor given to individuals that developed exceptional work benefiting the rare disease community.

“Despite the pandemic and the challenges we have faced, there are still heroes to be found among us from whom we can draw inspiration and motivation to keep moving forward,” said Peter L. Saltonstall, NORD president and CEO.

Given her involvement with several innovative projects at Children’s National Hospital, Dr. Shur built an active in-home telemedicine program where patients are being seen for first visits and follow-ups. Her work is helping families, including those with autistic children.

“Recently, in our division, we have been talking a lot about the concept of ‘failing forward.’ The idea is to try new approaches. These methods may not work, but the status quo does not always work either,” said Dr. Shur. “Since we have such a supportive and wonderful group, we can try new ways of working and new models of care.”

During the pandemic, the division led by Marshall Summar,.M.D., also created a telehealth first model of care and augmented educational apps and opportunities. The goal was to ensure that patients with rare disease would not lose access to care. The medical geneticists, genetic counselors, dieticians and administrative team met daily and cohesively to explore and improve new clinical approaches in order to put patients and families first.

Dr. Shur has a career working as a clinical geneticist for over a decade. She has been a part of the Children’s National community for more than two years. Dr. Shur as well serves as the lead for the Telemedicine Genetics Program under the Rare Disease Institute.

The Rare Disease Institute recently opened its new location on the Children’s National Research & Innovation Campus, a first-of-its-kind pediatric research and innovation hub located in Washington, D.C. The campus will provide a unique, state-of-the-art home for clinical genetic and specialty services.

The Children's National Research & Innovation Campus

Children’s National Research & Innovation Campus welcomes Rare Disease Institute as first occupant

The Children's National Research & Innovation Campus

The Rare Disease Institute, which includes the largest clinical group of pediatric geneticists in the nation, focuses on developing the clinical care field of the more than 8,000 rare diseases currently recognized and advancing the best possible treatments for children with these diseases.

The Children’s National Research & Innovation Campus (RIC), the first-of-its-kind pediatric research and innovation hub located in Washington, D.C., now has its first occupant – the Rare Disease Institute (RDI).

The institute, which includes the largest clinical group of pediatric geneticists in the nation, focuses on developing the clinical care field of the more than 8,000 rare diseases currently recognized and advancing the best possible treatments for children with these diseases.

With the advent of advanced DNA sequencing, databanks, informatics, new technology, pediatric consortiums and global partnerships, clinical researchers have never been in a better position to diagnose and treat rare diseases. As this field of medicine continues to rapidly evolve, the benefits provided to patients, families, clinicians and researchers through its new home at the RIC will further accelerate the trajectory of rare disease from an academic specialty into a mainstream medical field.

Marshall Summar, M.D., director of the RDI and chief of the Division of Genetics and Metabolism at Children’s National, is well-known for pioneering work in caring for children diagnosed with rare diseases. He developed and launched the world’s first RDI at Children’s National in 2017, and it became the first Clinical Center of Excellence designated by the National Organization for Rare Diseases (NORD). Dr. Summar discusses how this move will positively impact treatment, services and discovery on a national level.

Q: What are the patient benefits of the move to the RIC?

A: Patients with genetic conditions spend a lot of time visiting the hospital. By creating an easy access environment that is designed around their needs, we can provide world-class care to the families we work with. We designed extensive telemedicine capacity into the clinic so we can continue to expand our digital reach to wider areas. The parking facility is also a huge plus for our families with mobility impairments. The garage is only steps away from the clinic entrance. The architectural team worked closely with the clinical team to create a patient-centric facility for a safe and positive experience.

Q: What are the research benefits of being on the RIC?

A: One of our core goals at the RIC was to create research “neighborhoods.” A focus of the first phase of the RIC occupancy is genetics and the RDI is the clinical manifestation of that focus. Having the clinical service that sees patients with genetic disease, sharing space and campus with the Center for Genetic Medicine Research team and the molecular genetics laboratory creates that thematic neighborhood. Some of the best basic science ideas and projects come from the clinical world. Close interaction between the clinicians and the scientists will enhance those “spark” encounters. In addition, the physicians in the RDI who do bench research are also part of the genetic medicine program which furthers these interactions.

Marshall Summar

Marshall Summar, M.D., director of the RDI and chief of the Division of Genetics and Metabolism at Children’s National.

Q: What would you say has been the most significant change to your field in the past decade?

A: The ability to access next-generation genetic sequencing for more and more of our patients. The percentage of patients who can get a meaningful diagnosis with these technologies increases every year. With these techniques, we are finding new links between genes and disease at the rate of 5-10 per week.

Q: What excites you most about the future of medical genetics and rare diseases?

A: Two things are really exciting to me. The first is the ability to diagnose more patients than at any time in history. The second is the rate at which new genetic/rare disease therapies are being developed (around 50% of the FDA new drug approvals per year).

As the largest clinical program in North America and with our new location on this dedicated research and innovation campus in Washington, D.C., Children’s National and the RDI are uniquely poised to dramatically change the field of rare disease medicine. Our clinical models have started spreading to other centers across the country and will help shape the field for years to come. We are evolving rare disease into a true mainstream medical field, and the ability to make this type of change to a field is very unique to Children’s National.

Learn more about the Children’s National Research & Innovation Campus.

sick child in palliative care hospital bed

Children’s National Research Institute receives NIH grant for palliative care study

sick child in palliative care hospital bed

A new NIH grant will support the first study that examines palliative care needs in pediatric rare disease community.

The National Institute of Health (NIH) has awarded $500,875 to the Children’s National Research Institute (CNRI), the academic arm of Children’s National Hospital, to support a new study examining the palliative care needs of children living with rare genetic diseases.

This is the first study of families of children with genetic and metabolic conditions, termed collectively as rare diseases, that is designed to intervene to support the well-being of family caregivers and create advance care plans for future medical decision making. In the United States, a rare disease is defined as a particular condition affecting fewer than 200,000 people. Pediatric patients with rare diseases experience high mortality rates, with 30 percent not living to see their fifth birthday.

“Children with ultra-rare or complex rare disorders are routinely excluded from research studies because of their conditions, creating a significant health disparity. Surveys show that families of children with rare diseases are adversely impacted by lack of easy access to peer and psychological support,” says Maureen Lyon, Ph.D., Clinical Health Psychologist and Professor of Pediatrics at the CNRI and principal investigator on the project. “This study will examine the palliative care needs of family caregivers of children with rare genetic disorders and advance care planning intervention, which will ultimately help facilitate discussions about future medical care choices that families are likely to be asked to make for their child.”

Although greatly needed, there are few empirically validated interventions to address these issues Currently, there is only one intervention described for families of children with rare diseases — a Swedish residential, competence program — which focuses on active coping. However, this intervention does not address pediatric advance care planning, a critical aspect of palliative care.

Lyon adds that the major benefit of this proposed project will be filling the gap in knowledge about what family caregivers of medically fragile children with rare diseases want with respect to palliative care. In the United States, these families are expected to provide a level of care that, until a few decades ago, was reserved for hospitals.

Maureen E Lyon

Maureen Lyon, Ph.D., Clinical Health Psychologist and Professor of Pediatrics at the CNRI and principal investigator on the project.

“Our hope is that this study will provide a structured model for facilitating family decisions about end-of-life care, for those families who do not have the good fortune to have children who have the capacity to share in decision-making,” Lyon says.

In addition to bridging the knowledge gap regarding palliative care in rare disease patients, the study will also help inform current clinical, ethical and policy discussions, as well as the legal issues in a variety of areas, such as the debate surrounding advocacy, particularly for those children with impairments in physical function.

“We look forward to the results of this study,” said Marshall Summar, M.D., director of the Rare Disease Institute and division chief, Genetics and Metabolism at Children’s National Hospital. “As a leader in rare disease care, we continually examine how we can improve care and support for our patient families at our clinic and want to share our findings with others engaged in caring for rare disease patients. Because rare diseases can be life limiting in some cases, we need to learn all we can about how best to care and support a patient and family as they prepare for a potential transition to palliative care.”

All research at Children’s National Hospital is conducted through the CNRI, including translational, clinical and community studies. The CNRI also oversees the educational activities and academic affairs of the hospital and the Department of Pediatrics at the George Washington University School of Medicine and Health Sciences, frequently partnering with many other research institutions regionally and nationally. CNRI conducts and promotes translational and clinical medical research and education programs within Children’s National Hospital that lead to improved understanding, prevention, treatment and care of childhood diseases.

Jana and Stephen Monaco

Prenatal screening: the story of two siblings

Alex and Stephen Monaco

Stephen Monaco with his brother before a life-changing incident in 2001.

Jana and Tom Monaco have four children and two, Stephen and Caroline, were born with isovaleric acidemia (IVA) and secondary carnitine deficiency, a rare metabolic disorder. This genetic condition prevents the body from producing enzymes to break down the amino acid leucine, found in many proteins – from nuts and beans to chicken and fish. If undetected, the condition, which affects about one in 250,000 children, can be fatal. IVA can also lead to autism or severe brain damage. Fortunately, newborn screenings in every state now detect most IVA cases.

Eighteen years ago, a series of events happened with Stephen, age 3.5 at the time, which led to his diagnosis of having IVA and secondary carnitine deficiency. He celebrated his grandmother’s birthday with a family dinner on Memorial Day. The next day he woke up with symptoms of a stomach virus, which the family treated as such. The following morning he didn’t wake up at all. Jana went to his room to check on him and realized something was wrong. She called an ambulance and within 24 hours Stephen fell into a coma in her arms. He was immediately put on life support at a Virginia hospital.

Amy Lewanda, M.D., a geneticist, and Craig Futterman, M.D., an intensivist, both of whom now work at Children’s National Health System, delivered news about the condition: IVA is an inability for the IVD gene to create enzymes to break down protein. Within a 24- to 48-hour period, Stephen’s body flooded with isovaleric acid it couldn’t break down. Once the acid reached his brain he was paralyzed. Jana mentions you could find him in the emergency department of the hospital by following the odor: He reeked of ketones and isovaleric acid, which accumulated in his blood and body tissue. His blood glucose level was so low that he was practically in a diabetic coma.

Jana and Stephen Monaco

Jana and Stephen Monaco, at a charity golf tournament established in Stephen’s honor to raise awareness about and support for isovaleric acidemia (IVA).

If the Monaco family was able to get his blood checked locally at the hospital – which the clinicians did not yet have the ability to do because this condition is so rare – they may have been able to receive an early diagnosis, enabling them to intervene in infancy, as they did with their youngest daughter, Caroline.

After the diagnosis, in hindsight, Jana and Tom recognized Stephen’s symptoms as a toddler: picky eating, anemia, rejection of protein-rich foods, such as favoring jelly over peanut butter on a PB&J sandwich, opting for easy carbs, since they are easier for those with IVA to process, and breastfeeding longer, since breast milk is lower in protein. He had a peculiar odor trailing from his diaper, a common symptom of this condition. They also remembered he had a harder time recovering from a stomach virus, which left him weak and floppy, compared to one of his brothers, who had the same flu but bounced back faster. As parents, they did everything they could to promote healthy growth and development for their children – from properly installing  car seats to staying up-to-date on vaccines and enrolling everyone in activities, like Little League. They only wished they could have detected this condition earlier.

A second chance arrived six months after Stephen was diagnosed with IVA: Jana and Tom learned they were pregnant with Caroline. From studying Stephen’s condition, they knew Caroline had a 25 percent chance of having IVA and secondary carnitine deficiency. (Jana and Tom are recessive carriers for a mutated IVD gene, but remain asymptomatic.) They scheduled an amniocentesis, a prenatal test that provides information about a baby’s health from sample amniotic fluid, which can diagnose genetic defects and fetal infections. Caroline was just 16 weeks in utero, but abnormal metabolites from the amniotic fluid sample confirmed she had IVA and secondary carnitine deficiency.

Caroline Monaco

Caroline, a healthy teenager with IVA, is an example of the benefits of newborn screenings and early-life medical interventions.

Having advance knowledge about the condition enabled doctors and geneticists to create a plan for her delivery, which made a difference between her long-term prognosis and Stephen’s. After birth, she was transferred to the neonatal intensive care unit at Children’s National. She was fed a formula that prevented excess isovaleric acid build-up, part of an hour-by-hour protocol to ensure she stayed healthy. Caroline is now 16. She plays the viola in her school orchestra, rides horses and excels in school.

When Stephen was born, the state of Virginia, where the Monaco family lives, screened for eight prenatal conditions, such as PKU, a rare but more common condition. The state now screens for 31 conditions, thanks in part to Jana, Stephen and Caroline. The list grows as research evolves. Jana started advocating for these efforts in Richmond and on Capitol Hill when Caroline was 2. Her approach: Take Stephen and Caroline to her state capitol and to the U.S. Capitol to push for statewide newborn screenings – visually showing the same condition, but with two very different outcomes. How could anyone say no?

She worked with the Virginia Genetics Advisory Council and with the Health and Human Services Secretary Advisory Committee to pass the legislation, which helped detect other organic acidemias – inherited conditions that prevent babies from breaking down amino acids found in protein, creating potentially toxic situations, similar to Stephen’s. They advocated for adding other conditions to the panel, like severe combined immunodeficiency, commonly referred to as “bubble boy” syndrome. Stephan was the only newborn screening advocate in attendance with a disability. Now all 50 states have implemented these screenings.

Attendees of the charity golf event

The Monaco family raised $100,000 for the genetics division and ongoing IVA research at Children’s National Health System.

The family isn’t done yet. On Oct. 26, Stephen will celebrate his 22nd birthday and a fifth-annual golf tournament, created in his honor, to raise awareness about and support for IVA and similar conditions. The Monaco family started this tradition in 2015 on Stephen’s 18th birthday and have raised $100,000 for the genetics division at Children’s National. They hope Stephen’s legacy will leave others with a message they keep framed in their Virginia home: Learn from yesterday, live for today and hope for tomorrow.

They educate Caroline along the way, noting the annual golf tournament and their advocacy supports ongoing IVA research and care – ensuring that she and others with these rare metabolic conditions continue to live a long, healthy life, echoing their longstanding partnership with Children’s National to help children grow up stronger.