Diprosopus with multiple craniofacial, musculoskeletal, and cardiac defects in a purebred Suffolk lamb

Abstract

A stillborn Suffolk ewe lamb with 2 heads was found to have tarsal arthrogryposis, kypholordosis, craniorachischisis totalis, cheiloschisis, palatoschisis, deviation of the right maxilla, prognathia, patent ductus arteriosus, 3 ventricular septal defects, and 4 great vessels. The lamb was born twin to a normal lamb. No definitive etiology was established.

A stillborn 2-headed lamb was presented for necropsy to the Atlantic Veterinary College. The dam, a 3-year-old, pure- bred Suffolk ewe, delivered a live normal ram lamb unassisted and was noted to be depressed with mild abdominal straining 8 h later. After 1 h of fetal manipulation, a fetus with 2 heads, 1 body with 4 legs, 1 tail, spinal deviation, spinal dysraphism, and bilateral hindlimb arthrogryposis was delivered vaginally by the shepherd (Figure 1). The lamb was then triple bagged and kept frozen until being transported for necropsy. No infectious agents were suspected, as the ewe and normal twin lamb did not display any physical or behavioral abnormalities. The dam had produced a stillborn single ram lamb in the previous lambing season with no obvious abnormalities being noted. The dam was bred to the same purebred service sire in both lambing seasons.

Figure 1.

Stillborn, female, diprosopic, conjoined twin Suffolk lamb. Note the 2 faces, bilateral tarsal arthrogryposis, kypholordosis, and spinal dysraphism.

Necropsy revealed that the diprospic conjoined twin was a female with gross enlargement of the cervix and external genital region. The heads were joined at the occipital region. There were 4 ears, 4 eyes, 2 muzzles, 2 mouths, and 2 mandibles; the 2 medial ears were fused at the base. There were 2 relatively complete cerebrums, which merged caudally to enclose a moderately fused cerebellum. The occipital condyles were abnormally thickened and the foramen magnum was increased in width, allowing the cerebellum to protrude into the cervical spinal canal. The entire spine lacked dorsal processes and appeared wide and flattened dorsoventrally. A wide band of thin fibrous tissue made up the dorsal portion of the vertebral canal. Spinal dysraphism, craniorachischisis totalis, was noted as the skin of the dorsal surface of the spine failed to fuse, leaving the spine and surrounding connective tissue exposed from the caudal cervical area to the lumbar area (Figure 2). Kypholordosis was noted with a ventral deviation of the thoracic spine and a sharp dorsal deviation of the spine at the level of the last rib (Figure 1).

Figure 2.

The entire spine lacked dorsal spinous processes. The skin of the dorsal surface failed to fuse leaving the spine and surrounding connective tissue exposed from the caudal cervical area to the lumbar area. Kypholordosis consisting of ventral deviation of the thoracic spine and a sharp dorsal deviation of the spine at the level of the last rib is present.

The right head had medial deviation of the maxilla, as well as cheiloschisis and palatoschisis, which left a gap in the hard and soft palates, allowing communication between the oral and nasal cavities. The left head also had palatoschisis, as well as prognathia. Each head had a normal tongue and possesed a pharynx, a larynx, and a small epiglottis. The esophagus and trachea were completely separated and merged to form a single and separate esophagus and trachea in the caudal cervical area.

On initial gross inspection, the heart was larger than normal in size. Four great vessels emerged from the heart, which had 2 large ventricles of approximately equal size. The free walls of both ventricles were of similar thickness. The right atrium was moderately distended. Upon opening the heart, each of the 2 vessels that emerged from the right ventricle had separate but closely arranged small narrow openings. These vessels extended in a separate fashion approximately 2.5 cm from the ventricle, then merged to form a single large artery that entered the lung. Two vessels appeared to emerge from the left ventricle. The more medial of the 2 exited the left ventricle from a semi-lunar valve and eventually formed the caudal aorta. The more lateral opened via a small aperture into the right ventricle and continued into the lung. These 2 vessels were connected via a patent ductus arteriosus. A 6-cm long vessel that was approximately 5 mm in diameter, extended from the fused great vessels emerging from the right ventricle to the large aorta. Two small, 2- to 3-mm in diameter, ventricular septal defects were present in the interventricular septa. One was located just below the aortic valve, while the other was present low in the wall, just above the apex. An additional 5-mm septal defect was located within the central septum.

The dam belonged to a semiclosed flock of 20 purebred Suffolk ewes and 1 purebred, registered 2-year-old Suffolk ram. Once daily, the ewes were fed a commercial sheep ration containing 16% crude protein, which consisted of shelled corn, a commercial pelleted concentrate with mineral, oats, and molasses. Second cutting alfalfa/grass hay and mineral salt with selenium were provided ad libitum. Chlortetracycline (Aureomycin; Alpharma, Fort Lee, New Jersey, USA) crumbles were added to the grain portion of the ration during the last 6 wk of gestation at an approximate rate of 40 mg/ewe, for prevention of vibriosis. The ewes had access to 15 acres of winter pasture during the day. The flock was penned overnight in a large group pen and provided with ad libitum hay. The lambing season lasted 7 wk, with all 20 ewes producing lambs. One ewe produced stillborn twins the day before the stillborn 2-headed lamb was born, but no postmortem examination was performed. No other physical abnormalities were observed in the flock.

All lambs had been vaccinated against Clostridium perfringens Types C and D and had received tetanus toxoid at 2 d of age, at the time of docking and castration. Booster vaccinations were administered every 21 to 28 d following the initial vaccination, for a total of 4 vaccinations. Pregnant ewes were not vaccinated and there was no history of infection with Leptospirosis spp. or Campylobacter spp. No outside ewes had been added to the flock in 12 y; all replacement ewes were born and raised on the farm. A new ram lamb was purchased and introduced to the flock every other year. Anthelmintic treatment of all ewes, lambs, and the ram occurred during the 1st week of April, May, June, and August each year: Avermectin (Ivomec; Merial, Duluth, Georgia, USA), 0.2 mg/kg, PO, was administered in April and August, and albendazole (Valbazen; Pfizer, New York, New York, USA), 7.5 mg/kg, PO in May and June. A fenbendazole (Safe-Guard, Intervet, Millsboro, Delaware, USA) anthelmintic and supplement block was utilized in March and October.

The flock had a history of experiencing an unusually high occurrence of inherited anomalies. Twenty-four cases (incidence rate of 21% per 100 gestations) of ringwomb occurred in the flock from 1993 to 1997; the condition was determined to occur where a homozygous recessive fetus was carried by a heterozygous ewe (1). In addition, 1 ewe lamb was born with marked bilateral carpal arthrogryposis in 1999. Doherty et al (2) reported arthrogryposis as an inherited limb deformity in a flock of pedigree Suffolk lambs. Other inherited recessive conditions that had been identified previously on the farm were sexual dimorphism (3), unilateral cryptorchidism (4), and bilateral entropion (4,5). All of the affected lambs in that study were embryo transfer offspring of a single 2-year-old Suffolk ram (2).

Differential etiologies for the congenital anomalies observed in this case consisted of genetic factors, environmental factors, a combination of genetic and environmental factors, and mineral deficiencies. Genetic factors are characterized either by chromosomal abnormalities, which can be diagnosed microscopically, or by mutant genes, which can be identified indirectly by their pattern of transmission. Environmental factors causing congenital defects include viral agents, bacterial agents, irradiation, and drug and plant teratogens. Congenital malformations have been associated with the administration of albendazol from 45 d prior to breeding to 45 d postbreeding at greater than the recommended dosage (6). When the deworming agent parbendazole was administered to sheep at a rate of 60 mg/kg bodyweight on day 24 of gestation, diprosopic and deformed lambs were produced (7). According to the history in this case, albendazol had been administered to the ewe flock 93 d prior to mating. Whole-body doses of gamma radiation administered to ewes between days 22 and 25 of gestation produced deformities of the thoracic limbs in their lambs (8). Exposure of ewes to radiation between days 23 and 27 caused a high occurrence of defective pelvic limbs in their lambs (8). Prognathia and palatoschisis resulted when ewes were irradiated at days 24 and 27 of gestation (8).

The diprosopus abnormality, characterized by the presence of 2 faces with a single head on a single trunk, is one of the rarest craniofacial malformations. A broad spectrum of abnormalities has been described in the literature, with malformations ranging from partial duplication of specific structures, such as the nose, eyes, or mouth, to complete facial duplication. Facial duplication has been associated with other congenital abnormalities, including cleft lip and palate (9), and cardiac defects, particularly ventricular septal defects (10). Embryonic duplications are of importance, because they are usually associated with dystocia and reproductive loss. Although duplications always arouse interest, there is little information available as to their cause.

Every organ passes through a phase in its development, where it displays some variety of labile development. Thus, doubling of a limb, organ, or body system may be induced by exposure to some agent if that agent operates upon that structure at this critical stage in its development.

Diprosopus is believed to be the result of an error related to neurulation of the embryo. The notochord defines the axis of the embryo and induces neurulation. Any disturbances in neurulation can result in failure of neural tube closure (11). The pathogenesis of craniofacial duplication is believed to involve bifurcation or forking of the notochord rostrally, leading to 2, side-by-side oriented, vertebral axes (12) and the formation of 2 neural plates and their neural crest derivatives. The notochordal process elongates and the neural plate broadens and eventually extends cranially as far as the oropharyngeal membrane by about 20 d. The branchial arches develop early in the 4th wk. It is easy to appreciate that these relationships predict the common involvement of the forebrain, mouth, mandible, maxillae, tongue, and thyroid gland.

In conclusion, a definitive diagnosis and etiology is impossible to establish based on only 1 case. However, all abnormal findings in this case, with the exception of diprosopus, consisted of genetic defects previously found to be caused by an autosomal recessive gene (4). In dealing with an individual incident, clinical and postmortem examination of the defective animal is essential to define the abnormality and to ascertain the time of gestation at which normal development ceased. Estimating the time of cessation of normal development may give important clues as to whether the anomaly has a genetic or an environmental basis. In this diprosopic lamb, which presented with multiple craniofacial, musculoskeletal, and cardiac defects, one can estimate that normal development ceased between days 15 and 40 of gestation. The most critical defects likely occurred between days 20 and 30, based on the chronology of normal embryonic development of the lamb and experimental evidence from studies where fetal defects and malformations were induced by drugs and irradiation.