Lethal white syndrome

Overview

Lethal white syndrome (LWS), also known as overo lethal white syndrome (OLWS), is a fatal genetic condition that affects newborn foals, most commonly in American Paint Horses and related breeds. The syndrome is characterized by an all-white or nearly all-white coat and a non-functioning colon due to intestinal aganglionosis, meaning the absence of nerve cells required for normal gut motility. Foals affected by LWS typically appear healthy at birth but soon develop severe, unrelenting colic and are unable to pass feces. The condition is incurable and invariably leads to death within the first few days of life.

Causes

Lethal white syndrome is caused by a mutation in the EDNRB (endothelin receptor type B) gene. This gene is involved in the development of neural crest cells, which give rise to both pigment cells and enteric neurons in the gut. LWS is inherited in an autosomal recessive pattern, meaning both parents must be carriers of the defective gene to produce an affected foal. When two carriers (typically overo-patterned horses) are bred, there is a 25% chance that the offspring will inherit two copies of the mutated gene and develop LWS.

Symptoms

Foals with Lethal white syndrome typically present the following signs within the first 24 hours after birth:

• Completely or predominantly white coat

• Blue eyes

• Signs of severe colic – including restlessness, pawing, rolling, and excessive sweating

• Failure to pass meconium – the first stool, due to intestinal blockage

• Abdominal distension

• Lack of bowel sounds – indicating intestinal paralysis

Despite appearing normal immediately after birth, these symptoms progress rapidly, often resulting in death within 24–72 hours without intervention.

Diagnosis

Diagnosis of LWS can be made based on clinical signs, physical appearance, and genetic testing. Diagnostic approaches include:

• Physical examination – observing a white coat, colic symptoms, and absence of bowel movements

• Rectal or abdominal radiographs – to confirm intestinal obstruction

• Genetic testing – the definitive diagnosis can be made through DNA testing for the EDNRB mutation, which can also identify carriers

Testing is widely available and recommended for breeding stock to prevent producing affected foals.

Treatment

There is no effective treatment for Lethal white syndrome. Because the condition involves a complete absence of enteric ganglia, the affected foal’s colon cannot function, making surgical correction or medical management impossible. Treatment options are limited to:

• Supportive care – temporarily used in diagnostic stages

• Humane euthanasia – once the diagnosis is confirmed, to prevent suffering from intractable colic

Prognosis

The prognosis for foals with Lethal white syndrome is uniformly poor. All affected foals die or are euthanized within a few days of birth due to the inability of their intestines to function. However, the condition is entirely preventable through responsible breeding practices. Genetic testing of breeding animals, especially those with overo coat patterns, is essential to avoid mating two carriers. By ensuring that at least one parent is not a carrier, breeders can eliminate the risk of producing a foal with LWS.