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Lethal White Syndrome

By: Dr. Mary Rose Paradis

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The lethal white syndrome, intestinal aganglionosis, is an autosomal recessive defect seen in foals from two overo paint parents. The color pattern for overo paints can be confusing, but generally these horses have white coloring under their belly and on the sides of the neck and abdomen. White does not generally cross the back but there are exceptions.

Lethal white foals are characterized by an unpigmented (white) hair coat and light blue eyes (irises), and show intestinal colic in the first few days of life. These foals experience colic because they lack the proper nervous supply (myenteric ganglia) in the terminal portions of the ileum (end of the small intestine), cecum and entire colon (large intestine).
This is due to a defect in the genes that regulate the development of a certain line of embryonic cells that later mature into two types of cells: cells that produce skin pigment (melanocytes) and cells that become the nerves to the end of the small intestine, the cecum and the large intestine. The common genetic link between pigmentation and nerve supply to the intestine explain the lethal white syndrome. Carriers of this gene have also been found in some tobiano and solid colored horses especially if they have overo color patterns in their ancestors.

Affected foals are born with a mostly white coat color, light blue irises and pigmented retinas. Occasionally, small pigmented areas may be present. Foals appear normal at birth, standing and nursing normally. Though some fecal staining may be present at the anus, affected foals do not pass meconium. Colic (abdominal pain) is the primary problem that develops within the first 12 hours of life and becomes progressively worse over the first 24 hours of life. The foal's abdomen is distended with gas because of its inability to pass feces. It is seen with equal frequency in both males and females.

This is a genetic disease. The risk factor for the disease is the breeding of two overo paint horses to each other or the breeding of overo paint to a non-overo that has overo breeding in its pedigree. If two carriers (heterozygotes) for the mutant lethal white gene are bred, there is 25 percent chance of getting a lethal white, 50 percent chance of getting an overo colored offspring and 25 percent chance of having a solid colored off spring.

Diagnosis

The white hair coat and the parentage are fairly strong indicators that you may be dealing with a lethal white foal. Signs of colic in the first day of life accompanied by a distended abdomen also point toward the diagnosis of a lethal white. Small intestinal distention can be seen on radiographs of the abdomen. Other problems that may present with similar colic signs include meconium retention and atresia ani, which is the failure of an anus to form. Your veterinarian will try to eliminate these other causes during the physical examination.

Meconium is the first feces or manure that a foal passes after birth. It is often hard for foals to pass and results in abdominal distention and colic. Meconium impactions can usually be diagnosed and treated with a gentle, soapy water enema. Radiographs of the abdomen may show meconium in the rectum. Intestinal atresia can be diagnosed easily by lifting the foal's tail and looking for an anal opening. It is usually discovered when trying to take the foals temperature. It is unlikely that foals with these other problems would be unpigmented.

Recently genetic testing has been developed to identify the mutation site of the DNA sequence responsible for the lethal white overo foal. The test can be performed on either whole blood or hair samples with roots. Plucked mane and tail hairs are the easiest to obtain. This test can be used to detect carriers, non-carriers and affected animals. Labs currently performing the test include the veterinary schools at University of California, Davis and University of Minnesota.

Treatment

The prognosis is grave; there is no treatment for this genetic disease. Euthanasia is recommended and if not euthanized, they will die naturally within 2 to 3 days. Necropsy (examination after death) of affected foals may show meconium in the colons, gas in the small intestine and contraction of the small colon.

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