OMIA:000631-9615 : Megaoesophagus in Canis lupus familiaris

In other species: domestic cat , sheep , domestic ferret , llama , goat , cattle , horse

Categories: Digestive / alimentary phene

Links to MONDO diseases: No links.

Mendelian trait/disorder: no

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Cross-species summary: Dilatation and atony of the body of the oesophagus, usually associated with asynchronous function of the oesophagus and the caudal oesophageal sphincter. Causes regurgitation and aspiration pneumonia.

Mapping: By conducting a GWAS on 19 affected and 177 control German Shepherd dogs, each genotyped with the Affymetrix v2 canine SNP chip (Yielding 48,415 SNPs for the analysis), Tsai et al. (2012) highlighted a 4.7Mb region on chromosome CFA12.

Bell et al. (2022) also highlighted a region in CFA12: "A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility." It is not evident whether this region overlaps the region highlighted by Tsai et al. (2012).

Molecular basis: Bell et al. (2022): "Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM [Congenital idiopathic megaesophagus] (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM.

Prevalence: Bell et al. (2022) reported "that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage".

Control: Bell et al. (2020): "Together, sex and the MCHR2 repeat sequence accurately predict affection status in over 75% of dogs, and a genetic test is now available to facilitate breeding decisions aimed at reducing disease incidence."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MCHR2 melanin-concentrating hormone receptor 2 Canis lupus familiaris 12 NC_051816.1 (58932320..58907909) MCHR2 Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1437 German Shepherd Dog Congenital idiopathic megaesophagus MCHR2 repeat variation Naturally occurring variant CanFam3.1 12 Bell et al. (2022): "Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk". 2022 35271580


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2022 Bell, S.M., Evans, J.M., Evans, K.M., Tsai, K.L., Noorai, R.E., Famula, T.R., Holle, D.M., Clark, L.A. :
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 Genet 18:e1010044, 2022. Pubmed reference: 35271580 . DOI: 10.1371/journal.pgen.1010044.
2016 Manning, K., Birkenheuer, A.J., Briley, J., Montgomery, S.A., Harris, J., Vanone, S.L., Gookin, J.L. :
Intermittent at-home suctioning of esophageal content for prevention of recurrent aspiration pneumonia in 4 dogs with megaesophagus. J Vet Intern Med 30:1715-1719, 2016. Pubmed reference: 27481487 . DOI: 10.1111/jvim.14527.
2012 Mace, S., Shelton, G.D., Eddlestone, S. :
Megaesophagus. Compend Contin Educ Vet 34:E1, 2012. Pubmed reference: 22488663 .
Tsai, K.L., Noorai, R.E., Starr-Moss, A.N., Quignon, P., Rinz, C.J., Ostrander, E.A., Steiner, J.M., Murphy, K.E., Clark, L.A. :
Genome-wide association studies for multiple diseases of the German Shepherd Dog. Mamm Genome 23:203-11, 2012. Pubmed reference: 22105877 . DOI: 10.1007/s00335-011-9376-9.
2002 Watrous, B.J., Blumenfeld, B. :
Congenital megaesophagus with hypertrophic osteopathy in a 6-year-old dog Veterinary Radiology & Ultrasound 43:545-549, 2002. Pubmed reference: 12502108 .
2001 Hopper, K., Beck, C., Slocombe, R. :
Megaoesophagus in adult dogs secondary to Australian tiger snake envenomation Australian Veterinary Journal 79:672-675, 2001. Pubmed reference: 11712704 .
Huber, E., Armbrust, W., Forster, J.L., Ribiere, T., Grosclaude, P. :
Megaoesophagus in the dog: a case report Schweizer Archiv fur Tierheilkunde 143:512-514, 2001. Pubmed reference: 11680912 .
2000 Torres, P. :
Esophagus-diaphragmatic Cardioplasty for the treatment of the idiopathic congenital total megaesophagus in dogs [Spanish] Archivos de Medicina Veterinaria 32:121-130, 2000.
1999 Plotnick, A.N. :
Megaesophagus and hypothyroidism in an English Springer Spaniel and response to thyroxine supplementation Canine Practice 24:14-17, 1999.
Rossmeisl, J.H., Blevins, W.E., Widmer, W.R. :
What is your diagnosis? Diagnosis - Radiographic diagnosis - Megaesophagus and gastrointestinal atony Journal of the American Veterinary Medical Association 215:782-+, 1999. Pubmed reference: 10496127 .
1997 Borbe, J., Walla, L. :
Surgical and postoperative management of canine megaesophagus [German] Kleintierpraxis 42:329-332, 1997.
Gaynor, A.R., Shofer, F.S., Washabau, R.J. :
Risk factors for acquired megaesophagus in dogs Journal of the American Veterinary Medical Association 211:1406 ff., 1997.
Mears, E.A., Jenkins, C.C. :
Canine and feline megaesophagus Compendium on Continuing Education for the Practicing Veterinarian 19:313 ff., 1997.
Torres, P. :
Megaesophagus in the dog - a bibliographic review and a new classification proposal [Review] [Spanish] Archivos de Medicina Veterinaria 29:13-23, 1997.
1996 Holland, C.T., Satchell, P.M., Farrow, B.R.H. :
Vagal esophagomotor nerve function and esophageal motor performance in dogs with congenital idiopathic megaesophagus American Journal of Veterinary Research 57:906-913, 1996. Pubmed reference: 8725822 .
1995 Whitley, N.T. :
Megaoesophagus and glucocorticoid-deficient hypoadrenocorticism in a dog Journal of Small Animal Practice 36:132-135, 1995. Pubmed reference: 7783439 .
1994 Holland, C.T., Shelton, G.D., Satchell, P.M., Farrow, B.R.H. :
Antibodies to Nicotinic Acetylcholine Receptors in Dogs with Megaoesophagus Australian Veterinary Journal 71:221-222, 1994. Pubmed reference: 7945104 .
Matros, L., Jergens, A.E., Miles, K.G., Kluge, J.P. :
Megaesophagus and Hypomotility Associated with Esophageal Leiomyoma in a Dog Journal of the American Animal Hospital Association 30:15-19, 1994.
Thilagar, S., Balasubramanian, N.N., David, W.P.A., Sasikala, S. :
A Clinical Survey of Megaesophagus in the Dog Indian Veterinary Journal 71:921-922, 1994.
1993 Holland, C.T., Satchell, P.M., Farrow, B.R.H. :
Oesophageal Compliance in Naturally Occurring Canine Megaoesophagus Australian Veterinary Journal 70:414-420, 1993. Pubmed reference: 8280024 .
Holland, C.T., Satchell, P.M. :
Megaoesophagus in the Dog and Cat Recueil de Medecine Veterinaire 169:969-983, 1993.
1990 Knowles, K.E., Obrien, D.P., Amann, J.F. :
Congenital Idiopathic Megaesophagus in a Litter of Chinese Shar-Peis - Clinical, Electrodiagnostic, and Pathological Findings Journal of the American Animal Hospital Association 26:313-318, 1990.
1957 Michael, S.J. :
Regurgitation in pups. II. Megaesophagus in a pup Journal of the American Veterinary Medical Association 130:284 only, 1957. Pubmed reference: 13416103 .

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 20 May 2013
  • Changed by Frank Nicholas on 13 Mar 2022