Experts Discuss Unique Study Aiming to Help People with Down Syndrome and Chronic Constipation

Down syndrome, also known as trisomy 21, is caused by an extra copy of chromosome 21 and is the most common chromosomal abnormality in the population. Research shows individuals with Down syndrome often experience widespread immune dysregulation and inflammation that can lead to many different co-occurring conditions including issues in the gut. Many are diagnosed with several types of gastrointestinal (GI) motility issues such as celiac disease, irritable bowel syndrome and chronic constipation during their lifetime.

A study recruiting participants with Down syndrome and chronic constipation offers comprehensive, immediate care while also helping scientists learn more about the condition.

Leaders of the study, Jaime Belkind-Gerson, MD, MSc, pediatric gastroenterologist and director of the Neurogastroenterology and Motility Program at Children’s Hospital Colorado and Kelly Sullivan, PhD, assistant professor of pediatrics and leader of the Experimental Models Program at the Linda Crnic Institute for Down Syndrome, answer questions about this research opportunity and give insight into treatment options. Anyone interested in the study can reach out to the clinical team by email at htp@ucdenver.edu.

What is chronic constipation?

Dr. Belkind-Gerson: Clinically, we consider constipation to be if you feel that going to the bathroom is troublesome, painful or you are just not going enough. The normal ranges for healthy bowel movements are from three per week to three per day. That means that some people go 90 times per month and others go 12 times per month and that is all considered normal. If you’re not in pain or straining and going enough to feel fine, that is considered healthy. Most parents of patients or patients with constipation tell us they are straining, nothing is coming out, they’re having stooling accidents, etc. Then, we know it’s constipation. While constipation is considered chronic if it lasts two to three months, most patients with Down syndrome report experiencing it for years - if not for their entire lives.

Why are individuals with Down syndrome more susceptible to chronic constipation?

Dr. Belkind-Gerson: We think it is related to the “second brain” or “gut brain.” This is what we call the millions of neurons that live in the gastrointestinal (GI) tract. Humans have half a billion neurons in our intestines, but research has shown people with Down syndrome have fewer active neurons in their intestines. The chronic inflammation caused by the extra copy of chromosome 21 leads to neuron death throughout the body. It is also linked to why people with Down syndrome have an increased risk of Alzheimer’s at an early age.

What inspired you to develop this study?

Dr. Belkind-Gerson: We are not treating our patients with Down syndrome and GI motility disorders appropriately. They’re just being given laxatives to go to the bathroom instead of getting to the root of the problem. Our research team hopes to figure out not only why these disorders are so prevalent, but also why they get worse with age. We want to find the underlying problems to help patients now and better understand the condition to improve future treatments.

Dr. Sullivan: This has been in the works for years. We first looked at data from one of the largest Down syndrome biobanks in the world called the Crnic Institute Human Trisome Project (HTP) and saw that chronic constipation is reported by about 25% of those participants. This percentage is incredibly high, but we’ve discovered some physicians are seeing it in over 50% of patients with Down syndrome. We believe this is widespread in the community and underreported, because many people can treat the symptoms with over-the-counter laxatives.

What is needed from participants?

Dr. Sullivan: If a person is interested in taking part in the study, they will have an initial consultation with Dr. Belkind-Gerson and if needed with his team of pelvic physical therapists, occupational therapists and pediatric psychologists. Then, if they’re eligible and agree to participate, they will meet with one of our clinical coordinators to learn more about the research and consent to the study. We will take a blood draw, mouth swab and stool sample. The blood draw and mouth swab are done in office, but the stool sample can be done with a kit at home. If the physician prescribes an endoscopy, biopsies will be taken and used for the research. An endoscopy is a very short procedure, and the patient is under general anesthesia. Potential other tests include cognitive testing, but there are no procedures needed outside of their medically indicated course of treatment.

What are the current treatment options?

Dr. Belkind-Gerson: Most practitioners suggest oral laxatives such as Miralax to help the condition, but often this is not enough, and patients continue to experience symptoms. In the Neurogastroenterology Program we can offer added help and experts including pelvic physical therapy and biofeedback, occupational therapy, visits with a psychologist, motility testing and more.

How is this research opportunity unique?

Dr. Sullivan: Chronic constipation in people with Down syndrome is not being widely studied. Participants in our research receive direct, immediate care with a holistic treatment plan.

Dr. Belkind-Gerson: If you ask a lot of patients and their families about chronic constipation, they will tell you how much it negatively affects their quality of life, and this isn’t a temporary issue. It’s something that causes people pain and discomfort every day. With this research, we’re working to figure out why people with Down syndrome are more susceptible to chronic constipation and be able to prevent it or treat it earlier in life.

How do interested people sign up?

Dr. Sullivan: Anyone who is interested or wants to learn more can contact our research team at htp@ucdenver.edu. There is also more information about the study on our website.