Megaoesophagus (German Shepherd)

Gene: MCHR2

Transmission: Autosomal, sex influenced

Mutation: Deletion, MCHR2 gene; deletion of 33 nt VNTR sequence within intron 1 of MCHR2

Medical system: Digestive

Breeds: German Shepherd

Age of onset of symptoms: By 4 weeks, after weening.

Megaoesophagus is a relatively common congenital anomalie seen in dogs that can have both genetic and environmental causes.  It involves dilation of the esophagus with disrupted peristalsis and poor functioning of the esophageal sphincter resulting in chronic regurgitation of food, difficulty swallowing, increased salivation, marked weight loss, stunted growth and aspiration pneumonia.  The prognosis for survival in affected animals is poor.  Megaoesophagus has been described in a number of dog breeds, including the Shar-Pei, Dachshund, Great Dane, Labrador Retriever,Miniature Schnauzer, Newfoundland, Parson Russell Terrier, Springer Spaniel and German Shepherd.  Only for the German Shepherd has a gene mutation been associated with the disease.  For the German Shepherd, genetic studies identified the deletion of a variable number tandom repeat (VNTR) element within intron 1 of the MCHR2 gene, which codes for the MCHR2 (Melanin-Concentrating Hormone Receptor 2) protein.  This protein has a known function in controlling appetite and gastro-intestinal motility.  The VNTR element contains a T-box binding motif, suggesting that it is involved in regulating MCHR2 protein expression.  Normally, dogs and wolves have two copies of this repeat; German Shepherd dogs that are homozygous for only one copy of the repeat are at particular risk of developing megaoesophagus.  Interestingly, male puppies are twice as likely as female puppies to develop megaoesophagus, suggesting a possible protective function of estrogen in female animals.  DNA tests are now available to identify carriers of the one copy repeat such that this problematic allele can eventually be eliminated from the breed and the incidence of the disease reduced.

References:

OMIA links: [0631-9615], [2716-9615]

Bell SM, Evans JM, Evans KM, et al (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 Genet 18(3):e1010044.  [pubmed/35271580]

Haines JM. (2019) Survey of owners on population characteristics, diagnosis, and environmental, health, and disease associations in dogs with megaesophagus. Res Vet Sci 123:1-6.  [pubmed/30543946]

Mace S, Shelton GD, Eddlestone S. (2012) Megaesophagus. Compend Contin Educ Vet 34:E1.  [pubmed/22488663]

Tsai KL, Noorai RE, Starr-Moss AN, et al. (2012) Genome-wide association studies for multiple diseases of the German Shepherd Dog. Mamm Genome 23:203-11. [pubmed/22105877]

Contributed by: Sarah Lidam and Julianne Leclair, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).