Overo Lethal White Foal Syndrome (OLWS)

Etiology & Pathophysiology

• OLWS (also known as ileocolonic aganglionosis) is caused by a missense mutation (Ile118Lys) in the endothelin receptor B (EDNRB) gene, essential for neural crest cell migration during embryogenesis. This mutation disrupts development of both enteric ganglia and melanocytes, producing characteristic clinical signs.

• The result is aganglionosis of distal small intestine and colon, leading to colonic ileus, megacolon, and ultimately fatal functional intestinal obstruction.

Genetics & Inheritance

• OLWS is inherited in an autosomal recessive manner. Homozygous (mutant/mutant) foals are affected and invariably non‑viable. Heterozygous carriers are typically healthy but often display the frame overo coat pattern.

• The frame overo phenotype is incompletely dominant; it may be cryptic when masked by other white-spotting genes or minimal expression—visual phenotype alone is unreliable for carrier identification.

Clinical Presentation & History

• Foals appear normal at birth, but within 12–24 hours, exhibit:

  • Failure to pass meconium

  • Progressive colic signs: abdominal distension, rolling, sweating, tachypnea

  • Rapid deterioration due to intestinal rupture, toxemia, and death or humane euthanasia.

Diagnostic Testing

• Phenotypic suspicion arises from all‑white coat, pink skin, blue eyes, and colic with absent feces—all within hours of birth. However, differential diagnoses include cremellos, sabino-white, and tobiano crosses.

• DNA testing for the EDNRB mutation is definitive for diagnosis—distinguishing homozygous (affected), heterozygous (carrier), and clear animals.

• A necropsy will confirm aganglionosis in the colon and lack of enteric nerve plexus.

Clinical Pathology & Imaging

• No specific biochemical or hematologic signatures.

• Imaging is generally not pursued—obstruction is functional, without a mass—and the course is too rapid for advanced diagnostics in most cases.

NAVLE-Relevant Knowledge Points

• Inheritance patterns: Recognize autosomal recessive lethal trait with heterozygous carriers displaying an incomplete dominant phenotype (frame overo); understand pleiotropy (coat color + enteric neural defect).

• Pathophysiology: Know how neural crest‐derived aganglionosis leads to functional obstruction and colic.

• Clinical signs: Early post‑partum colic, failure to pass meconium in a white, blue‑eyed foal.

• Diagnostic strategy: DNA testing to avoid breeding carriers; importance of genetic-based breeding management.

• Differential diagnosis: Differentiate OLWS from other causes of white coat with blue eyes—e.g., cremello or sabino foals that are viable.

Prognosis & Prevention

• Prognosis is grave—no treatment exists; affected foals die or are euthanized within days.

• Prevention is achievable through genetic testing of breeding stock to avoid carrier × carrier matings.

Further Reading & References

• Merck Veterinary Manual – Ileocolonic aganglionosis (Overo lethal white syndrome)

• Santschi EM, et al. (2001) – “Incidence of the endothelin receptor B mutation…” (Am J Vet Res)

• K. Parry (2005) – “Overo Lethal White Foal Syndrome” (Compendium)

• Keppers & Gonda (2025) – “Lethal white foal syndrome: a review” (Canadian Journal of Animal Science)

• UCDavis Veterinary Genetics Laboratory – Lethal white overo genetic test details

Links:

• Universities Federation of Animal Welfare. Overo Lethal White Foal Syndrome.

• Merck Veterinary Manual. Congenital and Inherited Anomalies of the Small and Large Intestines in Animals.

• Canadian Journal of Animal Science. Lethal White Foal Syndrome.

• UC Davis. Lethal White Overo Syndrome.