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Multiple Congenital Malformation in a Holstein Calf
J. Comp. Path. 2003, Vol. 129, 313–315 doi: 10.1016/S0021-9975(03)00044-6, available online at http://www.sciencedirect.com on
SHORT PAPER
Multiple Congenital Malformation in a Holstein Calf D. H. Noh, W. I. Jeong, C. S. Lee, C. Y. Jung, J. Y. Chung, Y. H. Jee*, S. H. Do, M. Y. An, O. D. Kwon, B. H. Williams† and K. S. Jeong College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, *Cheju National University, Cheju City, South Korea and †Armed Forces Institute of Pathology, Washington, DC, USA
Summary A 10-day-old male Holstein dairy calf with orthopaedic abnormalities was unable to stand but was alert with a suckle reflex. At necropsy, the calf showed multiple defects, including partial agenesis of the left rib plate, deformed left scapula, shortened left humerus, agenesis of the left kidney, atresia ani and scoliosis. The cause of these anomalies could not be determined. This report is the first to describe partial agenesis of ribs in a calf. q 2003 Elsevier Ltd. All rights reserved. Keywords: anal atresia; cattle; congenital malformations
A number of different congenital anomalies are known to occur in domestic cattle, and recently several cases of multiple congenital anomalies have been described (Doige et al., 1990; Newman et al., 1999; Lapointe et al., 2000; Agerholm et al., 2001; Duncan et al., 2001). Many of these anomalies have been associated with genetic factors (transgenes, chromosomes), environmental agents (infections, toxins, fertilization techniques, management) or a combination of factors (Jones, 1999; Newman et al., 1999). A 10-day-old male Holstein dairy calf with atresia ani and orthopaedic abnormalities that precluded standing, was submitted to the College of Veterinary Medicine, Kyungpook National University for clinical and pathological evaluation. This calf was the second delivery of the dam and had received surgical treatment for the anal atresia. Clinical examination revealed that the calf was alert with a suckle reflex, but its attempts to stand were unsuccessful. The calf had a slight visible depression of the anterior thorax and had been treated surgically for atresia ani by a field veterinarian. Blood samples were obtained from Correspondence to: K. S. Jeong. 0021–9975/03/$ - see front matter
the calf and dam for serum neutralization tests against Akabane virus (AKV), Aino virus (AIV) and Chuzan virus (CHV). The calf was then humanely killed and subjected to necropsy. This revealed significant anomalies of the left scapula and humerus (Fig. 1). The left scapula blade was transversely narrowed and its overall size (16 £ 8 cm) was smaller than that of the right blade (19 £ 12 cm). The left humerus was 3 cm shorter than the right humerus. Scoliosis was evident in the thoracic spine and agenesis of the first three ribs with exposure of the heart and lungs was present (Fig. 2). Ribs 4 –13 varied in shape and thickness (Fig. 3). The left kidney was not identified and the right kidney was hypertrophic, with a cross-sectional diameter of 11 cm. Samples of brain, heart, kidney, lung and spleen were fixed in 10% buffered neutral formalin, embedded in paraffin wax, sectioned at 4 mm and stained with haematoxylin and eosin. Neutralizing antibodies against AKV, AIV and CHV were not identified in either the calf or the dam. On histopathological examination of the right kidney, glomeruli were seen to be markedly hyperplastic. Several foci of gliosis were seen in q 2003 Elsevier Ltd. All rights reserved.
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D.H. Noh et al.
Fig. 1. Scapula and humerus. Lateral view of the deformed left scapula (arrowhead) and shortened left humerus (arrow). Medial view of the normal right scapula and humerus (R).
the cerebral white matter, but were not considered to be of clinical significance. Lung, heart and spleen were normal. Numerous congenital malformations and deformities of the skeleton (Doige et al., 1990; Agerholm et al., 2001; Duncan et al., 2001) and intestinal tract (Rousseaux, 1994; Lapointe et al., 2000) have been reported in domestic animals. Congenital abnormalities may be multiple (Camon et al., 1990; Newman et al., 1999; Agerholm et al., 2001; Duncan et al., 2001) or may affect single (Doige et al., 1990) parts of organ systems. Multiple congenital anomalies often occur because malformation of one part of the body leads directly to malformation of another (Camon et al., 1990).
Fig. 2. Gross appearance of rib defects with exposure of thoracic viscera (lung—L, heart—H).
Fig. 3. Ribs. Partial agenesis of left rib plate (asterisk). Ribs vary in shape and thickness. The spaces between ribs 4 – 13 also vary.
Moreover, defects may occur in multiple organ systems when a single chromosome carries genetic information important to several metabolic pathways (Rousseaux and Ribble, 1988). Recently, complex vertebral malformation (CVM) in Holstein calves was reported (Agerholm et al., 2001; Duncan et al., 2001). Affected animals had vertebral column anomalies, including hemivertebrae, fused and misshapen vertebrae and ribs, scoliosis, and vertebral synostosis. However, appendicular bone and gastrointestinal and urinary abnormalities were not detected. Genetic, nutritional and environmental factors have been implicated in congenital malformations in calves (Keeler et al., 1981; Doige et al., 1990; Rousseaux, 1994; Jones, 1999; Newman et al., 1999; Lapointe et al., 2000). Morphogenesis and normal cellular differentiation follow a highly synchronized pattern of gene expression and regulation. Recently, ontogenic processes, patterns and their morphological outcomes, such as the formation of embryonic anterior-posterior axis, have been shown to be sequentially directed by the homeobox (segment identity) gene family (Noden, 1991). Deletion or abnormal transcription or translocation of homeotic genes produces a variety of embryonic defects—in Drosophila, generally manifesting as malposition of the body axis or absence of normal posterior structures (Gehring, 1987). The homeobox gene family organized four clusters, Hox 1 through 4 (Goodman and Scambler, 2001), and their sequence has also been found in vertebrates, including the mouse and man (Mahon et al., 1988).
Congenital Malformations in a Holstein Calf
On the farm that provided the specimen described in this report, only one male calf, the dam’s second, had multiple anomalies. Apart from atresia ani, the anomalies occurred in the left thoracic region, representing partial agenesis of the left rib plate, with deformed left scapula, shortened left humerus, agenesis of the left kidney and scoliosis. Therefore, on the basis of phenotypical appearance, the case was considered to be different from CVM. At the time of presentation, all adults and remaining calves on the farm were normal. Moreover, serological evidence of viruses such as AKV, AIV and CHV, which may induce congenital malformations and are reported in South Korea, was not found in either the calf or its dam. Atresia ani has been reported to be due to an autosomal recessive gene or possibly to trauma at pregnancy diagnosis (Rousseaux, 1994; Jones, 1999; Newman et al., 1999). However, no previous cases of atresia ani had been seen on the farm, and no trauma during gestation had been recorded. This report describes a unique syndrome of congenital abnormalities in a calf, affecting the skeletal, gastrointestinal, and urinary systems, and records for the first time unilateral agenesis of a portion of the rib plate.
Acknowledgments This work was supported by the Brain Korea 21 Project in 2003.
References Agerholm, J. S., Bendixen, C., Andersen, O. and Arnbierg, J. (2001). Complex vertebral malformation in Holstein calves. Journal of Veterinary Diagnostic Investigation, 13, 283 –289. Camon, J., Sabate, D., Franch, J., Lopez-Bejar, M. A., Pastor, J., Rutllant, J., Ordeig, J., Degollada, E. and Verdu, J. (1990). Associated multiple congenital malformations in domestic animals. Contribution of four cases. Zentralblatt fu¨r Veterina¨rmedizin, Reihe A, 37, 659 –668.
315
Doige, C. E., Townsend, H. G., Janzen, E. D. and McGowan, M. (1990). Congenital spinal stenosis in beef calves in western Canada. Veterinary Pathology, 27, 16–25. Duncan, R. B. Jr, Carrig, C. B., Agerholm, J. S. and Bendixen, C. (2001). Complex vertebral malformation in a Holstein calf: report of a case in the USA. Journal of Veterinary Diagnostic Investigation, 13, 333–336. Gehring, W. J. (1987). Homeo boxes in the study of development. Science, 236, 1245 –1252. Goodman, F. R. and Scambler, P. J. (2001). Human Hox gene mutations. Clinical Genetics, 59, 1– 15. Jones, C. J. (1999). Perosomus elumbis (vertebral agenesis and arthrogryposis) in a stillborn Holstein calf. Veterinary Pathology, 36, 64 –70. Keeler, R. F., Shupe, J. L., Crowe, M. W., Olson, A. and Balls, L. D. (1981). Nicotiana glauca-induced congenital deformities in calves: clinical and pathologic aspects. American Journal of Veterinary Research, 42, 1231 –1234. Lapointe, J. M., Lachance, S. and Steffen, D. J. (2000). Tibial hemimelia, meningocele, and abdominal hernia in Shorthorn cattle. Veterinary Pathology, 37, 508–511. Mahon, K. A., Westphal, H. and Gruss, P. (1988). Expression of homeobox gene Hox 1.1 during mouse embryogenesis. Development, 104, 187 –195. Newman, S. J., Bailey, T. L., Jones, J. C., DiGrassie, W. A. and Whittier, W. D. (1999). Multiple congenital anomalies in a calf. Journal of Veterinary Diagnostic Investigation, 11, 368 –371. Noden, D. M. (1991). Vertebrate craniofacial development: the relation between ontogenetic process and morphological outcome. Brain, Behavior and Evolution, 38, 190 –225. Rousseaux, C. G. (1994). Congenital defects as a cause of perinatal mortality of beef calves. Veterinary Clinics of North America. Food Animal Practice, 10, 35–51. Rousseaux, C. G. and Ribble, C. S. (1988). Developmental anomalies in farm animals. II. Defining etiology. Canadian Veterinary Journal, 29, 30 –40.
" # Received; January 6th; 2003 Accepted; May 20th; 2003
SHORT PAPER
Multiple Congenital Malformation in a Holstein Calf D. H. Noh, W. I. Jeong, C. S. Lee, C. Y. Jung, J. Y. Chung, Y. H. Jee*, S. H. Do, M. Y. An, O. D. Kwon, B. H. Williams† and K. S. Jeong College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, *Cheju National University, Cheju City, South Korea and †Armed Forces Institute of Pathology, Washington, DC, USA
Summary A 10-day-old male Holstein dairy calf with orthopaedic abnormalities was unable to stand but was alert with a suckle reflex. At necropsy, the calf showed multiple defects, including partial agenesis of the left rib plate, deformed left scapula, shortened left humerus, agenesis of the left kidney, atresia ani and scoliosis. The cause of these anomalies could not be determined. This report is the first to describe partial agenesis of ribs in a calf. q 2003 Elsevier Ltd. All rights reserved. Keywords: anal atresia; cattle; congenital malformations
A number of different congenital anomalies are known to occur in domestic cattle, and recently several cases of multiple congenital anomalies have been described (Doige et al., 1990; Newman et al., 1999; Lapointe et al., 2000; Agerholm et al., 2001; Duncan et al., 2001). Many of these anomalies have been associated with genetic factors (transgenes, chromosomes), environmental agents (infections, toxins, fertilization techniques, management) or a combination of factors (Jones, 1999; Newman et al., 1999). A 10-day-old male Holstein dairy calf with atresia ani and orthopaedic abnormalities that precluded standing, was submitted to the College of Veterinary Medicine, Kyungpook National University for clinical and pathological evaluation. This calf was the second delivery of the dam and had received surgical treatment for the anal atresia. Clinical examination revealed that the calf was alert with a suckle reflex, but its attempts to stand were unsuccessful. The calf had a slight visible depression of the anterior thorax and had been treated surgically for atresia ani by a field veterinarian. Blood samples were obtained from Correspondence to: K. S. Jeong. 0021–9975/03/$ - see front matter
the calf and dam for serum neutralization tests against Akabane virus (AKV), Aino virus (AIV) and Chuzan virus (CHV). The calf was then humanely killed and subjected to necropsy. This revealed significant anomalies of the left scapula and humerus (Fig. 1). The left scapula blade was transversely narrowed and its overall size (16 £ 8 cm) was smaller than that of the right blade (19 £ 12 cm). The left humerus was 3 cm shorter than the right humerus. Scoliosis was evident in the thoracic spine and agenesis of the first three ribs with exposure of the heart and lungs was present (Fig. 2). Ribs 4 –13 varied in shape and thickness (Fig. 3). The left kidney was not identified and the right kidney was hypertrophic, with a cross-sectional diameter of 11 cm. Samples of brain, heart, kidney, lung and spleen were fixed in 10% buffered neutral formalin, embedded in paraffin wax, sectioned at 4 mm and stained with haematoxylin and eosin. Neutralizing antibodies against AKV, AIV and CHV were not identified in either the calf or the dam. On histopathological examination of the right kidney, glomeruli were seen to be markedly hyperplastic. Several foci of gliosis were seen in q 2003 Elsevier Ltd. All rights reserved.
314
D.H. Noh et al.
Fig. 1. Scapula and humerus. Lateral view of the deformed left scapula (arrowhead) and shortened left humerus (arrow). Medial view of the normal right scapula and humerus (R).
the cerebral white matter, but were not considered to be of clinical significance. Lung, heart and spleen were normal. Numerous congenital malformations and deformities of the skeleton (Doige et al., 1990; Agerholm et al., 2001; Duncan et al., 2001) and intestinal tract (Rousseaux, 1994; Lapointe et al., 2000) have been reported in domestic animals. Congenital abnormalities may be multiple (Camon et al., 1990; Newman et al., 1999; Agerholm et al., 2001; Duncan et al., 2001) or may affect single (Doige et al., 1990) parts of organ systems. Multiple congenital anomalies often occur because malformation of one part of the body leads directly to malformation of another (Camon et al., 1990).
Fig. 2. Gross appearance of rib defects with exposure of thoracic viscera (lung—L, heart—H).
Fig. 3. Ribs. Partial agenesis of left rib plate (asterisk). Ribs vary in shape and thickness. The spaces between ribs 4 – 13 also vary.
Moreover, defects may occur in multiple organ systems when a single chromosome carries genetic information important to several metabolic pathways (Rousseaux and Ribble, 1988). Recently, complex vertebral malformation (CVM) in Holstein calves was reported (Agerholm et al., 2001; Duncan et al., 2001). Affected animals had vertebral column anomalies, including hemivertebrae, fused and misshapen vertebrae and ribs, scoliosis, and vertebral synostosis. However, appendicular bone and gastrointestinal and urinary abnormalities were not detected. Genetic, nutritional and environmental factors have been implicated in congenital malformations in calves (Keeler et al., 1981; Doige et al., 1990; Rousseaux, 1994; Jones, 1999; Newman et al., 1999; Lapointe et al., 2000). Morphogenesis and normal cellular differentiation follow a highly synchronized pattern of gene expression and regulation. Recently, ontogenic processes, patterns and their morphological outcomes, such as the formation of embryonic anterior-posterior axis, have been shown to be sequentially directed by the homeobox (segment identity) gene family (Noden, 1991). Deletion or abnormal transcription or translocation of homeotic genes produces a variety of embryonic defects—in Drosophila, generally manifesting as malposition of the body axis or absence of normal posterior structures (Gehring, 1987). The homeobox gene family organized four clusters, Hox 1 through 4 (Goodman and Scambler, 2001), and their sequence has also been found in vertebrates, including the mouse and man (Mahon et al., 1988).
Congenital Malformations in a Holstein Calf
On the farm that provided the specimen described in this report, only one male calf, the dam’s second, had multiple anomalies. Apart from atresia ani, the anomalies occurred in the left thoracic region, representing partial agenesis of the left rib plate, with deformed left scapula, shortened left humerus, agenesis of the left kidney and scoliosis. Therefore, on the basis of phenotypical appearance, the case was considered to be different from CVM. At the time of presentation, all adults and remaining calves on the farm were normal. Moreover, serological evidence of viruses such as AKV, AIV and CHV, which may induce congenital malformations and are reported in South Korea, was not found in either the calf or its dam. Atresia ani has been reported to be due to an autosomal recessive gene or possibly to trauma at pregnancy diagnosis (Rousseaux, 1994; Jones, 1999; Newman et al., 1999). However, no previous cases of atresia ani had been seen on the farm, and no trauma during gestation had been recorded. This report describes a unique syndrome of congenital abnormalities in a calf, affecting the skeletal, gastrointestinal, and urinary systems, and records for the first time unilateral agenesis of a portion of the rib plate.
Acknowledgments This work was supported by the Brain Korea 21 Project in 2003.
References Agerholm, J. S., Bendixen, C., Andersen, O. and Arnbierg, J. (2001). Complex vertebral malformation in Holstein calves. Journal of Veterinary Diagnostic Investigation, 13, 283 –289. Camon, J., Sabate, D., Franch, J., Lopez-Bejar, M. A., Pastor, J., Rutllant, J., Ordeig, J., Degollada, E. and Verdu, J. (1990). Associated multiple congenital malformations in domestic animals. Contribution of four cases. Zentralblatt fu¨r Veterina¨rmedizin, Reihe A, 37, 659 –668.
315
Doige, C. E., Townsend, H. G., Janzen, E. D. and McGowan, M. (1990). Congenital spinal stenosis in beef calves in western Canada. Veterinary Pathology, 27, 16–25. Duncan, R. B. Jr, Carrig, C. B., Agerholm, J. S. and Bendixen, C. (2001). Complex vertebral malformation in a Holstein calf: report of a case in the USA. Journal of Veterinary Diagnostic Investigation, 13, 333–336. Gehring, W. J. (1987). Homeo boxes in the study of development. Science, 236, 1245 –1252. Goodman, F. R. and Scambler, P. J. (2001). Human Hox gene mutations. Clinical Genetics, 59, 1– 15. Jones, C. J. (1999). Perosomus elumbis (vertebral agenesis and arthrogryposis) in a stillborn Holstein calf. Veterinary Pathology, 36, 64 –70. Keeler, R. F., Shupe, J. L., Crowe, M. W., Olson, A. and Balls, L. D. (1981). Nicotiana glauca-induced congenital deformities in calves: clinical and pathologic aspects. American Journal of Veterinary Research, 42, 1231 –1234. Lapointe, J. M., Lachance, S. and Steffen, D. J. (2000). Tibial hemimelia, meningocele, and abdominal hernia in Shorthorn cattle. Veterinary Pathology, 37, 508–511. Mahon, K. A., Westphal, H. and Gruss, P. (1988). Expression of homeobox gene Hox 1.1 during mouse embryogenesis. Development, 104, 187 –195. Newman, S. J., Bailey, T. L., Jones, J. C., DiGrassie, W. A. and Whittier, W. D. (1999). Multiple congenital anomalies in a calf. Journal of Veterinary Diagnostic Investigation, 11, 368 –371. Noden, D. M. (1991). Vertebrate craniofacial development: the relation between ontogenetic process and morphological outcome. Brain, Behavior and Evolution, 38, 190 –225. Rousseaux, C. G. (1994). Congenital defects as a cause of perinatal mortality of beef calves. Veterinary Clinics of North America. Food Animal Practice, 10, 35–51. Rousseaux, C. G. and Ribble, C. S. (1988). Developmental anomalies in farm animals. II. Defining etiology. Canadian Veterinary Journal, 29, 30 –40.
" # Received; January 6th; 2003 Accepted; May 20th; 2003