Lethal White Overo (LWO) | Veterinary Genetics Laboratory (2024)

Lethal white overo (LWO) is a hom*ozygous; lethal condition associated with the frame overo white spottingpattern. 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 thepigmented 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 causedetermined 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 gene endothelin 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 veryminimal white spotting patternhave 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 beenassociated 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.

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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