Lethal white foal syndrome: a review

A congenital abnormality most commonly associated with frame overo American Paint horses is termed overo lethal white foal syndrome, lethal white foal syndrome (LWFS), or lethal white overo syndrome, where foals homozygous for a missense Ile118Lys mutation in endothelin-B receptor gene are born completely white with an abnormal intestinal tract. Parents with frame overo phenotype are at higher risk of producing overo lethal white foals; however, some breeds not known for spotted pattern phenotypes have also produced LWFS foals. The neural crest cells of affected foals do not differentiate into melanocytes and enteric neuronal ganglions leading to the phenotypic presentation. As the disease progresses, a lack of neuronal innervation at the intestinal obstruction leads to intestinal rupture, toxicity, and death. No cure for this disease is known. The disease can be prevented through genetic testing of parents whether from overo lineage or not. Other examples of disease models similar to LWFS include Hirschsprung disease and Waardenburg Shah Syndrome in human medicine and piebald lethal in mice and lethal spotting in rats.