Lethal White Syndrome

Lethal white syndrome is a condition of foals born with a deadly genetic defect - one that is linked with the white pattern so coveted by breeders. Although the defect is linked to the white pattern, not all horses with white carry the gene that is responsible for the symptoms of lethal white syndrome.

Story originally posted by: Michael Lowder, DVM, MS The University of Georgia

This defect is the result of a mutation in the gene sequence in the overo phenotype. Research has identified the mutation as the Lys118 allele (a pair of genes position on the same site on paired chromosomes, containing specific inheritable characteristics) that is inexplicitly joined to the early formation of the lower gastrointestinal tract in the fetus.

When two white patterned horses carrying the gene (heterozygous carriers) are bred, there is a 25% chance that the foal will be conceived with a copy of the mutation from each parent, making him homozygous for the condition. Unfortunately, a foal carrying both copies will exhibit the symptoms of lethal white syndrome.

These foals are usually born totally white, although a small spot of dark color may be apparent. More importantly, these unfortunate babies arrive with an incomplete lower colon because nerve cells in the lower portion of their gastrointestinal tract do not develop. This makes it impossible to pass the first meconium.

The consequences of their genetic make-up are not fully recognized until birth. Signs of colic are often followed by death within the first twenty-four hours. There is no treatment for lethal white syndrome, and euthanasia is the only recourse. It should be noted, however, that not all white foals are lethal white foals. Clinical signs and veterinary evaluation is paramount to determining status.

Lethal white foals are usually produced when an overo mare is bred to an overo stallion, but can also occur with crosses with tobiano and others with overo ancestry. Overo is a broad category which includes frame, calico, splashed and sabino types, and is characterized by broad white pattern reaching from the abdomen up to the middle of the back. The white does not cross the back, and is often extensive on the head.

Studies show that frame overos, highly white calico overos, and frame blend overos have the highest incidence of producing lethal white foals. Although many believe that all overos contain the mutation, research indicates that there are a small percentage of overo-patterned horses that do not carry the gene for lethal white syndrome. This is why certain stallions and mares never throw a lethal foal. The absence of the mutated gene in some overos indicates that the white pattern, itself, may be regulated by more than one gene.

Because the gene that causes lethal white has been identified, one can now test the status of breeding horses and decrease the odds of a lethal white foal. This DNA-based diagnostic test can be run on blood and hair with follicles attached, and the information obtained can give you a better understanding of the odds.

The odds of producing a lethal white foal may cause confusion for some. Why, you ask, if breeding an overo to an overo gives you a 25% chance of a lethal white foal, don’t you see statistics verifying this percentage?

There are several reasons. First of all, not all overos carry the gene – only by breeding two overos with the mutation will you have a 25% chance of a lethal white foal. Secondly, all lethal white foal deaths are most likely not reported; It’s difficult to obtain statistics of lethal white births. Finally, the incidence of lethal white is a gamble.

Roll a dice six times and see how many times you actually roll a three. Statistics would say that one roll out of every six rolls would land you a three, but this does not necessarily happen. Each time you breed two horses with the defective gene, you have a one in four chance of a lethal white foal. Sometimes you’re just unlucky.

A recent study involving 945 white-patterned and 55 solid-colored horses presented for DNA identification of the lethal white gene (Lys118 allele) revealed that 73% of overos and overo blends in the study had the mutation. Frame and frame blend overos had the highest incidence of occurrence with 96% positive for the lethal gene, while 100% of loud calicos (all 37 loud calicos represented in the study) contained the mutation.

White patterns with the lowest incidence of Lys118 allele included splashed white overo, sabino, minimal white calico overo, nonframe blend overo, tobiano and breeding stock solid. Breeding stock horses of the American Paint Horse lineage always have some white markings, and the incidence of the lethal white gene in this particular study ran 18% (26 horses out of 146 tested).

Without knowing the genetic make-up, the best means of improving your odds in avoiding lethal white is to cross an overo with a solid or tobiano. The incidence of the Lys118 allele is much lower in tobianos (10%, or 11 out of 109 horses tested in the study carried the gene), and those with the greatest risk have overo lineage in their ancestry.

Solid-colored (without any white) horses appear to not carry the mutation, which is directly related to white coat pattern, so one can drastically reduce the odds of conceiving a lethal white and still have a 50% chance of obtaining an overo foal by breeding an overo to a solid.

While the thought of conceiving of lethal white foal may be worrisome, the actual percentage of foals born with this condition is relatively low. With the aid of DNA testing, you can selectively breed with confidence. A beautiful colored foal is a sight to behold.