Unilateral notomelia in a newborn Holstein calf

Abstract

A 24-hour-old Holstein bull calf with notomelia was donated to the Atlantic Veterinary College. The extra limb was on the right side of the caudal neck adjacent to the withers. The limb was surgically removed under general anesthesia. The calf was adopted and discharged with no complications.

A 24-hour-old Holstein bull calf was referred to the AtlanticVeterinary College (AVC) for evaluation of a supernumerary limb. The calf was born on a small-scale dairy farm with no prior history of polymelic calves. The calving was recorded as normal. The calf was born with a small fully formed forelimb on the right side of the caudal cervical region adjacent to the withers (Figure 1). All other parameters were within normal limits at birth. The calf suckled and drank colostrum normally. Due to the decreased economic value of the animal and the rare congenital defect, the calf was donated to the AVC for assessment.

Figure 1.

Newborn Holstein bull calf with supernumerary limb (notomelia) attached to the caudal cervical region.

Case description

Upon presentation to the AVC, the calf was quiet, alert, and responsive. Pulse, temperature, and respiratory rates (60 beats/min; 38.6°C; 20 breaths/min) were all within normal limits. No abnormalities were noted on pulmonary and cardiac auscultation. Capillary refill time was normal (< 2 s). Fecal staining was evident on the perianal region indicating the calf had defecated. The umbilicus appeared healthy and was regressing normally. A 50% chlorhexidine solution was applied to the umbilicus. The calf had a weak suckle reflex and was treated according to standard protocol. Selenium and vitamin E supplementation was administered (Selon-E, 3 mg/mL; Vétoquinol, Lavaltrie, Quebec), 1 mL, IM.

Clinical examination revealed that the supernumerary limb was to the right of midline at the level of the withers with no boney attachment. The limb was approximately half the length of the thoracic limbs and appeared fully developed with only 1 claw. There was limited motion in the joints with no detectable motor control or sensation in the limb.

Three days after presentation the calf was taken to surgery to remove the extra limb. The calf was placed in sternal recumbency under general anesthesia and the limb was removed by routine surgical methods. The tissues isolated and incised were the skin, subcutaneous tissue, a thin fibrous band, and vessels connecting the limb to the body. Recovery from anesthesia was uneventful. Postoperative pain medication was administered (Anafen, 100 mg/mL; Merial, Baie d’Urfé, Quebec), 2.2 mg/kg body weight, IM.

A single lateral radiographic view of the limb was obtained after the limb was removed from the body (Figure 2). Radiographically, the humerus was fused with the radius and ulna, which were also fused. A distinct humeral head was visualized. Open growth plates were noted in both the proximal humerus and the distal radius. A well-formed olecranon process was seen but it lacked a normal physeal line. The carpal bones consisted of a single large well-mineralized oval-shaped bone. A single metacarpal bone and solitary first, second, and third phalanges were present. A gross pathological examination was carried out on the removed limb. The soft tissue component of the limb consisted primarily of adipose tissue with a minute amount of striated muscle and no well-defined, identifiable muscles.

Figure 2.

Single lateral radiograph of the supernumerary limb removed from the caudal cervical region of the newborn Holstein bull calf.

Discussion

The incidence of congenital malformations in common domestic livestock is estimated to range from 2% to 3.5% of all births. The frequency of these abnormalities varies with species, breed, geographical location, and other environmental factors (1). In cattle, the most common congenital malformations are associated with the musculoskeletal system and constitute 24% of malformations (2).

Polymelia is a rare congenital malformation that is defined as the formation or presence of a supernumerary limb. It can be characterized based on where the limb is attached: notomelia has an attachment to the region of the embryological notochord, which contributes to the development of the axial skeleton and becomes the nucleus pulposus of the intervertebral disc (3), cephalomelia has attachment to the head, thoracomelia has an attachment to the thorax, and dygomelia has an attachment to a limb attached to the pelvis (4). In this case, the supernumerary limb was attached at the level of the withers classifying it as notomelia. Polymelia has been reported in various mammals, birds, and amphibians (5–11).

Polymelia is often associated with other musculoskeletal defects such as polydactyly, syndactyly, presence of additional bones that are often underdeveloped, and absence of bones (7,10,12,13). In this report, the supernumerary limb was smaller than the normal limbs with a fused humerus, radius, and ulna, 1 carpal bone, metacarpal bone, and only 1 set of phalanges. The scapula and scapulohumeral joint and cubital (elbow) joint were absent. The carpal joints were abnormal due to the presence of a sole carpal bone. One claw was present with limited movement in the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints.

A limb is the product of an outgrowth or bulge of the lateral body wall known as the limb bud, which initially consists of mesenchymal cells derived from the local somatic lateral plate mesoderm, and is covered by ectoderm. At the tip of the limb bud the ectoderm is thickened and is known as the apical ectodermal ridge (AER). The outgrowth of the limb depends on the interaction between the AER and the underlying mesoderm, as well as on a series of signaling pathways and molecules, such as fibroblast growth factor-8 (Fgf-8), T-box transcription factor-4 (Tbx-4), Tbx-5, and Fgf-10, that play essential roles (3,14). In early stages of development, the underlying mesenchymal cells originate solely from the somatic lateral plate mesoderm that eventually gives rise to the bones, connective tissue, and blood vessels of the limb. In a second phase of development, mesenchymal cells from the differentiating somites (myotomes) migrate into the limb bud and give rise to skeletal/striated muscles. The nerve cells in the limb are the result of cell migration from the neural crest that develops into Schwann cells of the nerves and melanocytes (3,14). Alterations in any of the aforementioned events and structures can result in abnormalities.

Radiographic examination revealed the supernumerary limb in this case had abnormal bone formation with fused bones, lack of growth plates in normal areas, lack of carpal bones, and only 1 digit. Talamillo et al (14) reported that the size and pattern of the limb are influenced by the number of progenitor cells that initiate the limb bud, the rate of the cell proliferation, and the amount of cell death. If these are not regulated with the help of growth proteins and signaling pathways, the resultant limb will have alteration from the normal pattern of the autopodium and the number of digits for that animal (14). The finding that nervous tissue was absent, muscle tissue was minimal, and most of the tissue was adipose tissue suggests that there were also deficits in or lack of migration of cells from the neural crest as well as migration of the mesenchymal cells from the myotomes.

Congenital defects manifest when there is a disruption in the normal events at one or more stages of embryo and fetal development (2,11). The specific etiology of polymelia is not known. It is speculated that the occurrence is multifactorial. Genetic, environmental, or a combination of both factors is believed to result in the development of a supernumerary limb. Genetic defects such as mutant genes (i.e., abnormal expression of genes) or chromosomal abnormalities (i.e., fragility) are suggested in the literature (13,15–18). Due to the lack of genetic evaluations on reported bovine cases of polymelia, there is no specific evidence to support these theories. Environmental factors such as toxins, infectious agents, and chemicals have been reported in the development of congenital musculoskeletal defects (19,20). There is, however, no consistency among cases reported. Interestingly, there is a suggested gender-linked component in bovine polymelia. Several studies have reported this to most commonly occur in females (2,10). The calf in this case study, however, was a male suggesting the lack of a gender-linked component with this condition.

A major concern with production of purebred livestock is the potential for inbreeding and genetic defects. Focus is particularly on the over-use of popular sires with desirable traits in the dairy industry through the common practice of artificial insemination. Many breeding programs can investigate inbreeding by measuring the inbreeding coefficient of an individual animal (21). Breeding records obtained in this case indicated that inbreeding was not a factor. There were no common ancestors in 4 generations of this animal; thus, the inbreeding coefficient is extremely low for this calf. One study on amphibians suggested that reduction in genetic diversity from inbreeding is not a causal mechanism of malformed individuals in that particular species (22).

Teratogens have been implicated in the occurrence of congenital defects. Typically the fetus is most susceptible to a teratogen in the first trimester of pregnancy. Exposure to specific plants, drugs, and infectious agents has been reported to result in various musculoskeletal abnormalities. Plants, such as locoweeds (Astragalus spp.), poison hemlock (Conium spp.), and lupines (Lupinis spp.) are known to cause congenital musculoskeletal defects in livestock (23–25). None of the aforementioned plants, however, have been linked directly to polymelia. Medications have been suspected in the development of polymelia; however, thalidomide in humans is the sole drug known to cause polymelia and other abnormalities (26). Various infectious agents, such as pestivirus, arbovirus, and orbiviruses, are causative agents in musculoskeletal abnormalities in several livestock species (27). However, no specific infectious pathogen has been isolated in causes of polymelia in livestock. Teratogens, even though not identified, are highly suspected in polymelia cases. This may be the result of the sporadic occurrence of this condition and further investigations will be needed to determine etiologies.

Polymelia carries a good prognosis as the defects are localized to the musculoskeletal system. Other organ systems are rarely affected unless the animal is determined to be the result of twinning in which case internal organs can be affected as well (2). Animals can survive with the supernumerary limb as long as it does not impede locomotion. Conversely, the extra limb can be surgically removed with minimal complications (5,13,28).