General Description

Lethal white overo (also known as frame overo) is a variant of the EDNRB gene that produces a white spotting pattern. Lethal white overo is an example of incomplete dominance, as horses that inherit one copy have a different phenotype than horses with two copies. Heterozygous horses (LWO/n) tend to have patches of white bordered (“framed”) by normal pigmentation, usually with blue eyes. In the typical expression, white patterning generally does not cross the topline. Homozygous horses (LWO/LWO) are born completely white and with megacolon, which necessitates immediate euthanasia on humane grounds.

Some heterozygous horses do not have an obvious white spotting pattern, but still can produce lethal white foals. Crossing two LWO/n horses has a 25% chance of producing LWO/LWO. Thus, it’s recommended to test even solid horses prior to breeding if there is any chance they could carry lethal white overo.

Genotype and Phenotype

LWO/n = Carrier; one allele detected, "Overo" or "Frame Overo". No known ill affect beyond white markings, possible blue eye(s). Can pass one LWO allele to 50% of any offspring. LWO/LWO = Affected; Horse may be aborted, stillborn or born white with incomplete digestive tract resulting in death. n/n or negative = Non-carrier, non-affected; unable to pass LWO to any offspring.

-Spotting patterns generally follow after the color of the pigmented regions, for example “bay frame overo” or “palomino frame overo.” -In some breeds, horses with at least one tobiano allele and any overo pattern are called “tovero.” -Horses with multiple spotting variants can be born completely white and healthy. White foals out of frame overo mares without clinical signs of megacolon should undergo genetic testing.

Gene Information

EDNRB is a G-protein coupled receptor that is vital for normal development. Mutations in both the horse and in other species have led to white spotting and lack of nerves in the digestive tract. The LWO mutation is a dinucleotide substitution that results in an amino acid change and thus alteration of the encoded protein.

References

Santschi EM et al., “Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.” (1998) Mamm Genome. 9: 306-9.

Metallinos DL et al., “A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease.” (1998) Mamm Genome. 9: 426-31.

Yang GC et al., “A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.” (1998) Hum Mol Genet. 7: 1047-52.

Santschi EM et al., “Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome in white-patterned horses.” (2001) Am J Vet Res. 62: 97-103.

Lightbody T, “Foal with Overo lethal white syndrome born to a registered quarter horse mare.” (2002) Can Vet J. 43: 715-7.