Lethal white overo (LWO) is a genetic disorder that results from two copies of the version of the gene causing the frame overo coat color pattern.
Phenotype: Lethal white overo (LWO) is a genetic disorder that results from two copies of the version of the gene causing the frame overo coat color pattern. Foals with the condition are characterized by a completely white coat as well as intestinal tract abnormalities that result in death soon after birth. The frame overo pattern itself is characterized by a white spotting pattern in which pigment is said to "frame" the horse.
Horses with N/N genotype will not have the overo pattern and cannot transmit this lethal white overo variant to their offspring.
Horses with N/O genotype will have the overo pattern. They may transmit this lethal white overo variant to their offspring. Matings with N/N horses will result in a 50% chance of producing an overo foal. Matings with N/O horses will result in a 25% chance of producing a lethal white foal.
Horses with O/O genotype will have LWO, a condition incompatible with life.
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Lethal white overo (LWO) is a homozygous; lethal condition associated with the frame overo white spotting pattern. The frame overo pattern, like all other white spotting patterns, can vary along a continuum from a horse with very minimal white to a horse with lots of white. This particular pattern was named after horses from in the middle of the range upwards, that is the pigmented area is said to “frame in the horse” and thus white patterning primary occurs on the abdomen, middle of the neck, and on the face.
Foals born with the lethal white overo syndrome are affected by intestinal tract abnormalities, leading to colic and eventual death. Horse breeding programs specializing in the frame overo pattern have particular challenges compared with programs for other white patterns such as tobiano. When breeding two horses with the frame pattern, not only is there the possibility of producing a solid dark foal without the overo pattern, but there is also the risk of producing an all-white foal that dies of complications from intestinal tract abnormalities (ileocolonic aganglionosis).
This was the first white spotting pattern to have the genetic cause determined in horses and was discovered at the Veterinary Genetics Laboratory. The mutation responsible for the LWO condition is a two base pair mutation (p.Ile118Lys) in the geneendothelin B receptor gene (EDNRB). EDNRB is responsible for the proper development of both pigment cells and nerve cells during embryogenesis. Mutations in this same gene cause a similar disease in humans known as Hirschsprung disease. Horses with two copies of the mutation (O/O) have the lethal condition as there is no treatment. These foals usually die shortly after birth. Horses with one copy of mutation (N/O) have a frame overo pattern but do not have any known intestinal complications but maybe deaf.
Breeders can test horses for the identified mutation to avoid producing lethal white foals. Some horses with a very minimal white spotting pattern have one copy of the LWO allele (O) and can also therefore produce affected foals. Matings between two N/O horses will results in a 25% chance of producing an LWO affected foal. Therefore, testing for LWO is important to assist veterinarians to make the correct diagnosis and to assist owners in management and breeding decisions.
We know of no other mutations that have been associated with lethal white frame overo horses. However, owners requesting the diagnostic test should understand that there is the rare possibility that two NN horses could have a lethal white foal if both the sire and dam carry a mutation at a site other than the one detected by this test.
No copies of the lethal white overo variant detected.
1 copy of the lethal white overo variant detected.
2 copies of the lethal white overo variant detected.
Metallinos, D. I., Bowling, A. T., Rine, J. (1998). A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: An equine version of Hirschsprung Disease. Mammalian Genome, 9(6), 426-431. doi: 10.1007/s003359900790
Lightbody, T. (2002). Foal with Overo lethal white syndrome born to a registered quarter horse mare. The Canadian Veterinary Journal, 43(9), 715-717. PMID: 12240532
Magdesian, K.G., Williams, D.C., Aleman, M., Lecouteur, R.A., & Madigan, J.E. (2009). Evaluation of deafness in American Paint Horses by phenotype, brainstem auditory-evoked responses, and endothelin receptor B genotype. Journal of the American Veterinary Medical Association, 235(10), 1204-1211. doi: 10.2460/javma.235.10.1204