By Charlene N. Rivera-Bonet | Waisman Science Writer
Down syndrome is a genetic condition in which all cells in a person’s body have an extra copy of chromosome 21, also known as trisomy 21. Having this extra chromosome affects how an individual’s body and brain develops. Approximately one in 772 babies in the United States are born with Down syndrome, according to the Centers for Disease Control and Prevention (CDC).
As recently as 1983, the life expectancy of a person with Down syndrome was 25 years. Better access to and improvements in care has increased the life expectancy significantly to 60. As the Down syndrome population grows older, their needs throughout the life course have become apparent, and both physicians and scientists work to better understand and meet these needs.
Down syndrome is a key focus of the Waisman Center’s research, service, training, and outreach activities. With a clinic solely dedicated to providing care to children with Down syndrome and their families, numerous research labs that work to better understand the condition and develop novel interventions, and resources and educational programs, the Waisman Center is a hub of holistic care and new developments for the care of individuals with Down syndrome and their families.
The Down Syndrome Clinic at the Waisman Center provides comprehensive care to individuals with Down syndrome. The specialized team of clinicians is one of the largest in the United States focused on Down syndrome. The team includes an occupational therapist, a physical therapist, a speech-language pathologist, a nurse, a registered dietitian, an audiologist, a social worker, a psychologist, and a developmental pediatrician. This broad range of expertise allows for attention to many of the health issues a person with Down syndrome might encounter. “We are so lucky to have the breadth and depth of knowledge that we have on our team,” says Amy Lyle, MSSW, social worker and clinic coordinator at the Down Syndrome Clinic.
Ultimately, the clinic aims to partner with patients and their families to support individuals with Down syndrome to meet their full potential developmentally, to live the healthiest and happiest lives possible, and to facilitate appropriate supports and inclusion in their schools and communities. “Our priority in the Down Syndrome Clinic, and all Waisman Center clinics, is family-centered care,” Lyle says. Maria Stanley, MD, a developmental behavioral pediatrician, directs the clinic. In addition to seeing patients, Stanley also does research focused on the patient population that she serves. One of her research focuses is assessing medications related to mental health or behavioral concerns in Down syndrome. “Clinicians see that children with Down syndrome often respond differently to medications, the dosing seems to be different and sometimes they are more sensitive to medication side effects,” Stanley says. “We need to understand what are the things that are the same for all children and what things are really unique.”
The structure of the Waisman Center encourages collaboration and crosstalk between the clinics and researchers. Just like the comprehensive clinical care, the research on Down syndrome, current and past, is interdisciplinary and broad. “What’s special about this place is the really wonderful interchange between the people who are primarily researchers and the folks who are primarily clinicians informing one another’s work,” Stanley says.
Family and lifespan research
Family inclusion is a critical aspect of care in the clinics, and is also a major focus of research for Marsha Mailick, PhD, emeritus vice chancellor for research and graduate education and former director of the Waisman Center, due to the major role that family plays in the life of an individual with Down syndrome. “The family context is critical. Very important for any developmental disability, because people grow up within a family. But Down syndrome is linked in complex ways with both risk and resilience in the family context,” Mailick says.
One of Mailick’s studies is a 20-year follow-up of an original cohort of individuals with Down syndrome. This study was conducted with former post-doc, Anna Esbensen, PhD, now professor of pediatrics at the Cincinnati Children’s Hospital. “We analyzed the data from how the adults were doing 20 years later, going all the way back to how the family was doing 20 years earlier, and what changed in between,” Mailick says.
Mailick’s team found that parents’ mental health had long-term effects on their son or daughter with Down syndrome. Better parental mental health lead to better functional abilities, better health, fewer behavior problems, and less risk of dementia in individuals with Down syndrome, emphasizing the importance of family context for healthy aging in adults with Down syndrome.
Aging and Alzheimer’s in Down Syndrome
As the lifespan of individuals with Down syndrome increases thanks to the advancements in medicine and research, it is crucial to investigate, as Mailick’s study did, what happens as they age. Several other Waisman studies are investigating aging in Down syndrome and the risk for developing Alzheimer’s disease.
Brad Christian, PhD, professor of medical physics and psychiatry, and Sigan Hartley, PhD, professor and 100 Women Distinguished Chair in Human Ecology, co-lead a study called Alzheimer Biomarkers Consortium of Down Syndrome (ABC-DS) that aims to better understand the course of Alzheimer’s disease in people with Down syndrome and to identify cognitive measures that are sensitive to detecting early declines. “The overarching goal of the research is to inform intervention trials that could delay or prevent Alzheimer’s in individuals with Down syndrome,” Hartley says.
In addition, the Hartley lab also studies how lifestyle factors such as sleep, physical activity, social engagement and cognitive stimulation may serve as risk or resiliency factors to delay the timing of Alzheimer’s disease in individuals with Down syndrome. In other words, while individuals with Down syndrome may also share a genetic risk for Alzheimer’s disease due to having three copies of chromosome 21, some individuals develop the disease much earlier than others. “This difference in the timing of when brain changes and cognitive declines occur may be related to differences in lifestyles, things that could be modified by interactions,” Hartley says.
Communication in Down syndrome
Communication is also affected in individuals with Down. This has been a big focus of research since the beginnings of Waisman. Researchers have made important strides in better understanding language processes as well as developing interventions to improve communication.
Robin Chapman, PhD, emeritus professor of communication sciences and disorders, and Jon Miller, PhD, CCC-SLP, emeritus professor of communication sciences and disorders, developed software called SALT (Systematic Analysis of Language Transcripts) that standardizes the process of eliciting, transcribing, and analyzing language samples, which they both used to better understand speech and language in individuals with Down syndrome.
Miller established comprehensive studies of early vocabulary development in children with Down syndrome. He also co-authored a book in 1999 on improving the communication of people with Down syndrome which provided a framework for assessing and treating speech, language, and communication problems in children and adults with the condition.
Chapman carried out research on language learning in children and adolescents with Down syndrome. One of her studies provided new evidence that in individuals with Down syndrome, language skills continue to develop into adulthood, contrary to the previous belief that it plateaued during childhood.
The lab of Audra Sterling, PhD, associate professor of communication sciences and disorders, views communication as a basic human right. The goal of her lab is to understand communication in individuals with Down syndrome and help them communicate in the ways they want to. In her research, Sterling seeks to understand the relationship between challenges in communication and co-occurring intellectual disability.
A significant part of Sterling’s research is including parents in the process of language acquisition. “I always like to think that the parents are the experts on their kids. They know how their kids communicate. They know their wants and needs,” Sterling says. So, her lab partners with parents and uses their expertise, but also teaches them new strategies to help facilitate language development.
Individuals with Down syndrome also have a higher incidence of hearing loss than typically developing children or adults. “The anatomy of the ear in people with Down syndrome is a little different,” explains Ruth Litovsky, PhD, professor of communication sciences and disorders and surgery, division of otolaryngology. They are more likely to have ear infections that can be conducive to hearing loss. Having hearing loss can also impact language, communication, and cognition, which people with Down syndrome are already at-risk for delays in. “Our novel research questions focus on whether individuals with Down syndrome with hearing loss would be even more likely to have higher risk for hearing difficulties, and whether those are associated with greater risk for delayed cognition and language,” says Litovsky.
In a study done in collaboration with Hartley, Litovsky’s group found that in young adults with Down syndrome, having hearing loss meant being more likely to be worse at understanding speech, both in quiet and in noise, and more likely to have worse performance in standard measures of attention, working memory, and executive function.
With a new grant, this study has been expanded to include multiple collaborators with different areas of expertise. Andy Alexander, PhD, professor of medical physics and psychiatry, will be obtaining magnetic resonance imaging (MRI) measures of brain structures and looking specifically at areas of the brain involved in hearing. Sterling also brings her expertise in language sample to the study, while Carlos Benitez Barrera, PhD, assistant professor of communication sciences and disorders, is investigating brainstem and cortical activity as a measure of neural maturation in the auditory system using electroencephalography (EEG). “This is an ambitious and exciting project with many investigators bringing their expertise to address a timely and important question,” Litovsky says.
Brain development and intellectual disability
Anita Bhattacharyya, PhD, associate professor of cell and regenerative biology, uses human pluripotent stem cells that derived from individuals with Down syndrome to study the development of the brain. By turning these stem cells into brain cells, Bhattacharyya’s group is identifying ways that brain development is different in Down syndrome. The Bhattacharyya lab first developed these valuable trisomy 21 stem cells and they are used by researchers all over the world.
Collaborating with other researchers in the center including Su-Chun Zhang, MD, PhD, professor of neuroscience and neurology, Daifeng Wang, PhD, associate professor of biostatistics & medical informatics and computer sciences, and André Sousa, PhD, assistant professor of neuroscience, the team is exploring what is different during brain development of individuals with Down syndrome that lead to intellectual impairment, and how those differences arise. “We’re going to set down fundamental knowledge that everyone’s going to use in the Down syndrome field. I think what we’re doing is so fundamental, that it will help change the field,” Bhattacharyya says.
Spreading the knowledge
In addition to research and clinical care, the Waisman Center is dedicated to sharing knowledge about Down syndrome with the community. Once a year, the center holds a Day with the Experts in collaboration with the Down Syndrome Association of Wisconsin-South Central (DSAW), and GiGi’s Playhouse Madison to share knowledge about Down syndrome across the life course, from research to the latest standards of care. Experts also include a panel of individuals with Down syndrome and their family members sharing experiences, insights and information.
Although the Waisman Center has many experts in both clinical services and research on Down syndrome, it is the families that really make the center what it is. Many of the families that come through the Waisman Center stay connected for decades. “We have such wonderful families,” Hartley says. “I think the most rewarding thing for us is getting to know these families. We see these families for over a decade, and we get to see how these families evolve over time.”