Lethal white syndrome (LWS), also called overo lethal white syndrome (OLWS), lethal white overo (LWO), and overo lethal white foal syndrome (OLWFS), is an autosomal genetic disorder most prevalent in the American Paint Horse. Affected foals are born after the full 11-month gestation and externally appear normal, though they have all-white or nearly all-white coats and blue eyes. However, internally, these foals have a nonfunctioning colon. Within a few hours, signs of colic appear and affected foals die within a few days. Because the death is often painful, such foals often are humanely euthanized once identified. The disease is particularly devastating because foals are born seemingly healthy after being carried to full term.
The disease has a similar etiology to Hirschsprung's disease in humans. A mutation in the middle of the endothelin receptor type B (EDNRB) gene causes lethal white syndrome when homozygous. Carriers, who are heterozygous, that is, have one copy of the mutated allele, but themselves are healthy, can now be reliably identified with a DNA test. Both parents must be carriers of one copy of the LWS allele in order for an affected foal to be born.
Horses that are heterozygous for the gene that causes lethal white syndrome often exhibit a spotted coat color pattern commonly known as "frame" or "frame overo." Coat color alone does not always indicate the presence of LWS or carrier status, however. The frame pattern may be minimally expressed or masked by other spotting patterns. There also are different genetic mechanisms which produce healthy white foals and have no connection to LWS; another reason for genetic testing of potential breeding stock. Though there is no treatment or cure for LWS foals, a white foal without LWS that appears ill may have a treatable condition.
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