Lethal white foal syndrome (OLWS) is a lethal hereditary disease of horses with the frame overo pattern, described in Paint, Quarter Horse and Appaloosa. Homozygous foals are born white or nearly white and present intestinal aganglionosis (absence of enteric ganglia), the equine equivalent of Hirschsprung's disease. The colon does not function, the foal develops ileus and obstructive colic within the first 24-48 hours and dies or must be euthanized. Heterozygotes are healthy and display the frame overo coat pattern, so DNA testing is the only way to breed overo coats safely.

Described in Paint horse, Quarter Horse, Appaloosa and crosses with overo coat. Carrier frequency depends entirely on coat lines: appreciable in frame overo populations and practically nil in non-overo lines (limited data outside North America). Systematic testing of overo breeding stock keeps it under control.

- White or nearly white foal at birth, apparently normal initially\n- Absence of meconium passage and failure to defecate\n- Progressive colic and abdominal distension within the first 24-48 hours\n- Nasal reflux and signs of complete intestinal obstruction\n- Rapid deterioration with no response to medical or surgical treatment\n- Death or humane euthanasia within the first days

White foals that died with obstructive colic within the first hours were repeatedly described in North American stock breeds during the 1970s and 1980s. In the late 1990s, association studies identified the responsible gene: the endothelin receptor B (EDNRB), the same one involved in human Hirschsprung's disease and in the spotted coat of rodents. Characterization of the mutation made it possible to develop the carrier test, now routine in Paint and overo-coated breeds. OLWS thus became a classic example of a coat gene with a lethal effect in double dose.

- Test every breeding animal with overo coat or overo ancestry, even if its markings are minimal\n- Never breed carrier with carrier: 25% risk of lethal white foals in each foaling\n- A carrier can be bred with a free individual: half the offspring will be overo and you can select allele-free offspring\n- Do not assume from the coat: tobiano or sabino patterns are not due to the OLWS allele; only the test clarifies it\n- Record results and monitor lines with a history of white foals dying in the first days

In a white foal with early obstructive colic, the differential diagnosis includes atresia of the colon or ileum, meconium retention, peritonitis and bladder rupture; the classic picture in a foal of overo parents is OLWS until proven otherwise and the prognosis is nil, with humane euthanasia recommended. Genetic confirmation of the foal and testing of both parents are essential for breeding advice. Remember that frame expression can be minimal in carriers (hidden or cryptic frame).

1. Santschi EM, Vrotsos PD, Purdy AK, Mickelson JR. 1998. Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses (Mamm Genome) (PMID 9530628).
2. Metallinos DL, Bowling AT, 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 (Mamm Genome) (PMID 9585428).
3. Santschi EM, Vrotsos PD, Purdy AK, Mickelson JR. 2001. Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome in white-patterned horses (Am J Vet Res) (PMID 11197568).
4. OMIA:000629-9796 (Megacolon / OLWS, EDNRB, Equus caballus).