Summary
Perosomus elumbis is a rare congenital anomaly of unknown aetiology characterized by the aplasia of the lumbosacral spinal cord and vertebrae, mostly associated with multiple other malformations of the hind limbs and the urogenital and intestinal tracts.
This report describes a stillborn female German Holstein calf showing a complete agenesis of the lumbosacrococcygeal portion of the spinal cord and vertebral column.
In addition, both hind-limbs exhibited arthrogryposis and the musculature was completely replaced by adipose tissue. Furthermore, atresia ani and recti, agenesis of one kidney, one adrenal gland, and a hypoplastic and atretic female genital tract were detected. The aplasia of the lumbosacrococcygeal spinal cord and vertebral column and the other associated malformations in the presented case of perosomus elumbis may be the consequence of a combined developmental disturbance of the caudal neural tube, notochord and paraxial and intermediary mesoderm. However, it remains unclear whether the underlying cause is due to an inherited defect or due to an unknown exogenous factor disturbing embryogenesis in a critical developmental period.
Introduction
Perosomus elumbis is a congenital anomaly characterized by an aplasia of the lumbar and sacral spinal cord and vertebrae. Furthermore, this syndrome is mostly associated with arthrogryposis of the hind limbs due to an ancylosis of the joints and hypoplasia of the musculature (Jones 1999). In addition, other malformations of the urogenital and intestinal tract and the heart are reported (Jones 1999, Castro and others 2003, Gentile and Testoni 2006, Lee and others 2006, Son and others 2008).
Perosomus elumbis occurs most commonly in cattle, but has also been described in sheep, swine and dogs (Son and others 2008, Avedillo and Camon 2007, Cazabon and others 1994, Dennis and others 1975). Bovine perosomus elumbis exhibits the same pattern of malformations as described in human lumbosacral agenesis
(Avedillo and Camon 2007, Lausecker 1952). A rare congenital defect in humans, associated with partial absence of the sacrum, anterior meningocele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad. This malformation is an autosomal dominant trait in man (Lynch and others 2008). The major locus for hereditary sacral agenesis in humans is the homeobox gene HLXB9 (Ross and others 1998). A further reason for an absence of a variable part of the caudal portion of the spine in humans, as it occurs in lumbosacral agenesis or caudal regression syndrome, can be a diabetic status of the mother (Joshi and Yadav 2005).
Concerning bovine perosomus elumbis, Jones (1999) speculated that a possible chromosomal mutation in the homeobox gene family, which has important regulatory roles in anterior-posterior positioning of the neuroectoderm and mesoderm during embryogenesis, could represent the underlying cause (Jones 1999, Holland and Hogan 1988). However, the aetiology of bovine perosomus elumbis remains unresolved so far and warrants further studies. Here we describe a case of bovine perosomus elumbis and discuss possible factors contributing to the pathogenesis.
Materials and Methods
A stillborn black and white German Holstein calf was developed after full term gestation at a slaughterhouse because of dystocia and suspicion of a malformed calf after rectal examination. The dam of the calf gave birth to three healthy calves before and was from a farm with about 60 dairy cows. The farm was free from infectious bovine rhinotracheitis (IBR)-virus and vaccinated against bovine virus diarrhoea (BVD)-virus. There was no case of bluetongue virus infection known in the last years.
The calf was sired by a bull used in artificial insemination.
We performed a complete pathological examination and tissue specimens of various organs were fixed in 10% neutral buffered formalin, processed routinely in paraffin wax, sectioned at 4 µm thickness, and stained with haematoxylin-eosin (HE).
Results
Macroscopic evaluation
The calf was in a mature developmental state, weighing 27.6 kg. The caudal part of the thoracic, and the complete lumbar, sacral and coccygeal vertebral column were missing (Fig. 1). The thoracic vertebral column ended in a compact bony mass formed through a fusion of multiple vertebral bodies, spinous processes and ribs (Fig.
2). A small cavity with a diameter of ~2.5 cm was located within this mass. This cavity was filled with a circumscribed, well-demarcated, bi-nodular mass of nervous tissue, without an obvious connection to the rest of the central nervous system (Fig. 3). The spinal cord displayed an abrupt ending in the cranial part of the third thoracic vertebral body with a dysplastic, conus shaped morphology of its caudal end without a filum terminale (Fig. 3). The abdominal wall caudally of the ribs consisted exclusively of skin, multiple layers of striated musculature and connective tissue elements. The hind limbs were connected to the corpus by soft tissue only.
Arthrogryposis of all hind-limb joints was present due to firm, fibrous joint-capsules and despite inconspicuous articular cartilagineous surfaces. Furthermore, there was bilateral patellar aplasia. Both hind limbs showed total aplasia of the skeletal muscles and replacement by adipose tissue. There was a single, small, blood-filled endothelial cyst within the right artrioventricular valve and agenesia of the abdominal part of the vena cava caudalis. The venous efflux of the caudal body proceeded via a large venous vessel located in the hypodermis of the right thoracic and abdominal wall, interpreted as thoracic vein. The lungs showed total fetal atelectasis. Agenesis of one kidney including ureter and one adrenal gland was found. The remaining kidney displayed a smooth surface, despite the presence of multiple renal papillae on a sectional plane. The urogenital tract consisted of a normal appearing vulva, vagina, urinary bladder and urachus. Furthermore, two caudally fused, blunt-ending cords with a diameter of ~1.5 cm extended from a point near the roof of the vagina ~20.0 cm in a dorsocraniolateral direction (interpreted as remaining Muellerian and Wolffian ducts). Interestingly, the central lumina of these cords exhibited no connection to the urogenital tract. Cranially, one of these cords was connected to the aboral end of the colon, whereas the other opened into the peritoneal cavity. No gonadal anlages were detected macroscopically. We found a blind ending colon with atresia ani and recti.
Histopathology
The macroscopically detected bi-nodular mass within the fused caudal vertebrae displayed a roughly spinal cord-like arrangement of normal appearing neurons, axons, glial and meningeal elements surrounding an ependyma-lined central space.
The skeletal musculature of the hind-limbs was completely replaced by adipose tissue, despite the presence of nerves, vessels and lymph nodes (Fig. 4). The cords extending from the vagina and macroscopically interpreted as Muellerian and Wolffian ducts displayed a central lumen, lined by a non-keratinized, multi-layered squamous epithelium, and surrounded by a thick musculofibrous wall (Fig. 5). Both cords exhibited a symmetric focal expansion of the wall around a nest of tubular and glomerular structures interpreted as mesonephric elements and possibly a regressing Wolffian duct. The normal appearing mucosa of the colon descendens displayed a transition to a non-keratinizing, multi-layered squamous epithelium at the junction of the atretic colon to the small ductular structure interpreted as Muellerian duct (Fig. 6).
The intestinal wall displayed a moderate hyperplasia of the intramural ganglia.
Virology
The examination of multiple organs for BVD-virus and bovine herpes virus-1 employing immunofluorescence microscopy and cell culture technique delivered negative results. Furthermore bluetongue-virus serovar-8-specific RNA-sequences were not detected using RT-PCR.
Discussion
The examined calf exhibited perosomus elumbis with the typical set of malformations including agenesis of the caudal thoracic and lumbosacrococcygeal spinal cord and vertebral column and arthrogryposis of the hind limbs (Castro and others 2003, Jones 1999). The embryonic back consists of the notochord, the neural tube, which is the progenitor of the spinal cord, the paraxial mesoderm, which is the progenitor of the vertebrae and the axial musculature, the intermediary mesoderm, which is the progenitor of the kidneys and the lateral mesoderm (Remagen and others 1970, Stern 1987, Christ 1990, Horster and others 1997, Christ and others 2007). Notably, all structures that develop from the caudal part of the notochord, the neural tube, and the paraxial and intermediary mesoderm are aplastic or malformed in the present
case. The description of a dysplastic caudal end of the spinal cord including agenesis of the filum terminale and a separated nodular neuroglial mass in the present case, further supports the hypothesis of a primary malformation of the neural tube during the tail-bud stage as the cause of perosomus elumbis (Son and others 2008).
Interestingly, the presence of the notochord and neural tube is required for the resegmentation but not the primary formation of the sclerotomes of the paraxial mesoderm (Larsen and others 2006). Ablation studies showed that the removal of both, the notochord and the neural tube, resulted in the formation of a non-segmented, solid vertebral column (Stark 1965), as described for the caudal part of the thoracic vertebrae in the present case. In contrast to the vertebral column, the skeletal muscles of the lateral body wall develop independent of the presence of the neural tube (Hirano and others 1995).
Until present, it remains unclear weather perosomus elumbis has a genetic or an environmental cause. Due to the rarity of this particular defect, epidemiological analyses of possible aetiologic factors have failed so far. Unfortunately, a delayed post-mortem interval prohibited accurate chromosomal analysis in the present case.
Because the homeobox gene family members Hox 2.1 and Hox 3.1 exhibit important regulatory roles in anterior-posterior positioning of the embryonic neuroectoderm and mesoderm, an association of bovine perosomus elumbis and chromosomal mutations in the genes of the homeobox family has been suggested (Jones 1999). In contrast, Dennis (1975) examined 8 cases of ovine perosomus elumbis caused by ingestion of Veratrum californicum. In addition, Padmanabhan (1989) described mice treated with retinoic acid during pregnancy. The newborns showed caudal vertebral defects, imperforate anus, renal malformations, limb malformations, sirenomelia and other defects. Furthermore, a developmental-toxicological study in pregnant rats treated with nitroimidazopyridazine displayed several congenital brain and vertebral column malformations in the neonates caused by defects during neuronal tube formation (Woehrmann and others 2005).
Conclusively, the aetiology of bovine perosomus elumbis remains unresolved so far and warrants further epidemiologic, cytogenetic and molecular studies.
Acknowledgements
The authors are grateful to the staff of the veterinary institute of the regional authorities for consumer protection and food safety of lower Saxony, Hannover, for the virological examinations.
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Kapitel 10
Seltenes Auftreten von Dizephalus, Skoliose und Eisenmenger-Syndrom bei einem männlichen
schwarzbunten Deutschen Holstein Kalb
Bettina Constanze Buck1, Martina Zoeller2, Wolfgang Baumgärtner 2, Ottmar Distl1
1Institut für Tierzucht und Vererbungsforschung, Stiftung Tierärztliche Hochschule Hannover
2Institut für Pathologie, Stiftung Tierärztliche Hochschule Hannover