On February 27, 2020, in the Price Center/Block Research Pavilion’s LeFrak Auditorium, the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (IDDRC) hosted its eighth annual celebration of Rare Disease Day, an event commemorated in over 100 countries. The auditorium was filled to overflowing as more than 150 members of the Einstein community, joined by individuals with rare disease and their families, came to participate in the special symposium, “Precision Medicine Meets Rare Disease: The Family-Clinician-Scientist Partnership.”

The unique event exemplified the Einstein Montefiore mission to bring science to the heart of medicine by highlighting successful partnerships between patients’ families, clinicians, and scientists. Attendees learned of the moving clinical odysseys experienced by the Forsman, Celiberti and Robl families—whose children suffer from mutations in MAN2B1, DYNC1H1 and KDM5C genes, respectively. Remote viewing via Zoom was set up to accommodate the enthusiastic interest in these presentations.

To begin the symposium, Dr. Steven Walkley, director of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK IDDRC) introduced the afternoon’s program by reminding those in attendance why it is so important for the Einstein and Montefiore community to celebrate Rare Disease Day. He cited contributions made throughout the College of Medicine’s 65-year history toward understanding and treating rare diseases.

Before introducing the families who would share their intimate experiences with rare disease, Dr. Walkley invited neurodevelopmental pediatrician Dr. Lisa Shulman, professor of pediatrics and interim director of Montefiore’s Rose F. Kennedy  Children’s Evaluation and Rehabilitation Center (CERC), to speak about what she and her CERC team had learned during a morning session held with 12 families whose children have difficulties with cognition, learning, socializing, and behavior resulting from KDM5C mutations.

Interviews Reveal Personal Journeys

In the first of three interviews conducted during the program, Dr. Robert Marion, chief of the genetics division (pediatrics) at Montefiore and professor of pediatrics and of obstetrics & gynecology and women’s health at Einstein, spoke with Danielle and Jeff Forsman, along with their 20-year old daughter Sarah. They shared how a bone marrow transplant that Sarah received at age 4 corrected her rare and often fatal brain disease, alpha-mannosidosis, caused by a MAN2B1 gene mutation.

“Hearing how Sarah’s rare brain disease had been corrected early in her life was a true inspiration to everyone present,” recalled Dr. Sophie Molholm, associate director of the IDDRC. “It reinforced the overriding message of the day that ‘Science matters.’”

Equally inspiring and remarkable is that 10 years prior to Sarah’s successful transplant in 2004, Dr. Walkley’s laboratory at Einstein published pioneering studies that established the efficacy of the approach used to treat her particular lysosomal disease. The researcher only learned of Sarah’s successful life-changing treatment last year, when she and her father introduced themselves to him at an international lysosomal disease meeting.

An Inside Peek at Translational Research

Next, Dr. Melissa Wasserstein, chief of pediatric genetic medicine at Montefiore and professor of pediatrics and of genetics at Einstein, spoke with Lindsay and Tom Celiberti, and their son Tyler. The Celibertis shared Tyler’s experiences with a mutation in DYNC1H1, a gene controlling production of a key motor protein in cells, which results in a complex neurodevelopmental disorder.

They were joined by Dr. Arne Gennerich, associate professor of anatomy and structural biology, who explained how his lab is investigating the particular protein that is affected in DNYC1H1, including a version of the protein that his team has modified to mirror the gene mutation affecting Tyler.

Reflecting on her family’s experience, Lindsay Celiberti told the organizers, “…we are eternally grateful for the opportunity to bring the issues surrounding the impact [of] DYNC1H1 on our family to life. It took until the event was over for me to recognize how profound and unique it is to have researchers, doctors and families all together in one room, all hoping and fighting for the same outcome. What a spectacular gift. It was a day we will truly never forget.”

A Rarity Within Rare Disease

In the afternoon’s final interview, Hayden Hatch—an M.D./Ph.D. candidate whose doctoral work in Dr. Julie Secombe’s lab focuses on how mutations in KDM5C affects brain development and behavior—spoke with Amy and Chris Robl and their daughters Gabby and Ashley about their experience with KDM5C, which is especially rare among girls. Hayden was instrumental in bringing the Robl family to Einstein for Rare Disease Day, which in turn spurred nearly a dozen other KDM5C families to also come to Einstein for the day’s events. Prior to Rare Disease Day, the group—which included a family that traveled from England—had only “met” on Facebook.

Hayden noted, “Gabby was thrilled to meet another girl who had the same condition as her. The two became instant best friends and continue to keep in touch. Their meeting exemplifies how knowing you’re not alone in a predicament can give one hope and be empowering.”

All three families were applauded for their bravery in sharing their struggles and triumphs by an appreciative audience of Einstein researchers and students. And everyone was reminded that “Alone we are rare, but together we are strong.”

Foundation for Supporting Progress

The separate morning program that brought together the families whose children have mutations of the KDM5C gene offered them the opportunity to learn more about their children’s condition and also how to start a foundation—an essential for garnering support to conduct funded research into the disorder. During the session, the Foglio family, whose son Ben has Salla disease, offered insights from their experience establishing the S.T.A.R. Foundation for Salla Disease after taking part in Rare Disease Day at Einstein in 2018.

“The idea for the morning session was conceived of and executed by Einstein student Hayden Hatch, who is a member of Julie Secombe’s lab,” said Dr. Walkley, director of the IDDRC. “It offered a truly unique opportunity for these families, who can often feel as if they and their loved ones are suffering alone. To know there are others out there, and to see how you can come together to garner support from clinicians and scientists, is empowering and uplifting.”

He noted that the special program was further enhanced through major collaboration with and support from Dr. Lisa Shulman and her colleagues at RFK CERC. Upon learning that a dozen families whose children had mutations in the same gene would be coming to Einstein’s Rare Disease Day, the CERC specialists created a questionnaire aimed at learning more about the characteristics of each child affected by this ultra-rare disorder.

They sent the survey to the families to complete in advance, and also posted it to the KDM5C Facebook Support Group page two weeks prior to the event. The CERC team then compiled data based on the responses they received and presented them to the families during the morning session. A panel of specialists also were on hand to answer questions parents had about their children’s conditions.

The survey has remained accessible on the group’s Facebook page, with more than 30 responses received to date.

To know there are others out there, and to see how you can come together to garner support from clinicians and scientists, is empowering and uplifting.

Steven Walkley, D.V.M., Ph.D.

A production team headed by Areeg Sweis and Nicholas Kovacic filmed the group during both the morning and afternoon programs. Footage from these shoots will be included in a documentary, titled “Rare,” which stems from the Foglio family experience. The goal of the film is to raise awareness of rare disease and share the journey of families working with scientists and clinicians to identify potential treatments for Salla disease, which is characterized by early physical impairment and intellectual disability.

Following the event, Jessica Klein-Foglio had a message for the IDDRC researchers. She wrote: “I just want to thank you for today. Thank you for giving a purpose for our lives. Thank you for helping us find our Salla group...who has truly become family… Thank you for the hard work you pour into the lives of so many who struggle with rare disease. I love the IDDRC and what this is doing for families like ours.”

Spotlight on Rare Diseases

The National Institutes of Health currently recognizes 7,000 rare diseases, with 250 new ones added to the list annually; these disorders and diseases often impact only a handful of individuals. The annual worldwide Rare Disease Day, typically is held on February 29 or the closest day to it, since it’s a rare day on the calendar. It was created to shed light on the numerous rare conditions there are, as well as the remarkable individuals who experience them and the journey they undertake with their families.

Following the IDDRC Rare Disease Day symposium, a reception along Einstein’s Main Street featured an exhibit of nearly three dozen research posters, illuminating ongoing efforts in Einstein laboratories and Montefiore clinics that are focused on rare diseases. The festivities were further enlivened by the entertaining music performed by Musicians of Einstein, also known as MoE.

“Each year, we focus on a different aspect of rare disease and also look to highlight research going on at Einstein and Montefiore that is seeking insights into these debilitating, often life-threatening disorders,” said Dr. Molholm. “It was thrilling to see the interest and enthusiasm at this year’s event and to be able to showcase the efforts of so many labs.”