Introduction
Congenital idiopathic megaesophagus (CIM) is an esophageal motility disorder present at birth. A normal esophagus contracts to allow the passage of food into the stomach but with CIM the esophagus does not contract normally, so food stays in the esophagus and stretches it. Affected puppies regurgitate food and water, cough, can be poor-doers, and are at risk for pneumonia when regurgitated food particles are breathed into the lungs. There is no known treatment for the disorder, but affected puppies are managed with small, frequent meals fed while the dog sits in an upright position, thus allowing gravity to help food move into the stomach. The medication sildenafil has also shown promise in helping treat this disease.
Key Points
- CIM is a serious esophageal disorder that causes puppies to regurgitate food and risk pneumonia.
- German Shepherd Dogs are most commonly affected, especially males.
- A genetic mutation combined with sex can predict CIM risk with 75% accuracy.
- A new genetic test helps breeders plan matings to reduce disease incidence.
- Sildenafil shows promise as a supportive treatment for affected dogs.
Challenge Background
CIM has no known cure, and management typically involves feeding dogs upright and in small, frequent meals. German Shepherd Dogs are disproportionately affected, and until recently, the cause was largely unknown.
This lack of understanding made it difficult for breeders and veterinarians to predict which dogs might be affected, leaving owners to manage symptoms without knowing why their puppies were sick. CIM can severely impact a dog’s quality of life, with frequent regurgitation leading to poor nutrition and a high risk of aspiration pneumonia. Because symptoms often appear early in life, affected puppies may struggle to thrive, and can be poor-doers.
The Breakthrough
A Clemson University research team, funded by the AKC Canine Health Foundation, has identified specific genetic variations associated with CIM in German Shepherd Dogs (02709: Identification of Genetic Risk Factors Contributing to Gastrointestinal Motility Disorders). These variations occur in a gene that codes for a signaling molecule involved in appetite, weight regulation, and gastrointestinal motility.
The breakthrough lies in the discovery that a combination of genetic mutation and sex can predict a dog’s risk of developing CIM with 75% accuracy. Male dogs are twice as likely to be affected, possibly due to estrogen’s protective role in females. This finding has led to the development of a genetic test that allows breeders to assess risk before mating, helping reduce the number of affected puppies.
Training the Next Generation of Canine Health Researchers
Dr. Sarah M. Bell was awarded an AKC Canine Health Foundation Clinician-Scientist Fellowship in 2019 and 2020, sponsored by the Orthopedic Foundation for Animals (OFA). She earned a Bachelor of Science degree in genetics from Clemson University and has continued there as a graduate research assistant pursuing a doctoral degree in genetics. Under the mentorship of CHF-funded investigator Dr. Leigh Anne Clark, Dr. Bell has been studying the genetic basis of congenital idiopathic megaesophagus (CIM) in German Shepherd Dogs and Great Danes. The goal of her study is to develop a genomic prediction tool to help breeders plan matings that will not produce dogs with CIM without sacrificing genetic diversity.
Impact & Next Steps
This breakthrough offers a powerful tool for breeders to reduce the incidence of CIM in German Shepherd Dogs through informed mating decisions. The genetic test developed from this research allows for early identification of at-risk dogs, improving both prevention and long-term care strategies.
CHF-funded investigators are continuing their work, performing genetic analysis in Great Danes. Data is also being examined from dogs with gastric dilatation-volvulus (GDV or bloat), another motility disorder seen in large-breed dogs, to see if there are any shared genetic risk factors between these two conditions. Ultimately, the goal is to understand the genetics that underlie these disorders allowing us to define an individual dog’s risk of disease and to help decrease the number of affected dogs.
Reference:
Bell, S. M., Evans, J. M., Evans, K. M., Tsai, K. L., Noorai, R. E., Famula, T. R., Holle, D. M., & Clark, L. A. (2022). Congenital idiopathic megaesophagus in the German shepherd dog is a sex-differentiated trait and is associated with an intronic variable number tandem repeat in Melanin-Concentrating Hormone Receptor 2. PLOS Genetics, 18(3), e1010044. https://doi.org/10.1371/journal.pgen.1010044
