Equine Familial Isolated Hypoparathyroidism (EFIH)Quick Summary
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Phenotype: Equine familial isolated hypoparathyroidism (EFIH) causes involuntary contraction of muscles and seizures in Thoroughbred foals and is fatal. Clinical signs may also include a stiff gait. Blood work reveals low calcium, typically high phosphorus, and low or inappropriately normal parathyroid hormone (PTH) concentrations, suggesting functional hypoparathyroidism.
Mode of Inheritance: Autosomal recessive
Alleles: N = normal, EFIH = equine familial isolated hypoparathyroidism variant
Breeds appropriate for testing: Thoroughbred
Explanation of results:
- Horses with the N/N genotype do not have the genetic variant causing equine familial isolated hypoparathyroidism and cannot transmit the variant to any of their offspring.
- Horses with the N/EFIH genotype carry one copy of the variant. They appear clinically normal but can transmit the variant to 50% of their offspring, and if mated to another carrier, there is a 25% chance the foal will have this fatal condition.
- Horses with the EFIH/EFIH genotype have two copies of the genetic variant causing equine familial isolated hypoparathyroidism and are likely to suffer from EFIH. This condition is fatal.
Sample Collection
Horse DNA tests are carried out using cells from the roots of a hair sample (roughly 20-30 hairs).
1. Grab about 10 hairs at the base.
2. Wrap the hairs around your finger and give it a quick pull.
3. Check the ends to make sure the pulled hairs have roots.
4. Repeat the process until you have collected about 20-30 hairs with intact roots.
5. You can choose different places on the mane or tail. NOTE: For foals, we recommend pulling all hairs from the tail only.
6. Tape the hairs to the submission form and fold the form along the dotted line to protect the sample. Do not use ziploc bags as they can cause condensation that allows mold to grow on the hair.
7. Place the folded form containing the sample in a paper envelope and mail it to the laboratory.
Equine familial isolated hypoparathyroidism (EFIH), previously termed idiopathic hypocalcemia, causes tetany (involuntary contraction of muscles) and seizures in Thoroughbred foals. Clinical signs may also include a stiff gait and excessive recumbency (laying down). Blood chemistry reveals low calcium, typically high phosphorus, and low or normal parathyroid hormone (PTH) concentrations, indicative of functional hypoparathyroidism. EFIH is invariably fatal: affected foals die or are euthanized due to poor prognosis and/or complications.
The genetic basis for EFIH was discovered in 2019. A nonsense variant in the Rap Guanine Nucleotide Exchange Factor 5 gene (RAPGEF5) replaces a serine in the protein product with a stop codon (c.2624C>A p.Ser875*), leading to a truncated protein with decreased functionality. The direct mechanism by which this loss-of-function mutation leads to hypoparathyroidism has yet to be elucidated, but it is known that RAPGEF5 plays a complex regulatory role in developmental processes and signaling in early embryonic development and is highly expressed in parathyroid tissue.
To date, EFIH has only been identified in the Thoroughbred breed and is inherited as an autosomal recessive trait. This means two copies of the EFIH variant must be present to express this condition. Males and females are equally affected. At the time of publishing, researchers detected the EFIH variant in three out of 82 Thoroughbreds genotyped. The estimated allele frequency in the population is 1.80%.
Genetic testing to screen for horses with the variant can help inform breeding decisions to avoid mating carriers that could produce affected foals and can help confirm clinical diagnosis.