Congenital Vertebral Malformations
Robert J. MacKay
The vertebral column develops early in gestation via a highly orchestrated series of events comprising, sequentially, notochord formation, neural tube closure, segmentation, and vertebral formation.1,2 Any disruption in this complex sequence by genetic defects, mechanical injury, teratogens, nutrient deficiencies, microbial infections, or maternal illness can lead to abnormalities in the structural anatomy of the spine.
Most congenital vertebral malformations (CVMs) are simple and may go undetected or are discovered incidentally during imaging procedures or at necropsy. In rare cases, a CVM is complex and has serious structural or neurologic implications. CVMs may occur as discrete abnormalities or be part of multiorgan developmental malformations involving neurologic, musculoskeletal, cardiovascular, urinary, or reproductive systems or a combination of these. When symptomatic, CVM is often fatal or life-threatening. Milder presentations predispose affected animals to spinal instability, stenosis, and spinal cord injury.The spine is subdivided into five distinctive series (cervical, thoracic, lumbar, sacral, and caudal).3 Vertebral variants and anomalies are most common around the boundaries between series (i.e., craniocervical, cervicothoracic, thoracolumbar, lumbosacral, and sacrocaudal).3 Patterns of variation reflect the segmental organization of vertebral development under the influence of Hox genes and various growth factors.3
Incidental
Between 13% and 38% of horses have transpositions from C6 to C7 (or occasionally C5) of part of all of one of both ventral processes (also known as ventral laminae of transverse processes).45 Disproportionately high numbers of Thoroughbred and warmblood horses are affected. Although this commonplace homologous variation has been considered incidental, vertebral canal stenosis and cervical pain were found significantly more often in horses with C6 ventral process transposition than in those lacking this anomaly.5 Variations in the dorsal spinous processes of C7 and T1 and malformations of the first rib were also found in only horses with C6 ventral process transpositions.6-8 Of 36 Thoroughbred racehorses, 8 had transitional thoracolumbar (T18-L1) vertebrae and 13 had transitional sacrocaudal vertebrae.9 Numerous other variations in lumbosacral vertebral anatomy were noted, including intertransverse joints and articular process asymmetries.
Transrectal ultrasonography reveals 10% to 20% of horses with ankylosis of L5-L6 or L6-S1 probably have transitional 7vertebrae at those sites.7
Other malformed vertebrae that may be found incidentally can result from failure of sagittal fusion of the vertebral body (i.e., butterfly vertebra10) or dorsal arch (spina bifida occulta). Hemivertebrae (lacking one side of the developing vertebral body) and wedge vertebrae (lacking either ventral or dorsal vertebral component) are more extreme malformations that are rarely asymptomatic.
Symptomatic
The most serious CVMs are disorders of notochord development. These commonly involve multiple different organs, in addition to potentially catastrophic CVMs, including caudal/ sacral agenesis and segmental spinal dysgenesis (aplasia of vertebral bodies).11,12 Perosomus elumbis is a sporadic lethal congenital defect of equids and livestock that includes arthrogryposis and organ malformations in addition to agenesis of vertebrae caudal to the thorax.13-15
CVM syndrome is an inherited condition of Holstein cattle and related breeds caused by a mutation in the gene SLC35A3.16 This mutation manifests as multiple spinal deformities secondary to defective vertebral segmentation along with arthrogryposis, ventricular septal defect, and skull abnormalities. The trait was widely disseminated by the U.S. Holstein sire Carlin-M Ivanhoe Bell and resulted in tens of thousands of abortions and neonatal deaths worldwide before genetic testing was instituted.17 There are numerous reports of congenital syndromes of calves and lambs that phenotypically are similar to CVM. In a few instances, especially when multiple animals were affected, a cause was identified. For example, gene mutations (AGRN gene in Angus cattle and CHRNBl in Danish Red cattle) that cause bovine arthrogryposis multiplex congenita syndromes have been identified.18 Since 2011, fetal infection with Schmallenberg virus has been associated with multiple spinal deformities, arthrogryposis multiplex congenita, and multiorgan malformations in cattle and lambs in Europe.19 Lesions are similar to those described for related bunyaviruses: Akabane virus, Aino virus, and Cache Valley virus.
Other teratogenic viruses of ruminants, including bluetongue, BVD, and border disease, are not known to cause vertebral anomalies. The diagnosis of Schmallenberg viral infection can be supported by specific quantitative PCR, immunohistochemistry and serum neutralization tests on affected neonates. Arachnomelia is another similar autosomal recessive trait with multiorgan involvement and a component of defective segmentation.20 This syndrome is found in Simmentals and Brown Swiss breeds. In addition to scoliosis and kyphosis, affected animals exhibit skull deformities and abnormally thin and elongated “spider” legs. The trait in Simmentals has been localized to a mutation in the MOCSl gene.20Congenital scoliosis, kyphosis, lordosis, kyphoscoliosis, or torticollis are relatively common spinal deformities and, if mild, usually do not cause ataxia.21 These deformities are caused by disorders of alignment or ossification of vertebral precursors (sclerotomes), which lead to asymmetric malformations of the vertebral bodies, articular processes, spinous processes, and ribs. Wedge vertebrae or hemivertebrae cause sharp-angle axial 2223 deviations that predispose to spinal cord compression.22,23 Disordered sagittal fusion of the sclerotome dorsally or ventrally results in defects in the vertebral dorsal arch (spina bifida) or vertebral body (e.g., butterfly vertebrae). Protrusion of the meninges (meningocele), exposure of the spinal cord (myelocele), or both (myelomeningocele) are herniations through the dorsal vertebral defect (spina bifida cystica) and may be apparent as masses on the dorsal midline, either exposed or covered by skin.24-28 Most spina bifida defects are in the lumbosacral spine, although thoracic and cervical examples occur. Spina bifida cystica is associated with neurologic and other abnormalities at and caudal to the lesion, which may be severe. It is hypothesized that chronic CSF leakage into the amnion via the vertebral defect predisposes the affected fetus to hydrocephalus and cerebellar herniations (Arnold-Chiari syndrome) that often accompany spina bifida.29-31 An unusual case in a foal involved herniation of a myelomeningocele ventrally through a defect in the vertebral body.32
Interseries junctions are particularly prone to vertebral variances such as fused or transitional vertebrae (vertebrae with characteristics of adjacent segments).
Many of the changes around cervicothoracic, thoracolumbar, and lumbosacral junctions appear to be asymptomatic, as described in the previous section. In contrast, many CVMs involving the craniocervical junction, including occipitoatlantoaxial malformations,33 cause either stiffness of upper cervical joints (“weathervane posture”) or spinal cord compression and ataxia.Finally, congenitally reduced height of vertebral arches causes vertebral canal stenosis and vulnerability to spinal cord compression.34 Although the vertebral malformations that characterize cervical stenotic myelopathy of horses occur largely after birth, a role for congenital vertebral variations in this condition has not been excluded.
Chapters 51 and 52 contain more information about CVMs.