Overo Lethal White Syndrome (OLWS) is a condition that occurs in newborn foals. The condition is genetic, caused by a recessive gene, and both parents must carry a copy of the gene for a foal to be born with this defect. Horses that carry this gene are most commonly overo white patterned horses (frame overos), but there are exceptions. The defective gene has been found in American Paint Horses, American Miniature Horses, Half-Arabians, Thoroughbreds, and horses formerly called cropout Quarter Horses (foals born to registered Quarter Horse parents that have too much white to qualify for registration with the American Quarter Horse Association. This rule was removed from the AQHA at the 2004 Convention). The mating of two horses carrying the recessive gene will statistically result in a 25% chance of a lethal white foal.

OLWS foals have blue eyes and are completely or almost completely white at birth. These foals initially appear normal except for their unusual coloring. After a varying period of time, signs of colic will emerge due to the foal's inability to pass feces. The OLWS foal has an underdeveloped, contracted intestine caused by a failure of the embryonic cells that form nerves in the gastrointestinal system. These cells also play a role in determining skin color. There is no treatment for OLWS, and surgery to bypass the intestinal damage has never been successful due to the extensive nature of this type of lesion. Veterinarians advise euthanasia for all OLWS foals because death will inevitably occur from colic caused by fatal constipation.

OLWS is emotionally injurious and often financially devastating for small breeders because it is always fatal. The best way to ensure you will never lose a foal to OLWS is to have your mare(s) and stallion tested prior to breeding and never breed two carriers.

Using clues from other species, researchers at the University of Minnesota investigated the same genes in OLWS foals, and found a mutation. A test for the defective allele (each gene is made of two alleles, one inherited from each parent) was quickly developed. Testing of OLWS foals, their parents, and unrelated horses revealed that all OLWS foals had two copies of the defective gene, each of their parents had one, and unrelated horses had none. Simply put, if carriers are never again bred to each other, there can never be another OLWS foal born. Horses at greatest risk of carrying the defective allele are overos, particularly of American Paint Horses and American Miniature Horse breeding. A small number of Tobiano and breeding stock horses also carry the defective gene, and a very small number of carrier horses have been detected in other breeds. These other carriers include Pinto horses, which indicates that as other breeds import overo color patterning, they can also import the lethal gene.                                
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