Lethal white syndrome

Lethal white syndrome
Other names	overo lethal white syndrome (OLWS), lethal white overo (LWO), overo lethal white foal syndrome (OLWFS)
Healthy horse exhibiting the frame overo pattern.
Symptoms	Nonfunctioning colon, no meconium, colic, fatal within hours to days
Usual onset	Birth
Duration	Hours to days
Causes	Homozygous for "frame" allele on endothelin receptor B (EDNRB); Ile to Lys substitution at codon 118.
Risk factors	If both parents are heterozygotes for frame, there is a 25% probability of an affected LWS foal.
Diagnostic method	Nearly all-white coat at birth, blue eyes, DNA testing, observation for colic, no meconium, pain
Differential diagnosis	Heterozygotes have no known health issues related to the frame allele. Cremello, Dominant white and Sabino-white are normal white or near-white coat colors for healthy horses. Can be distinguished by genetic testing.
Prevention	Avoid breeding heterozygous frame horses to each other
Treatment	None

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; affected foals die within a few days. Because the death is often painful, such foals are often humanely euthanized once identified. The disease is particularly devastating because foals are born seemingly healthy after being carried to full term.^[1]

The disease has a similar cause 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, which 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 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. Also, different genetic mechanisms produce healthy white foals and have no connection to LWS, another reason for genetic testing of potential breeding stock. Some confusion also occurs because the term overo is used to describe a number of other non tobiano spotting patterns besides the frame pattern. Though no treatment or cure for LWS foals is known, a white foal without LWS that appears ill may have a treatable condition.