Megaesophagus (CIM) in German Shepherds

Megaesophagus is a serious esophageal motility disorder in which the esophagus loses its ability to move food and liquids into the stomach. Food accumulates in the esophagus, causing it to dilate, or it can be passively returned (regurgitated) back into the mouth. Possible aspiration of food into the lungs can lead to pneumonia.

The disease is caused by a change in the number of repeats in a so-called T-box motif in the MCHR2 gene. A T-box is a short section of DNA that normally has a certain number of repeats. The change in the number of repeats is associated with an impact on the function of the gene. While healthy dogs and wolves have two copies of the repeats, in the case of CIM we encounter only a single copy of the repeat. The disease develops only in homozygous individuals (alleles with one copy of the repeat must be inherited from both parents).

The disease is twice as common in males, probably due to endogenous female factors (e.g., estrogen) that promote relaxation of the sphincter between the esophagus and stomach, facilitating the passage of food.

References:

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.