Published August, 2011

A new foal's arrival is an exciting time. After 11 months of gestation and caring for the mare and watching her belly expand, delivering a healthy foal is one of the best experiences for a horse owner. Sometimes, however, foals are born with flexural limb deformities (FLD). Many of these foals present with severe FLD called contracted foal syndrome (CFS), which in its worst form involves all four limbs, the neck (torticollis), skull (wry nose), and spine (scoliosis). One third of these foals will be euthanized. However, other less severely affected foals with only one or two affected limbs involved might recover with surgery, splinting, and therapy.

The availability of the horse genome sequence and the subsequent development of genomic tools have facilitated a study of FLD/CFS led by Teri Lear, PhD, associate professor in the genetics/genomics group at the University of Kentucky (UK) Gluck Equine Research Center. Collaborators on the study include Ernie Bailey, PhD, professor in the genetics/genomics group at the Gluck Center; Uneeda Bryant, DVM, assistant professor in pathology at UK's Veterinary Diagnostic Laboratory (UKVDL); Craig Carter, DVM, PhD, Dipl. ACVPM, director of the UKVDL; Steve Reed, DVM, Dipl. ACT, Rood & Riddle Equine Hospital; and Luigi Auletta, a visiting veterinarian from Italy working at Rood & Riddle.

"We have collected DNA samples from affected foals for a pilot study," Lear said. "All of the foals had all four limbs affected and most had scoliosis, wry nose, and torticollis. Our preliminary results highlighted three regions on three different chromosomes indicating the condition is complex and may involve multiple genes. Genomic testing is expensive, and we still need to test many more horses to hone in on the candidate genes that might cause FLD/CFS."

This condition has been reported primarily in Thoroughbreds but also occurs in Standardbreds, American Saddlebreds, Quarter Horses, and other breeds. Males appear to be more commonly affected, and multiple affected limbs occur more often than a single affected limb. To make matters worse, foals with FLD/CFS can be a serious risk to mares during birth. Up to 16% of dystocia (difficult birth) cases might be due to FLD/CFS affected foals. This might require the mare to undergo a Caesarian, or C-section, increasing her risk of death.

The cause of FLD/CFS in horses is unknown. Muscle, tendon, and ligament tissues appear normal when examined microscopically by pathologists. Theories as to the cause include uterine insufficiency, exposure to toxins during embryonic development, dietary issues, and viral infections of the mare during pregnancy. However, recent family studies suggest the condition could be inherited. Some mares have produced up to four affected foals even when each foal is sired by a different stallion and the mare has been housed on different farms. This rules out a management component to the disorder. Individual cases suggest the condition might be inherited in a dominant fashion, but might not always develop depending on other genetic factors. This could explain why some foals have the milder form of CFS than do others.

The skeletal anatomy of a horse's leg is comparable to the anatomy of the human hand and foot. A horse essentially walks on the equivalent of a human finger or toe. The horse's cannon bone, or metacarpal, is similar to a bone in the palm of your hand. The human phalanges, or finger bones, are comparable to the bones that comprise a horse's hoof and pastern. If a child is born with tightly clenched fists and club feet, he or she might have one of several muscle contracture syndromes known collectively as distal arthrogryposis (DA). The child might also have other congenital abnormalities such as spinal curvature (scoliosis), facial muscle contractures, and a small mouth. Most children are of normal intelligence but others have developmental retardation.

Mutations in one or more genes that control skeletal muscle contraction cause DA in humans. These gene mutations produce abnormal muscle protein that disrupts normal muscle function during fetal development, resulting in limb contractures. The skeletal muscles contract, but are unable relax as normal muscles do. Most of the mutations are inherited, but their mode of inheritance can vary. Marked variation in clinical signs within and between families might occur. Mutations also can arise spontaneously as new or "de novo" mutations. Some children with DA respond to surgery and physical therapy, while others do not.

The varying levels of severity and clinical signs displayed by a horse with CFS are similar to those seen in human DA. Some affected foals undergo treatment and have complete remission. About a third of these foals go on to have performance careers, but another third die or are euthanized prior to one month of age. FLD/CFS continue to be the most common congenital abnormality diagnosed at UK's Veterinary Diagnostic Laboratory.

Our future success will depend on support from the horse industry in providing research samples and funds to carry out a larger study. All information is kept confidential including horses' and farms' identities. We expect, one day, to develop a diagnostic test that will help farm managers avoid matings that might produce affected foals and to determine which foals will respond to treatment. The participation of breeding farms, veterinarians, and horse owners is imperative if the causes of FLD/CFS are to be understood.

CONTACT: Teri L Lear, PhD, 859/257-4757, ext. 81108, equigene@uky.edu, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington.

Teri Lear, PhD, associate professor in the genetics/genomics group at the Gluck Equine Research Center, provided this information.