Non-KIT white spotting refers to depigmentation patterns in horses caused by mutations in genes other than KIT, most commonly MITF or EDNRB. These mutations affect the development and migration of melanocytes during embryonic development, preventing them from reaching certain areas of the skin and resulting in distinctive white markings. Non-KIT white spotting patterns are often associated with characteristic phenotypes that can vary widely in expression, ranging from minimal white markings to large white areas covering significant portions of the body. Some non-KIT white spotting patterns may also influence eye color. Non-KIT white spotting mutations are typically inherited as autosomal dominant traits, meaning only one copy of the mutation is required for expression. However, expression can vary significantly between individuals, and some mutations may be lethal in the homozygous state.

Frame overo is caused by a mutation in the EDNRB gene. Frame overos have sharply defined, irregular, horizontally oriented white patches. Expression of the frame overo pattern can vary widely. The head is often white or bald-faced, and blue eyes are not uncommon. There are a few frame overo lines in the Thoroughbred breed. Frame overo is autosomal dominant. All adult frame overo horses are heterozygous, carrying only one copy of the gene, and have a 50% chance of passing it down to their offspring. Foals that inherit two copies (homozygous) develop Lethal White Syndrome and die within few days as their intestines don’t develop the nerves needed to move food. Lethal White Syndrome can be completely eliminated by testing all mares and stallions and is 100% preventable through education and responsible breeding. Frame overo gene can be carried without obvious large markings, so carriers cannot always be identified visually. Therefore, genetic testing is essential.