Lavender Foal Syndrome (LFS), or coat colour dilution lethal (CCDL), is a rare and lethal disorder in Arabian horses and crossbreeds. Foals with LFS are born with neurological problems and a lightened coat colour. [1][2][3]

Lavender Foal Syndrome is a genetic condition that is caused by a mutation in the MYO5A gene, which affects nervous system function and skin pigmentation. Foals that inherit two copies of the gene from their parents develop LFS.

There is no cure or treatment available, and the condition is always fatal. Affected foals experience debilitating neurological symptoms, often resulting in euthanasia.

The only way to prevent Lavender Foal Syndrome is with responsible breeding practices and genetic testing in Arabian horse populations. By identifying carriers of the disorder and ensuring they do not mate with each other, the likelihood of producing foals with LFS is reduced.

Lavender Foal Syndrome in Horses

First described in 1996, Lavender Foal Syndrome (LFS) is caused by a fatal genetic mutation that affects the nervous system of Arabian foals.

Foals with LFS exhibit severe neurological signs, including incoordination and seizures. These foals cannot stand to nurse and die shortly after they are born.

Affected foals also display a unique coat colour, often described as a pale or silvery lavender, giving the condition its name.

The genetic mutation responsible for LFS is autosomal recessive, meaning that both parents must be carriers of the defective gene for their offspring to be affected. [3]

Awareness campaigns have been launched in various parts of the world to inform Arabian horse breeders about the importance of genetic testing. By testing potential breeding pairs, the prevalence of LFS can be reduced.

Prevalence

Most foals affected by LFS are Arabian horses from specific bloodlines, notably Egyptian Arabians. This breed sub-group originated in Egypt but is highly sought after in the United States. [1]

Approximately 10.3% of Egyptian Arabian horses and 1.6 – 1.8% of Arabians from other bloodlines are carriers of the gene responsible for Lavender Foal Syndrome.

Arabian Horse Genefits

The Arabian horse is an ancient breed known for its athletic endurance and spirited yet gentle nature. Arabians are distinguished by their dished face, high tail-carriage, arching neck and wide set eyes. [7]

The Arabian breed traces back to several founder horses, notably the “Godolphin Arabian,” the “Darley Arabian,” and the “Byerly Turk.” The extensive use of these founders in breeding led to a high prevalence of certain genetic alleles (mutations) among the Arabian population.

This limited genetic variation was further exacerbated by linebreeding, a selective breeding practice in which related animals are mated to preserve and emphasize desirable traits or phenotypes within a population. [8]

The combination of selective breeding and the Arabian’s limited initial gene pool led to the emergence of several recessive genetic conditions in the breed, including Lavender Foal Syndrome.

However, not all purebred Arabian populations carry the gene mutation responsible for LFS. [9] With genetic testing, responsible breeders can prevent LFS while maintaining the cherished traits of the Arabian breed.

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Clinical Signs

Foals with LFS are easiest to identify by the faded coat colour they display. Affected foals may appear silver, pewter, light chestnut, pale pink or lavender.

The following clinical signs are also reported in foals with LFS: [3][4][5][6]

  • Opisthotonos (backwards arching of the head, neck and spine)
  • Paddling movements with the limbs
  • Recumbency (laying down)
  • General weakness
  • Ataxia (lack of coordination)
  • Difficulty standing and nursing
  • Limb hyperextension
  • Nystagmus (Involuntary eye movements)

Affected foals may have exaggerated spinal reflexes and react strongly to touch. They may suffer from tetanic episodes that mimic seizures, in which the limbs, neck and back extend and contract. These episodes are not considered seizures as the foal’s mental state does not appear to be affected during this time. [6]

Foals with LFS often have difficulty adopting sternal recumbency, a position where the horse lies on its chest and abdomen. Most foals remain in a lateral recumbent position, lying on their side until they eventually pass away. [6]

In cases of Lavender Foal Syndrome, the dam typically has a normal pregnancy, but the delivery can be difficult. Signs of LFS may be mistaken for oxygen deprivation due to difficult birth or a spinal cord injury. [1]

Diagnosis

Diagnosing foals with LFS can be challenging since their initial clinical signs may mimic other neonatal conditions, such as encephalitis (inflammation of the brain). Moreover, LFS-affected foals might have normal clinical parameters, including consistent bloodwork results, further complicating the diagnosis. [1]

Before considering a diagnosis of LFS, your veterinarian will check the foal for signs of trauma, like a head injury, or any skull abnormalities that could be responsible for the neurological symptoms. [3]

The distinct pale coat colour, severe neurological deficits, and non-responsiveness to treatment are key features of LFS that differentiate it from other conditions.

Genetic testing is conducted to confirm a suspected diagnosis of Lavender Foal Syndrome. Your veterinarian will order a DNA test of the affected foal to confirm the presence of the MYO5A gene mutation responsible for LFS.

Differential Diagnosis

Differential diagnosis is the process of distinguishing a particular disease or condition from others that present with similar clinical features. When a foal presents with neurological symptoms, several conditions might be considered, including:

  • Neonatal septicaemia (NS): This life-threatening condition in newborn foals is characterized by a systemic bacterial infection that develops within the first few days of life. Affected foals exhibit a fever, lethargy, fast heart rate, weakness and may be unable to stand or nurse. [13]
  • Neonatal maladjustment syndrome: Also known as dummy foal syndrome this condition occurs when a foal experiences oxygen deprivation or other stressors during birth, resulting in a range of neurological abnormalities. Affected foals are born healthy but develop neurological symptoms shortly after birth, including unresponsiveness, confusion and difficult nursing. [12][14]
  • Occipitoatlantoaxial malformation (OAAM): This developmental defect occurs when the foal’s occipital, atlas and axis vertebrae are malformed or fused in the neck, compressing the spinal cord. This can cause incoordination, abnormal posture, inability to stand or nurse and paralysis of the legs. [12][15]
  • Neonatal Encephalopathy: This is another condition that can cause neurological signs in foals. It might be caused by a variety of factors, including perinatal asphyxia or a lack of oxygen during birth.

Other potential causes of neurological dysfunction in neonatal foals might include metabolic disturbances, toxic exposures, and congenital anomalies. Comprehensive veterinary evaluation and diagnostics are crucial to differentiate these causes.

MYO5A Gene Mutation

Lavender Foal Syndrome is caused by a mutation in the MYO5A gene, which not only affects neurological function but also influences coat colour. The MYO5A gene produces Myosin-Va, a protein essential during embryonic development.

Genes are segments of DNA that provide instructions for the cell to make specific proteins. Genetic mutations arise when alterations in the DNA sequence lead to the production of abnormal or non-functional proteins, potentially affecting the organism’s health and characteristics.

In the case of LFS, affected foals have a single base deletion in exon 30 of the MYO5A gene. This disrupts the synthesis of Myosin-Va, rendering it non-functional.

The MYO5A gene is particularly important during embryonic development, especially in the function of neural crest cells. These unique stem cell later differentiate into melanocytes that determine skin colour and neurons in the brain. [10]

Given the MYO5A gene’s involvement in the development of melanocytes and brain cells, it becomes clearer why foals with LFS exhibit distinct coat colours and suffer from severe neurological issues.

Coat Colour

The pale lavender coat colour seen in foals with LFS results from disrupted melanin transfer to skin cells called keratinocytes.

Myosin proteins are involved in transporting molecules inside cells to ensure they get to the right place. They act like cellular delivery trucks, carrying molecules by “walking” along tracks called actin filaments.

A specific type of myosin, myosin-Va, is predominantly found in skin cells called melanocytes. These cells are responsible for producing melanin, the pigment that colors our skin, hair, and eyes.

Melanin is stored within structures called melanosomes. Myosin-Va is involved in transporting melanosomes to the cell membrane of melanocytes.

Melanosomes are then transferred to keratinocytes, which are skin cells responsible for making keratin, the main structural protein in hair. Keratinocytes and the hair shaft retain melanin, which is what gives hair and skin its colour. [18]

The mutation in the MYO5A gene seen in foals with LFS impairs the transportation of melanosomes within melanocytes. This results in insufficient melanin transfer to keratinocytes, producing the characteristic diluted coat colour of affected foals. [4]

Neurological Function

The MYO5A gene and Myosin-Va protein play a key role in the nervous system. Like its role in skin cells, Myosin-Va is also involved in transporting molecules within neurons.

Neurons communicate by sending signals through chemicals called neurotransmitters. This requires precise and rapid movement of neurotransmitters from the center of the neuron to its outer projections, where these messengers are released to enable neuronal communication.

Myosin-Va is required for proper movement of vesicles that contain neurotransmitters within the neuron. In foals with LFS, the defective Myosin-Va protein can lead to an accumulation of these vesicles. This malfunction disrupts the normal signaling process, causing neurons to release these chemicals at incorrect locations or in wrong amounts. [4]

This significant impairment in neurological function explains the severe mental retardation and movement abnormalities in foals with LFS.

Other Effects

In addition to the unique coat color and neurological dysfunction seen in affected foals, the MYO5A gene mutation associated with LFS has other consequences.

The myosin-Va protein is involved in the function of many other cell types, and not only nerve and melanocyte function. Generally, this protein is responsible for moving vesicles to the edge of cells to allow for the release of their contents.

For example, myosin Va defects can impact insulin secretion by cells of the pancreas. It can also lead to accumulation of waste products within cells, leading to damage and cell death. This has been observed is kidney and liver cells of foals with LFS. [4]

However, given the short lifespan of foals with LFS, the impaired function of other organs may not become apparent.

Genetic Inheritance

LFS is an autosomal recessive condition. This means in order for a foal to be affected, it must receive a copy of the mutated gene from both parents. [3]

Because unaffected horses can still be carriers, the condition is passed on by breeding a mare and stallion that both have a single copy of the mutated MYO5A gene.

Breeding two horses that both carry the MYO5A gene mutation results in:

  • A 25% chance that the foal will have two copies of the mutation and be affected by LFS
  • A 50% chance that the foal will have one copy of the mutation and be a carrier but not affected by LFS
  • A 25% chance that the foal will have two normal copies of the gene and not be a carrier or affected by LFS

Genetic Testing

Genetic testing for Lavender Foal Syndrome should be conducted by Arabian breeders to identify carriers and avoid breeding them together.

The Arabian Horse Health Panel is used to identify carriers of several common diseases in this breed, including LFS, cerebellar abiotrophy (CA), severe combined immunodeficiency (SCID) and occipitoatlantoaxial malformation (OAAM). [17]

The genetic test used to detect the MYO5A mutation was developed in 2009. This test uses polymerase chain reaction (PCR), a laboratory technique that amplifies segments of DNA in order to detect mutations. [1]

Here is a simplified explanation of how PCR testing for LFS works: [11]

Step 1: Sample Collection: A hair sample, often including the follicle (root), is collected from the horse. The follicle contains cells with the horse’s DNA.
 
Step 2: DNA Extraction: The DNA is extracted from the hair follicle cells, separating it from other cellular components.
 
Step 3: DNA Amplification: Using PCR, the specific region of the MYO5A gene associated with LFS is targeted and amplified. This involves the following steps:

  • Denaturation: The double-stranded DNA is heated to separate it into two single strands, revealing the target region.
  • Annealing: Specific primers, or short DNA fragments, (specific to the targeted DNA sequence) bind (or “anneal”) to the single-stranded DNA. These primers act as the ‘start’ and ‘stop’ signals for copying the targeted segment.
  • Extension: The enzyme DNA polymerase synthesizes a new DNA strand, starting from the primers and using the single-stranded DNA as a template.

Annealing and extension are repeated in the PCR process at least 30 times. This creates millions or billions of copies of the section of DNA that contains the MYO5A gene. The final PCR product is used to detect the specific mutation associated with LFS.

Step 4: Detecting the Mutation:

Detecting the MYO5A mutation can be done by sequencing the PCR product to “read” every genetic letter in the DNA sequence and determine whether the single letter deletion that causes LFS is present. [1]

Alternatively, an enzyme, which acts like a specialized pair of scissors, can be used. Researchers will choose an enzyme that cuts at the exact position where the mutation occurs. The enzyme will only be able to do its job if the mutation is present.

After the DNA is treated with the enzyme, the resulting pieces are separated by size. The arrangement or banding pattern of DNA fragments will reveal whether the mutation is present or not. [11]

Interpreting Results

A foal affected by LFS will always have two copies of the MYO5A gene mutation. The foal’s genetic test result will be listed as having an LFS/LFS genotype.

Testing of broodmares and stallions will reveal whether they have the normal MYO5A gene or are carriers of the mutation. These results will be listed as either: [3][12]

  • N/N genotype: A horse with two normal copies of the gene is considered clear or unaffected by LFS. This horse does not carry the mutation responsible for LFS and will not pass it on to its offspring.
  • N/LFS genotype: A carrier horse has one normal copy and one mutated copy of the gene. Carriers do not exhibit symptoms of LFS, but can pass the mutated gene to their offspring. Two carrier individuals should not be bred together, as there is a 25% chance of producing a foal with LFS and a 50% chance of producing a carrier.

Treatment & Prognosis

There is no treatment for Lavender Foal Syndrome, but supportive care may be administered to make affected foals more comfortable. Foals typically die or are euthanized within 72 hours of birth. [1][16]

This severe disorder affects multiple aspects of a foal’s health and development from birth. Despite best efforts at care, many foals with LFS are unable to stand or nurse, which are critical behaviors for their survival in the initial stages of life.

Given the severity of the condition and the suffering it causes, many veterinarians and horse owners opt for humane euthanasia to prevent prolonged distress.

Prevention

Lethal diseases in foals come with significant emotional and economic losses. Egyptian Arabian horses from specific bloodlines are highly sought after, leading to increased inbreeding as breeders try to meet this demand. [1]

The primary measure to prevent the propagation of LFS is through informed breeding practices. Genetic testing, as offered by the Arabian Horse Health Panel, allows breeders to identify carriers of LFS.

By avoiding the mating of two carriers, the risk of producing affected foals is significantly reduced. Additionally, raising awareness and educating breeders about LFS and its implications ensures that informed decisions are made regarding breeding plans.

Summary

  • Lavender foal syndrome (LFS) is a rare and fatal genetic disorder that primarily affects Arabian horses, characterized by neurological symptoms and a light coat colour
  • LFS is inherited in an autosomal recessive manner, meaning both parents must carry the mutated gene for a foal to be affected.
  • Foals with two copies of the mutated gene develop severe neurological symptoms, including ataxia, muscle weakness, difficulty standing and nursing.
  • There is no treatment for LFS, and the condition is fatal with death typically occurring within 72 hours.
  • Responsible breeding practices, including genetic testing of parents, can help eliminate LFS in the Arabian breed.

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References

  1. Brooks S.A. et al., Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome. PLOS Genet. 2010.View Summary
  2. Webb A.A. and Cullen C.L., Coat Color and Coat Color Pattern-Related Neurologic and Neuro-Ophthalmic Diseases. Can. Vet. J. 2010. View Summary
  3. Young A., Lavender Foal Syndrome (LFS). 2020. Accessed Sep. 18, 2023.
  4. Alkalamawy N. et al., Lavender Foal Syndrome in Egyptian Arabian Horses: Molecular and Pathological Studies. SVU-Int. J. Vet. Sci. 2018.
  5. Ela N. et al., Evidence for Origin of Lavender Foal Syndrome among Egyptian Arabian Horses in Egypt. Equine Vet. J. 2022. View Summary
  6. Fanelli H.H., Coat Colour Dilution Lethal (‘Lavender Foal a’): Syndrome Tetany Syndrome of Arabian Foals. Equine Vet. Educ. 2005.
  7. Cosgrove E.J. et al., Genome Diversity and the Origin of the Arabian Horse. Sci. Rep. 2020. View Summary
  8. Ayad A. et al., Investigation of Cerebellar Abiotrophy (CA), Lavender Foal Syndrome (LFS), and Severe Combined Immunodeficiency (SCID) Variants in a Cohort of Three MENA Region Horse Breeds. Genes. 2021. View Summary
  9. Bugno-Poniewierska M. et al., Genetic Screening for Cerebellar Abiotrophy, Severe Combined Immunodeficiency and Lavender Foal Syndrome in Arabian Horses in Poland. Vet. J. Lond. Engl. 1997. 2019. View Summary
  10. Weiner, A.M.J. MicroRNAs and the neural crest: From induction to differentiation. Mech Dev. 2018.
  11. Garibyan L. and Avashia N., Research Techniques Made Simple: Polymerase Chain Reaction (PCR). J. Invest. Dermatol. 2013.
  12. Morales-Briceño A., A Retrospective Study of Mortality Causes in Arabian Horses. Rev. Med. Vet. 2020.
  13. Yan R. and Zhou T., Identification of Key Biomarkers in Neonatal Sepsis by Integrated Bioinformatics Analysis and Clinical Validation. Heliyon. 2022.
  14. Young A., Neonatal Maladjustment Syndrome in Foals. 2021. Accessed Sep. 17, 2023.
  15. Bordbari M.H. et al., Deletion of 2.7Kb near HOXD3 in an Arabian Horse with Occipitoatlantoaxial Malformation. Anim. Genet. 2017. View Summary
  16. Gabreski N.A. et al., Investigation of Allele Frequencies for Lavender Foal Syndrome in the Horse. Anim. Genet. 2012. View Summary
  17. Arabian Health Panel. UC Davis Veterinary Genetics Laboratory. Accessed Aug. 17, 2023.
  18. Benito-Martinez, S. et al. Melanin Transfer and Fate within Keratinocytes in Human Skin Pigmentation. Integr Comp Biol. 2021.