young girl holding baby doll

Loeys-Dietz Syndrome and Inflammatory Bowel Disease

CDHF

Written by: CDHF

Updated: November 16th, 2022

What is Loeys-Dietz Syndrome?

Loeys-Dietz syndrome (LDS) is a rare genetic disorder that affects the connective tissue in the body. The disorder was first described in 2005 by Dr. Bart Loeys and Dr. Hal Dietz at the Johns Hopkins University School of Medicine.

LDS is caused by a mutation (change) in either the TGFBR1 or TGFBR2 genes (transforming growth factor beta receptor 1 or 2), the SMAD2 or SMAD3 genes (mothers against decapentaplegic homolog 2 or 3), or the TGFB2 or TGFB3 genes (transforming growth factor beta 2 or 3).

There are six genetic causes of Loeys-Dietz syndrome:

  1. Loeys-Dietz syndrome type 1, caused by mutations in the TGFBR1 gene
  2. Loeys-Dietz syndrome type 2, caused by mutations in the TGFBR2 gene
  3. Loeys-Dietz syndrome type 3, caused by mutations in the SMAD3 gene
  4. Loeys-Dietz syndrome type 4, caused by mutations in the TGFB2 gene
  5. Loeys-Dietz syndrome type 5, caused by mutations in the TGFB3 gene
  6. Loeys-Dietz syndrome type 6, caused by mutations in the SMAD2 gene

Loeys-Dietz syndrome is a genetic disorder. The genetic component means that LDS is present in an individual since their conception and that LDS may be passed from parent to child in an autosomal dominant inheritance pattern. This pattern means that each offspring of an individual with LDS has a 50% chance of inheriting the gene mutation for LDS and the condition. There is no way to predict the severity of symptoms that may occur.

Individuals with LDS exhibit a variety of medical features in the cardiovascular, musculoskeletal, cutaneous (skin), immune, and gastrointestinal systems. LDS medical characteristics will vary from person to person, with various combinations of features ranging from mild to severe in presentation.

Four common features of LDS include:

It’s important to note that that these findings are not observed in all patients and do not concretely lead to a diagnosis of LDS. It is recommended that you consult your physician or a local geneticist if you have questions about individual health concerns.

For a detailed list of symptoms, visit the Loeys-Dietz Syndrome Foundation Canada’s website.

Individuals with LDS are more likely than the general population to experience gastrointestinal issues including eosinophilic esophagitis and gastritis or inflammatory bowel disease.

What is Inflammatory Bowel Disease (IBD)?

Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of the digestive tract, and is the umbrella term for two, separate disorders that cause inflammation (redness and swelling) and ulceration (sores) of the small and large intestines. These two disorders are called ulcerative colitis and Crohn’s disease. IBD has an enormous impact on affected people, and Canada has one of the highest rates of IBD in the world. IBD can be painful and debilitating and may even lead to life-threatening complications.1

Ulcerative colitis symptoms include:

Crohn’s disease can range from mild to severe. It can develop gradually or come on suddenly, without warning. Symptoms, which vary widely depending on the location of the disease along the digestive tract, may include:2

How is Loeys-Dietz syndrome related to gastrointestinal issues and IBD?

People with Loeys-Dietz syndrome (LDS) often develop gastrointestinal issues, including food allergies, eosinophilic gastrointestinal disease (eosinophilic esophagitis, gastritis, and colitis), constipation, and inflammatory bowel disease (ulcerative colitis and Crohn’s disease). 3 

Compared to the general population, individuals with LDS are more likely to have a food allergy to peanuts, tree nuts, milk, soy, eggs, shellfish, fish, wheat, or other foods. Symptoms of a food allergy may be mild, such as swollen, flushed skin or stomach discomfort and bloating, or more severe, such as hives, uncontrollable cough or wheezing, difficulty breathing, vomiting, diarrhea, severe cramping, dizziness, fainting, or blue fingertips or lips. To diagnose a food allergy, a doctor may use a skin-prick test, blood test, or food elimination diet.

Eosinophilic gastrointestinal disease (EGID) is an inflammation of the gastrointestinal tract, from the esophagus (eosinophilic esophagitis), to the stomach and small intestine (eosinophilic gastritis), to the large intestine (eosinophilic colitis).8 This inflammation can be caused by food allergies. In this case, the gastrointestinal tract contains a greater than normal amount of eosinophils, a type of white blood cell involved in the body’s response to infections and allergies. 8 EGID symptoms include vomiting, diarrhea, nausea, food stuck in the esophagus, trouble swallowing, weightloss, and severe heartburn. A diagnosis can be made through a biopsy of the gastrointestinal tract.4

When it comes to inflammatory bowel disease (IBD), it is estimated that 4.3% of people with LDS have IBD.6 While further studies are needed among larger groups of people, preliminary research shows that people with LDS may be more likely than others to develop IBD and that the genetic mutations of LDS types 1 and 2 may be involved in its development.

Management of Gastrointestinal Issues, including IBD

Gastrointestinal concerns, such as IBD, EGID, and issues related to food allergies, may affect people for their whole lives. To reduce the frequency and severity of symptoms, proper management is important and must be tailored to each individual. CDHF and LDSFC recommend working closely with your gastroenterologist and other doctors to come up with a treatment and management plan that works for you. The plan may include medication, dietary changes, the use of a feeding tube, or surgery.

To manage LDS gastrointestinal concerns, it is recommended to7:

Table: Guidelines for Gastroenterology and Nutrition

Source: MacCarrick, G.; Black III, J. H.; Bowdin, S.; El-Hamamsy, I.; Frischmeyer-Guerrerio, P. A.; Guerrerio, A. L.; Sponseller, P. D.; Loeys, B.; & Dietz, H. C. (2014). Loeys-Dietz syndrome: A primer for diagnosis and management. Genetics in Medicine, 16(8), pp. 576 – 587. DOI: https://doi.org/10.1038/gim.2014.11

To learn more about Loeys-Dietz syndrome, visit the Loeys-Dietz Syndrome Foundation Canada’s web site at https://www.loeysdietzcanada.org.

Learn more about Crohn’s Disease.

Learn more about ulcerative colitis. 


References

  1. Coenen S et al. Eur J Gastroenterol Hepatol 2017;29:646.
  2. Chauhan U et al. J Can Assoc Gastroenterol 2022;5:129.
  3. MacCarrick, G.; Black III, J. H.; Bowdin, S.; El-Hamamsy, I.; Frischmeyer-Guerrerio, P. A.; Guerrerio, A. L.; Sponseller, P. D.; Loeys, B.; & Dietz, H. C. (2014). Loeys-Dietz syndrome: A primer for diagnosis and management. Genetics in Medicine, 16(8), pp. 576 – 587. DOI: https://doi.org/10.1038/gim.2014.11
  4. Loeys-Dietz Syndrome: Gastrointestinal issues. Loeys-Dietz Syndrome Foundation. (n.d.). Retrieved October 17, 2022, from https://loeysdietzcanada.org/assets/web/documents/fact_sheets/2019/en/LDSF%20US_Gastrointestinal%20Issues%20Fact%20Sheet_Dec%204%202019.pdf
  5. Naviglio, S.; Arrigo, S.; Martelossi, S.; Villanacci, V.; Tommasini, A.; Loganes, C.; Fabretto, A.; Vignola, S.; Lonardi, S.; & Ventura, A. (2014). Severe inflammatory bowel disease associated with congenital alteration of transforming growth factor beta signaling. Journal of Crohn’s and Colitis, 8(8), pp. 770 – 774. DOI: https://doi.org/10.1016/j.crohns.2014.01.013
  6. Guerrerio, A. L.; Frischmeyer-Guerrerio, P. A.; Huang, C.; Wu, Y.; Haritunians, T.; McGovern, D. P. B.; MacCarrick, G. L., Brant, S. R.; & Dietz, H. C. (2016). Increased prevalence of inflammatory bowel disease in patients with mutations in genes encoding the receptor subunits for TGFB. Inflammatory Bowel Disease, 22(9), pp. 2058 – 2062. DOI: https://doi.org/10.1097/MIB.0000000000000872
  7. MacCarrick, G.; Black III, J. H.; Bowdin, S.; El-Hamamsy, I.; Frischmeyer-Guerrerio, P. A.; Guerrerio, A. L.; Sponseller, P. D.; Loeys, B.; & Dietz, H. C. (2014). Loeys-Dietz syndrome: A primer for diagnosis and management. Genetics in Medicine, 16(8), pp. 576 – 587. DOI: https://doi.org/10.1038/gim.2014.11
  8. Eosinophilic gastrointestinal disease. Gastrointestinal Society. (2022, August 9). Retrieved October 5, 2022, from https://badgut.org/information-centre/a-z-digestive-topics/eosinophilic-gastrointestinal-disease/

Related Articles:

View all News & Articles

Test tubes of a drug

Switching from a Biologic to a Biosimilar Drug in Canada

Online dietitian consult

What is the Equity in Nutrition Care Program?

Doctor speaking to teenager in office

Transitioning from Pediatric to Adult IBD

Parent shaking hands with doctor with teenager in the background

IBD Transition Checklist for Patients and Parents

young girl holding baby doll

Loeys-Dietz Syndrome and Inflammatory Bowel Disease

Toilet paper with smiley face

Is my Poop Healthy/Normal?

IBD Nurses Report on an Ipad

IBD Nurse-Centred Care Impact Report

CDHF Talks with Dr. Yvette and the CDHF talks logo

CDHF Talks: Understanding the Benefits & Risks of IBD Treatment Options

Mediaplanet: Living with IBD: An Invisible Illness

Children in a classroom raising their hands to answer a question

Blackboards and Bathrooms: A comprehensive resource to help teachers support the education of children with IBD

Women sitting in robe

Spa Day? No thanks, I have a Colonoscopy.

Functional Foods with Added Probiotics

Women and male bathroom stall

Managing your Digestive Health in the Workplace Webinar

Hands on top of other hands supporting one another

IBS, IBD & Mental Health Webinar

Tornado over someones stomach, holding stomach

Living with Ulcerative Colitis Infographic

Stethoscope on blue background

IBD Treatment Options: Understanding Your Risks and Benefits

Robbie’s Rainbow “You, Me and IBD” Magazine

Stethascope on a blue background

Transition Pathway Brochure for IBD Patients

IBD Awareness Month

November is IBD Awareness Month

People sitting on a computer listening to a presentation

Hot off the Presses: The Latest IBD Information from Scientific Meetings Webinar

Webinar: Understanding the Benefits and Risks of IBD Therapies

Preparing for your GI Appointment

Registered dietitian writing in notebook on desk

My Experience with Crohn’s Disease as a RD

Two young boys playing hockey

Pediatric Inflammatory Bowel Disease: Dr. Thomas Walters

Inflammatory Bowel Disease (IBD) with Dr. Mike Evans

IBD Treatment Options- Understanding Your Benefits and Risks Animation

IBD and Pregnancy

CDHF Talks: Dietary Updates and Recommendations for the IBD Patient on a Biosimilar

Uncovering Biologics: Your IBD Bodyguard!

Ulcerative Colitis and Crohn’s Disease: What’s the Difference? Infographic

Fecal Calprotectin: The Inside Story on Inflammation

Teenager sitting outside with headphones on

Living with Crohn’s Disease: Infographic

Taking a photo of food

Diet & Lifestyle Changes for Inflammatory Bowel Disease (IBD)

CDHF Talks: Managing Inflammatory Bowel Disease (IBD) in the Elderly

CDHF Talks: Maintaining a Healthy Weight with IBD

IBD Animation

Switching from a Biologic to a Biosimilar

Teen boy talking to doctor

Biosimilars for IBD: Making the Transition Webinar

Woman in chair reading her laptop and smiling

Biosimilar Library

CDHF Talks: Your New Infusion Clinic

Girl watching ipad

Inflammatory Bowel Disease Digital Toolkit for the Newly Diagnosed

My Life with Ulcerative Colitis

The Timeline of my Ulcerative Colitis Diagnosis

What I Eat in a Day with Ulcerative Colitis

Ulcerative Colitis: My Day to Day with IBD

Let’s Imagine UC Differently

Living Positively with Ulcerative Colitis

Photo of David Mcguire

My First Surgery for Crohn’s Disease: My Life Changed Forever

Man lifting a weight in the gym

5 Sure-Fire Ways to get Bigger, Stronger and Leaner while having IBD: Crohn’s Disease

Notebook with Crohn's disease written on it

Right Hemicolectomy: My Experiences. What’s Next?

Medication on a blue microbe background

IBD Medications during COVID-19

Christmas present

Navigating the Holidays with Inflammatory Bowel Disease (IBD)

Women looking off to the side

Setting Goals to Manage IBD

COVID-19 Vaccines in Immunocompromised Patients with Inflammatory Bowel Disease (IBD)

Covid vaccine

Should IBD patients take the COVID-19 vaccine?

Kids running outside with pool floaties on vacation

The Facts on Diarrhea when Travelling

Toilet paper rolling out with a purple background

Why is there Blood in my Stool? Rectal Bleeding

Bear on hospital bed with child

Children with IBD: A Shift in Hospitalization Rates

Yogurt bowl

Inflammatory Bowel Disease and Dietary Patterns

Women looking off to the side with her cell phone in hand

Behaviour Change Strategies

Fecal calprotectin stool test

What is the Fecal Calprotectin Test?

healthy foods

Diet & Lifestyle Changes for Inflammatory Bowel Disease (IBD)

David in the gym looking off to the side

The Psychological effects of IBD: My Crohn’s Story and how I Overcame It

Teenager with his mother

Transitioning from Pediatric to Adult IBD Webinar