Síndrome del potro lavanda - LFS

Genetic and clinical detail for veterinarians, geneticists and laboratories.

• Gene / locus: MYO5A (myosin VA), ECA1.
• Variant: single-base deletion causing a frameshift and loss of the cargo-binding domain. HGVS (EquCab3.0): NC_009144.3:g.139290592del; XM_023617258.1:c.4249del; XP_023473026.1:p.(Arg1417Alafs*13). The affected protein region is identical in horse, human, mouse and rat.
• Alternative designations: published as c.4459delC (Brooks et al., 2010) and as g.138235715delC on EquCab2.0. c.4459delC and c.4249del are the same deletion numbered against different reference transcripts; quote both when comparing laboratory reports. Laboratory allele symbol: LFS. Disease synonym: Coat Colour Dilution Lethal.
• Variant identifiers: no rs/EVA identifier listed in OMIA; OMIA variant 510.
• Variant classification: not currently evaluated (ISAG/AVCG, per OMIA).
• Inheritance: autosomal recessive (OMIA code R); lethal in homozygotes.
• Penetrance / expressivity: all seven affected foals in the discovery study were homozygous; all eight available parents and 16 of 23 other relatives were heterozygous (Brooks et al., 2010). Heterozygotes are phenotypically normal. The same deletion was found independently in South Africa and confirmed by a different method (Bierman et al., 2010).
• Origin: the affected foals of the discovery study shared a common ancestor six to eight generations back; carriers were later found without that ancestor in their pedigrees, so the founder is probably older. The origin among Egyptian Arabian horses in Egypt was studied by AbouEl Ela et al. (2023).
• Breeds with documented carriers or cases: Arabian (OMIA variant record), concentrated in Egyptian Arabian lines; part-bred Arabians at risk through Arabian ancestry. Not found in 78 Thoroughbreds or 30 Standardbreds (Brooks et al., 2010).
• Allele / carrier frequencies: carrier frequency: 10.3% of Egyptian Arabians (6/58) and 1.8% of non-Egyptian Arabians (1/56), USA; three of these six carriers were breeding stallions (Brooks et al., 2010); 7 of 215 European Arabians (Gabreski et al., 2012); 13.3% of 203 South African purebred Arabians of the 2004/5 foal crop and 11.7% of 197 of the 2009/10 crop, attributed to strong Egyptian Arabian influence (Tarr et al., 2014). Over the same period, SCID carrier prevalence fell significantly after its test became available in 2005, while LFS and cerebellar abiotrophy, tested only from 2009 and 2011, showed no change (Tarr et al., 2014). Carrier surveys have also been published from Poland, Egypt and the wider Middle East and North Africa.
• Clinical / diagnostic notes for veterinarians: affected neonates show seizures, opisthotonus, paddling or stiff limb movements and nystagmus, cannot stand or nurse, and have a dilute coat; pigment is produced but abnormally distributed in the hair shaft. If the coat is overlooked, LFS can be recorded as neonatal maladjustment, sepsis or other neonatal encephalopathy. Gross necropsy is unremarkable, so genotyping of the foal or both parents is the confirmatory test. No immunodeficiency is present, which helps separate LFS from SCID in Arabian foals. Comparative homologues: Griscelli syndrome type 1 (human; hypopigmentation with hypotonia and delayed motor development), dilute lethal mouse, dilute-opisthotonus rat.

Key references:

• Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, Streeter C, Mezey J, Cook D, Antczak DF (2010). Whole-genome SNP association in the horse: identification of a deletion in myosin Va responsible for Lavender Foal Syndrome. PLoS Genet 6(4):e1000909. doi:10.1371/journal.pgen.1000909. PMID 20419149.
• Bierman A, Guthrie AJ, Harper CK (2010). Lavender foal syndrome in Arabian horses is caused by a single-base deletion in the MYO5A gene. Anim Genet 41(Suppl 2):199-201. doi:10.1111/j.1365-2052.2010.02086.x.
• Gabreski NA, Haase B, Armstrong CD, Distl O, Brooks SA (2012). Investigation of allele frequencies for Lavender foal syndrome in the horse. Anim Genet 43:650. doi:10.1111/j.1365-2052.2011.02305.x.
• Tarr CJ, Thompson PN, Guthrie AJ, Harper CK (2014). The carrier prevalence of severe combined immunodeficiency, lavender foal syndrome and cerebellar abiotrophy in Arabian horses in South Africa. Equine Vet J 46:512-514. doi:10.1111/evj.12177.
• AbouEl Ela NH, El Araby IE, Saleh AA, Abd El-Fattah AH, Hagag NM, Brooks SA, Radwan MA, Kalbfleisch T (2023). Evidence for origin of lavender foal syndrome among Egyptian Arabian horses in Egypt. Equine Vet J 55:487-493. doi:10.1111/evj.13604.