What is Familial Dysautonomia?
We celebrate the life of Helen’s cover girl, Sam Myers, who had FD and passed away in 2022.
By Lanie Etkind
Picture babies failing to thrive, a horrifying fatal prognosis, and distraught parents who would do anything for life-prolonging treatment and eventual cure. Seventy-five years ago, a caring pediatrician named Dr. Conrad Riley, who with his colleague, Dr. Richard Day, had recently identified a rare hereditary syndrome, Riley-Day Syndrome and later it renamed Familial Dysautonomia (FD). They brought together the first five families to form a support group, one of the first parent groups for a genetic disease in the United States. While its genetic origins were still unknown, the fact that all the families were of Ashkenazi Jewish descent suggested that this group was at risk. With strength in numbers, the parents could compare symptoms and explore and discuss treatments and care. In 1951, the small group of forward-thinking parents formed the Familial Dysautonomia (FD) Foundation.
Today, the FD Foundation works for the benefit of all people afflicted with FD, fewer than 800 ever diagnosed and only about 300 worldwide currently living with the disorder. We support medical care and scientific research, and conduct social service and public awareness programs. The Foundation continues to be the main source of funding for the Dysautonomia Treatment Center at NYU Langone in New York City, the only place in the US providing clinical care for people with FD, and the model for a sister center in Israel. The Foundation also funds research for treatments that improve life expectancy and quality of life for people with FDs.
“FD affects the autonomic and sensory nervous systems that are responsible for involuntary functions and occurs almost exclusively in people from Ashkenazi Jewish heritage. Symptoms present at birth include trouble swallowing, and inability to regulate blood pressure, heart rate, body temperature and breathing. ”
FD affects the autonomic and sensory nervous systems that are responsible for involuntary functions and occurs almost exclusively in people from Ashkenazi Jewish heritage. Symptoms present at birth include trouble swallowing, and inability to regulate blood pressure, heart rate, body temperature and breathing. Patients typically cannot produce tears and are insensitive to pain. They often experience severe autonomic crises, episodes of cyclical vomiting accompanied by extremely high blood pressure and increased heart rate, sweating and fever. When the Foundation was formed, diagnosis was based on symptoms and clinical testing. Treatment, then and now, focuses on managing symptoms through a variety of interventions.
In 1970, Dr. Felicia Axelrod established the Dysautonomia Treatment Center at NYU Medical Center, which she directed until retiring in 2015, when Dr. Horacio Kaufmann took over as Director. Dr. Alejandra Gonzalez-Duarte joined as Assistant Director in 2022 and is now Co-Director. Today, the Center follows about 175 patients and consults with doctors managing the care of those with FD in locations worldwide. A multidisciplinary team of highly trained physicians, nurse practitioners and researchers manages patient care, performs annual physicals, handles patient emergencies and oversees clinical research.
The work of Dr. Axelrod and now Dr. Kaufmann and Dr. Gonzalez-Duarte, has had a tremendous impact on prolonging lives. 75 years ago, half of the children born with FD did not survive past age five due to aspiration pneumonias caused by the inability to swallow properly. Due to substantially improved care developed by the Dysautonomia Center, today the largest number of adults are living with FD since the first diagnosis in 1949; today, a person with FD has a 75 percent chance of living to age 40. Unfortunately, FD is progressive and degenerative, so older FD patients face new symptoms such as failing vision, spin curvature, unstable gait and impaired balance and coordination.
In 1990, the Foundation board, in consultation with scientists, launched research to locate the gene responsible for FD and funded the prominent geneticist, Dr. James Gusella, of the Harvard School of Medicine. In 1991, Dr. Susan Slaugenhaupt joined Gusella’s lab, bringing a strong background in gene mapping, the process of locating genes on chromosomes.
With the Foundation’s support, in collaboration with the Treatment Center, and with funding from the NIH, in 2001, Dr. Slaugenhaupt discovered the FD gene mutation on Chromosome 9Q. The gene is inherited in an autosomal recessive manner, when both otherwise healthy carrier parents pass on their copy of a mutated gene to the fetus. Once the gene was located, potential parents could be tested to determine if they carried the gene. While the occurrence of FD in a baby is rare, approximately 1 in 30 Jews of eastern European ancestry are known to be carriers of the gene. The Foundation advocated for required screening for at-risk families through the American Academy of Obstetrics and Gynecology. FD was added to the Jewish Genetic Screening Panel and is now a routine part of all prenatal carrier screening, resulting in dramatically fewer FD births worldwide.
Dr. Slaugenhaupt and her team identified the mutation as a gene-splicing error in Elongator complex protein 1 (ELP1, also known as IKBKAP); since then, she has dedicated her work to discovering how to repair the splicing defect as a route to a therapeutic intervention for those with FD. In 2016, Dr. Slaugenhaupt’s lab generated a phenotypic mouse model (mice with FD) and in 2019 was able to successfully correct the splicing defect in her mice, a treatment that has the potential to improve patients’ sensory-motor coordination and intervene in the onset of spinal abnormalities.
The Foundation continues to work closely with international FD communities, including in Israel, where the second largest FD population resides. FD physicians and scientists in Israel are on the Foundation’s Scientific Advisory Board, Israeli families are invited to join educational programming where live Hebrew translation is offered, and the NYU Dysautonomia Center hosts international grand rounds enabling physicians caring for FD patients around the world to share their knowledge and experience.
The 2020s are an exciting time for the FD Foundation. The work of its international Scientific Advisory Board and its support for research has accelerated the search for treatments to slow or arrest FD’s degenerative effects. Researchers have been approaching FD from all angles; several potential treatments are currently in the pipeline, including gene therapy and small molecule drugs; an antisense oligonucleotide clinical trial was launched in 2024.
The Foundation spun off a for-profit Public Benefit Corporation called Tikun Therapeutics in 2024 to gain access to potential new funding sources to support these research endeavors. The NYU Treatment Center is committed to expanding access for patients through annual checkups via telemedicine (begun during the COVID-19 pandemic so that patients would not have to travel to New York) and will continue to build the FD natural history study, which is crucial for providing essential knowledge for research on rare diseases, while proceeding with exciting, groundbreaking treatments.
The FD Foundation, a small but mighty group, is on the cusp of developing several treatments that could be game-changing for our patient community. As the Foundation approaches our 75th anniversary in 2026, we are proud of all we have accomplished; with the support of our friends, and the good fortune of having many brilliant physicians and researchers on our team, we anticipate continued success in ensuring better and longer lives for those impacted by this ultra rare neurological disorder.
About the Author
Lanie Etkind is the Executive Director of Familial Dysautonomia Foundation, Inc. (www.familialdysautonomia.org)