Megaesophagus Research Update

When the Fenway Foundation began its megaesophagus research project in the fall of 2021, our goal was clear: identify the genetic cause of this devastating disorder in Friesian horses and ultimately develop a test that could help breeders make informed decisions.

We knew from the beginning that reaching that goal would require carefully diagnosed horses and a great deal of patience. What we did not yet fully appreciate was just how varied esophageal disease can be within the Friesian breed, or how important those differences would become to interpreting the genetics.

Over the past several years, the project has grown well beyond the original group of affected foals and their families. We have collected clinical records, diagnostic images, DNA samples, necropsy findings, and histopathology from Friesians of many different ages and with a wide range of esophageal abnormalities. That expanded information has given us a much clearer picture of the disease, while also raising important new questions that must be answered before a genetic finding can be turned into a reliable test.

Where the Genetic Research Stands

In late 2024 and early 2025, the genetic analysis produced our most promising result to date. Within the original study population, the genetic pattern was consistent across every affected foal in our study. After years of collecting cases, sequencing genomes, and narrowing thousands of possibilities, this was a very encouraging development. That finding has not been disproven.

However, a genetic association is not the same thing as a validated genetic test. Before a test can be offered to breeders, researchers must determine exactly which form of disease the genetic finding predicts, how consistently it predicts it, and whether the horses used to establish the association were classified correctly.

As we expanded our review beyond the original, tightly defined group of affected foals and controls in early 2025, we found that not every suspected case or horse in the broader Friesian population fits neatly into the same pattern. That does not necessarily mean the original result is incorrect. It may mean the finding is associated most strongly with a particular form of the disease, that additional genetic factors are involved, or that some horses currently grouped together under the term “megaesophagus” do not have exactly the same underlying disorder.

An additional question arose when one of the original control horses, which initially showed no clinical signs of disease or diagnostic findings consistent with megaesophagus, was later discovered to exhibit signs consistent with megaesophagus during necropsy. The horse had not been recognized as having clinical esophageal disease during life, and we do not yet know whether the finding represented a disease process, an unrelated or idiopathic finding, or a change that can occur in some older Friesians without causing symptoms.

Until that distinction is understood, we cannot know whether the finding changes the horse’s classification as a control, or whether it has any effect at all on the interpretation of the original genetic result.

This does not indicate that the research has failed. Instead, it has made it clear to us that we have reached a stage where the biological meaning of the genetic finding must be established with greater precision.

"Megaesophagus" May Not Be One Uniform Disorder

Megaesophagus is commonly understood to mean an enlarged or dilated esophagus that does not move feed, water, and saliva toward the stomach normally. Affected horses may experience repeated episodes of choke, coughing, nasal discharge containing feed or saliva, difficulty swallowing, weight loss, or aspiration pneumonia and a variety of other symptoms. Our case review has shown, however, that esophageal disease in Friesians is much more varied than the name suggests.

Some affected horses have obvious dilation involving part or much of the esophagus. Others have serious problems with motility or feed retention without dilation. Some have substantial muscular thickening in the lower esophagus, which can narrow the passageway and contribute to obstruction. Still others have microscopic evidence of muscle degeneration, fibrosis, and other damage. In some horses, more than one of these patterns occurs at different locations within the same esophagus.

We have also found examples of horses that showed esophageal dilation or retained feed during examinations performed while they were alive, but did not have an obviously dilated esophagus at necropsy. Conversely, a horse may have no recognized history of esophageal disease but still have significant esophageal abnormalities discovered after death.

These findings suggest that the term megaesophagus may describe the end result of more than one underlying biological process. They also help explain why some suspected cases do not fit the genetic pattern identified in the original group.

The detailed scientific questions surrounding these differences are discussed more fully in our recent podcast episode, which is linked with this article. For the broader Friesian community, the most important point is this: before we can determine what a genetic result means, we must be certain that we are comparing horses with the same form of disease.

Why Defining the Right Control Horses Matters

Genetic research depends on comparing affected horses with horses that are truly unaffected. If a horse with subtle or unrecognized esophageal disease is included in the control group, the genetic comparison becomes much more difficult to interpret.

At the beginning of the project, a control was generally an older Friesian with no known history of megaesophagus. As we learned more about the disease, it became clear that a lack of clinical symptoms was not always enough. Some problems may be subtle, intermittent, or mistaken for isolated episodes of choke.

Diagnostic examinations in living horses can provide valuable information, but they also have limitations. Endoscopy offers only a view of the esophagus under the conditions present during that particular examination. A barium swallow can provide information about swallowing and movement through the esophagus, but it is technically difficult to perform and interpret in a large adult horse. Neither examination can show microscopic changes within the esophageal tissue.

Necropsy gives us the opportunity to examine the full length of the esophagus and collect tissue for histology. Even then, a routine necropsy may not provide everything the study needs. Subtle abnormalities can be missed unless the esophagus is examined specifically for this research, sampled at several standardized locations, and evaluated microscopically, even in areas that appear normal.

For this reason, we have developed a much more rigorous standard for validating control horses. Senior Friesians approaching or exceeding 25 years of age are especially valuable because they have had many years in which clinical disease could have appeared. When one of these horses eventually dies or is euthanized for an unrelated reason, a study-specific necropsy can help us establish what the esophagus of an aged, clinically unaffected Friesian should look like.

These controls are essential not only for the genetic analysis work, but also for determining which muscular and microscopic findings truly represent disease.

The Current Phase of the Project

The project continues to involve our established research collaborators, including the University of Kentucky and Wageningen University. We are also bringing additional expertise into the next phase.

Equine internal medicine expertise will help us review the clinical histories, diagnostic findings, and disease patterns represented in the study. This will help determine whether the differences we see between horses are clinically and biologically meaningful before those groups are used for further genetic analysis.

Royal GD in the Netherlands provides the facilities needed to conduct standardized necropsies, collect tissue from specific anatomical locations, and prepare histology slides. We are also exploring additional pathology collaboration in Europe to help establish what normal and abnormal esophageal tissue should look like in Friesians of different ages.

The pathology review will examine multiple levels of the esophagus rather than concentrating only on a visibly dilated or thickened area. Researchers will evaluate which muscle type and layer are affected and look for changes such as muscular hypertrophy, degeneration, regeneration, fibrosis, collagen remodeling, and abnormalities involving the nerves and structures that coordinate esophageal movement. Samples will also be taken from the stomach and aorta of each horse to determine if there are similar tissue changes between horses with megaesophagus, gastroparesis, and aortic rupture.

This carefully structured work should help us determine whether we are seeing different stages of one disorder, distinct forms of disease, or overlapping processes that can occur in the same horse.

Once the clinical and microscopic patterns are better defined, the genetic data can be reevaluated using more precise groups. That is the step needed to determine what the original genetic finding represents and whether it can become part of a dependable test.

How Friesian Owners Can Help

Our progress now depends heavily on participation from the Friesian community. There are several important ways owners can contribute.

Owners of affected or suspected horses

Please contact us if your Friesian has been diagnosed with megaesophagus or has experienced signs that may indicate esophageal dysfunction. These may include repeated choking, difficulty swallowing, coughing or nasal discharge while eating, unexplained feed retention, or documented dilation or impaired motility.

We would like to enroll these horses, collect DNA samples, and review any available veterinary reports, endoscopy findings, barium swallow studies, images, or videos. Even if a horse’s diagnosis is uncertain, the information may help us determine whether additional evaluation would be useful.

Owners of senior Friesians

We especially need Friesians near or over 25 years of age that have no known history of esophageal disease. These horses may be able to participate as potential controls.

Participation can begin while the horse is still living with the collection of DNA and health-history information. If the horse later dies or is euthanized for an unrelated reason, a study-specific necropsy and histology can help determine whether the horse qualifies as a validated control.

Contacting us in advance is extremely important. The esophagus must be examined and sampled in specific locations, and some tissues must be handled in a particular way to remain useful for research.

Help us reach other owners

Even if you do not currently own an affected horse or a potential control horse, you can help by sharing this information. Veterinarians, breeders, and fellow owners may know of a horse that could make an important contribution to the study.

The Fenway Foundation reimburses the collection and shipping of research samples. We also reimburse study-related necropsy and histology expenses.

To discuss participation, contact us at info@fenwayfoundation.com

Every well-documented horse strengthens the study. An affected horse may help us understand the range of disease. A carefully validated senior control may help us distinguish normal aging from an inherited abnormality. A veterinary report, DNA sample, or properly collected tissue may provide the missing information needed to understand what the genetic findings mean.

The path toward a reliable genetic test has proven more complex than anyone initially hoped, but the project is also substantially stronger because of what we have learned. We are no longer looking only for a genetic difference. We are working to understand precisely which disease that genetic difference may cause, how that disease appears across a horse’s lifetime, and how to recognize horses that are truly unaffected.

That foundation is essential if the eventual result is to be scientifically sound, useful to breeders, and protective of the Friesian horse for generations to come.

For a more detailed update on our Friesian megaesophagus research, click the link below to listen to our podcast episode.

Megaesophagus Research Update