Thoracic Vertebral Malformations Research Articles

Prevalence and classification of congenital thoracic vertebral body abnormalities in neurologically normal brachycephalic 'screw-tail' dog breeds in referral practice in Australia.

To evaluate the prevalence, type, site and breed predisposition of thoracic congenital vertebral malformations (CVM) in neurologically normal brachycephalic 'screw-tail' dog breeds. Retrospective case series. Neurologically normal French Bulldogs (n = 63), British Bulldogs (n = 42), Boston Terriers (n = 4) and Pugs (n = 86) presenting for brachycephalic obstructive airway syndrome treatment. Either a plain computer tomography scan of the thorax or lateral and dorso-ventral digital radiographs of the thoracic vertebral column of each dog were assessed for any vertebral malformations and classed according to the Modified McMaster vertebral abnormality classification scheme proposed by Guiterrez et al. RESULTS: The prevalence of dogs with one or more abnormal vertebrae was 96.82% in French Bulldogs, 90.47% in British Bulldogs, and 76.74% in Pugs. Pugs had significantly lower instances of CVMs than French Bulldogs. The four Boston Terriers all had vertebral malformations, but the results were not considered to be statistically significant due to their small sample size. In French Bulldogs and British Bulldogs, ventral hypoplasia (Type 3) occurred at greater rates than all other types, followed by ventral and median hypoplasia (Types 7) and symmetrical hypoplasia (Type 8). In Pugs, symmetrical hypoplasia (Type 8) was the most common and then ventral hypoplasia (Type 3). The most affected vertebrae were T6-T9 in Pugs and T5-T10 in French Bulldogs and British Bulldogs. The majority of neurologically normal brachycephalic 'screw-tail' dogs assessed in this paper possessed one or more congenital thoracic vertebral malformations. Dogs with vertebral malformations were found to be more likely to have more than one affected vertebra. Sex had no effect on the prevalence of CVM. A substantial number of neurologically normal brachycephalic 'screw-tail' dogs suffer from congenital vertebral malformations. Thus, the need for selective breeding programmes to eliminate this hereditary condition is crucial.

Perioperative epidural catheter analgesia as a component of a multimodal analgesic approach in a dog with thoracic hemivertebrae and kyphosis undergoing thoracic vertebral stabilisation

AbstractA 4‐year‐old, male, neutered French bulldog weighing 13.5 kg presented with urinary and faecal incontinence, progressive, non‐painful paraparesis and pelvic limb proprioceptive ataxia. Magnetic resonance imaging revealed a T12 constrictive myelopathy in association with multiple thoracic vertebral malformations, and mildly impinging thoracic intervertebral disc protrusions. Additionally, there was a sacral axial defect and degenerative lumbosacral stenosis. Surgical treatment comprised bilateral dorsal vertebral stabilisation of T9–T13. This case report summarises the peri‐anaesthetic management, which included an ‘in‐plane’ ultrasound‐guided placement of an epidural catheter at the level of L3–L4 and advancement cranially to T12 as a component of a multimodal analgesic regimen. Following the cessation of postoperative epidural bupivacaine administration, the patient remained comfortable without requiring rescue analgesia, and was discharged within 24 hours of surgery. At the latest recheck 5 months after surgery, the dog's neurological status remained static. This technique and application remain unexplored in existing veterinary literature.

Transthoracic Vertebral Distraction and Stabilization in 10 Dogs with Congenital Thoracic Vertebral Malformations.

The aim of this study was to describe the surgical technique and outcomes of dogs with congenital thoracic vertebral body malformations (CTVBM) treated with unilateral vertebral distraction and stabilization with monocortical screws and polymethylmethacrylate (PMMA). Medical records of 10 client-owned dogs with CTVBM were retrospectively searched for signalment, history, neurological examination, neurological grade based on the modified Frankel scale (MFS), diagnostic method, CTVBM location, Cobb's angle, and vertebral canal angle (VCA), surgical procedure, complications and long-term follow-up. One dog suffered cardiac arrest 24 hours post-surgery and died. Median follow-up in nine dogs was 26.5 months (12-50 months). Cobb's angle improved from 33-83 to 10-46 degrees and the VCA ratio from 97-138 to 122-164 degrees. The MFS improved from 3 (n = 3)-4 (n = 7) to 4 (n = 2)-6 (n = 7). Seven dogs recovered full function. Nine dogs improved after surgery compared with preoperative status, recovering ambulation when lost or achieving normal neurological examination in seven cases. No complications were reported during the follow-up period (12-50 months). Unilateral transthoracic vertebral distraction and stabilization with monocortical screws and PMMA for treatment of compressive myelopathy due to CTVBM achieved long-term neurological improvement in 9 of 10 dogs.

Prevalence of congenital scoliosis in infants based on chest–abdomen X-ray films detected in the emergency department

To investigate the prevalence of congenital scoliosis (CS) in infants based on chest-abdomen radiographs. A retrospective review was conducted on infants in the emergency department (ED) of a tertiary children's hospital between February 2008 and September 2019. Patients who had undergone chest-abdomen X-rays were included. All films from the enrolled patients were screened for CS. Their demographic characteristics, type, and location of the vertebral and rib anomalies, and concomitant defects of other systems were analyzed. In total, 50,426 infants were enrolled; 89 (1.8‰) were diagnosed with CS, including 56 males and 33 females. There was no gender difference in CS prevalence. The visiting age of the CS patients (70 ± 98days) was significantly younger than that of the non-CS group (P < 0.05), with CS patients mainly visiting for digestive (53.9%) and respiratory symptoms (41.6%). Sixty-eight (76.4%) CS patients had main thoracic (T6-T11) vertebral malformations. Rib anomalies were documented in 27 (30.3%) patients, of which 14 had complex rib anomalies. Forty (44.9%) patients had concomitant defects of other organs, of which eight patients had two systemic abnormalities mixed. The most common extraspinal defects were imperforate anus (21, 23.6%) and congenital cardiac defects (17, 19.1%). The prevalence of CS in infants based on chest-abdomen X-rays in the ED was 1.8‰. Both the vertebral and rib anomalies mainly affected the main thoracic region. The spine deformities in infants with concomitant defects of other organs could be identified earlier because of early-onset symptoms, which also bring out a selection bias in our analysis.

Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10−37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.

Outcomes of nonsurgical treatment for congenital thoracic vertebral body malformations in dogs: 13 cases (2009-2016).

OBJECTIVE To characterize outcomes following nonsurgical treatment of congenital thoracic vertebral body malformations causing neurologic deficits in dogs. DESIGN Retrospective case series. ANIMALS 13 client-owned dogs treated nonsurgically for congenital thoracic vertebral body malformations at 3 veterinary referral hospitals from June 2009 through May 2016. PROCEDURES Data were extracted from the medical records regarding dog signalment, duration and type of clinical signs before referral, general physical and neurologic examination findings, radiographic and MRI findings, and treatments provided after diagnosis. Follow-up data were obtained from records of recheck examinations and via a standardized owner questionnaire. RESULTS All included dogs were screw-tail brachycephalic breeds with a median age of 6 months. All dogs had ambulatory paraparesis and ataxia, and in 1 dog, signs of spinal hyperesthesia could be elicited. Nonsurgical treatments consisted of restricted exercise without (n = 5) or with (3) physiotherapy, physiotherapy without restricted exercise (3), and no exercise modification (2). Seven dogs received additional nonsurgical treatment consisting of prednisolone (n = 5) or gabapentin (2). Four dogs were eventually euthanized because of progressive neurologic deterioration, 2 underwent surgery for the same reason, and the remaining 7 dogs survived for ≥ 170 days after diagnosis, despite progressive neurologic deterioration. CONCLUSIONS AND CLINICAL RELEVANCE Nonsurgical treatment of congenital thoracic vertebral body malformations was associated with an unfavorable outcome in this group of dogs. Despite this treatment, all dogs had progression of clinical signs.

Presence of thoracic and lumbar vertebral malformations in pugs with and without chronic neurological deficits

Congenital vertebral malformations (CVMs) are common in brachycephalic dogs such as the pug, and are often considered incidental findings. However, specific CVMs have been suggested to be associated with neurological deficits in pugs. The objective of this study was to investigate the clinical importance of CVMs in the pug by comparing computed tomography studies of the thoracolumbar spine from pugs without neurological deficits with those from pugs with a confirmed T3-L3 spinal cord lesion and neurological deficits consistent with a chronic T3-L3 myelopathy.A total of 57 pugs were recruited into the study from Sweden (n=33), United Kingdom (n=21) and Norway (n=3); 30 with neurological deficits and 27 without. Focal T3-L3 pathology was confirmed in all pugs with neurological deficits by magnetic resonance imaging (n=29) and/or pathology (n=15). Computed tomography studies of the thoracolumbar spine from pugs with and without neurological deficits were compared to investigate possible associations between presentation of neurological deficits consistent with chronic T3-L3 pathology and signalment variables, presence of CVMs and type of CVMs. Congenital vertebral malformations were as common in pugs with, as in pugs without, neurological deficits. Regardless of neurological status, the majority of pugs (96%) presented with one or more CVM. An association between presence, or type of CVM in the T1-L3 vertebral column, and neurological deficits consistent with T3-L3 pathology could not be confirmed.

Radiographic assessment of the congenital thoracic vertebral malformations in French bulldogs

Radiographic assessment of the congenital thoracic vertebral malformations in French bulldogs

Evaluation of the influence of kyphosis and scoliosis on intervertebral disc extrusion in French bulldogs

BackgroundAlthough thoracic vertebral malformations with kyphosis and scoliosis are often considered incidental findings on diagnostic imaging studies of screw-tailed brachycephalic breeds, they have been suggested to interfere with spinal biomechanics and intervertebral disc degeneration. It is however unknown if an abnormal spinal curvature also predisposes dogs to develop clinically relevant intervertebral disc herniations. The aim of this study was to evaluate if the occurrence of thoracic vertebral malformations, kyphosis or scoliosis would be associated with a higher prevalence of cervical or thoracolumbar intervertebral disc extrusion in French bulldogs.ResultsFrench bulldogs that underwent computed tomography for reasons unrelated to spinal disease (n = 101), and French bulldogs with thoracolumbar (n = 47) or cervical intervertebral disc extrusion (n = 30) that underwent magnetic resonance imaging were included. There was a significant association between the presence of kyphosis and the occurrence of intervertebral disc extrusion, particularly in the thoracolumbar region. Dogs with kyphosis were at nearly a two times increased odds of being affected by intervertebral disc extrusion than those without kyphosis [(OR = 1.98 (95% CI: 1.04–3.78)]. There was also an association between the presence of scoliosis and the anatomical distribution of intervertebral disc extrusions, with dogs with scoliosis more likely to have more caudal lumbar intervertebral disc extrusions. Presence of scoliosis was not associated with an increased odds of being affected by intervertebral disc extrusion.ConclusionsAlthough thoracic vertebral malformations with kyphosis only rarely cause spinal cord dysfunction in itself, French bulldogs with kyphosis appear to be at higher risk to develop thoracolumbar intervertebral disc extrusion.

Prevalence of thoracic vertebral malformations in French bulldogs, Pugs and English bulldogs with and without associated neurological deficits

Congenital vertebral malformations are common incidental findings in small breed dogs. This retrospective observational study evaluated the type and prevalence of thoracic vertebral malformations in 171 neurologically normal and 10 neurologically abnormal screw-tailed brachycephalic dogs. Neurologically normal dogs underwent CT for reasons unrelated to spinal disease, while affected dogs underwent MRI. Imaging studies were reviewed and vertebral malformations including hemivertebrae, block vertebrae, transitional vertebrae, and spina bifida were documented.The group of clinically normal dogs consisted of 62 French bulldogs, 68 Pugs and 41 English bulldogs. The group of affected dogs consisted of one French bulldog and nine Pugs. Overall, 80.7% of neurologically normal animals were affected by at least one vertebral malformation. There was a significant influence of breed, with thoracic vertebral malformations occurring more often in neurologically normal French bulldogs (P < 0.0001) and English bulldogs (P = 0.002). Compared to other breeds, hemivertebrae occurred more often in neurologically normal French bulldogs (93.5%; P < 0.0001 vs. Pugs; P = 0.004 vs. English bulldogs) and less often in neurologically normal Pugs (17.6%; P = 0.004 vs. English bulldogs). Neurologically normal Pugs were more often diagnosed with transitional vertebrae and spina bifida compared to other breeds (P < 0.0001 for both malformations). Of Pugs included in the study, 4.7% were diagnosed with clinically relevant thoracic vertebral malformations. When compared to the general veterinary hospital population, this was significantly more than the other two breeds (P = 0.006). This study indicates that thoracic vertebral malformations occur commonly in neurologically normal screw-tailed brachycephalic dogs. While hemivertebrae are often interpreted as incidental diagnostic findings, they appear to be of greater clinical importance in Pugs compared to other screw-tailed brachycephalic breeds.

Computer-assisted radiographic calculation of spinal curvature in brachycephalic "screw-tailed" dog breeds with congenital thoracic vertebral malformations: reliability and clinical evaluation.

The objectives of this study were: To investigate computer-assisted digital radiographic measurement of Cobb angles in dogs with congenital thoracic vertebral malformations, to determine its intra- and inter-observer reliability and its association with the presence of neurological deficits. Medical records were reviewed (2009–2013) to identify brachycephalic screw-tailed dog breeds with radiographic studies of the thoracic vertebral column and with at least one vertebral malformation present. Twenty-eight dogs were included in the study. The end vertebrae were defined as the cranial end plate of the vertebra cranial to the malformed vertebra and the caudal end plate of the vertebra caudal to the malformed vertebra. Three observers performed the measurements twice. Intraclass correlation coefficients were used to calculate the intra- and inter-observer reliabilities. The intraclass correlation coefficient was excellent for all intra- and inter-observer measurements using this method. There was a significant difference in the kyphotic Cobb angle between dogs with and without associated neurological deficits. The majority of dogs with neurological deficits had a kyphotic Cobb angle higher than 35°. No significant difference in the scoliotic Cobb angle was observed. We concluded that the computer assisted digital radiographic measurement of the Cobb angle for kyphosis and scoliosis is a valid, reproducible and reliable method to quantify the degree of spinal curvature in brachycephalic screw-tailed dog breeds with congenital thoracic vertebral malformations.

Hindlimb paresis associated with kyphosis, hemivertebrae and multiple thoracic vertebral malformations in a Quarter Horse gelding

Hindlimb paresis associated with kyphosis, hemivertebrae and multiple thoracic vertebral malformations in a Quarter Horse gelding

A Missense T(Brachyury) Mutation Contributes to Vertebral Malformations

No major susceptibility genes for sporadically occurring congenital vertebral malformations (CVM) in humans have been identified to date. Body patterning genes whose mutants cause axial skeletal anomalies in mice are candidates for human CVM susceptibility. T (also known as Brachyury) and TBX6 are critical genes needed to establish mesodermal identity. We hypothesized that mutations in T and/or TBX6 contribute to the pathogenesis of human CVMs. The complete T and TBX6 coding regions, splice junctions, and proximal 500 bp of the promoters were sequenced in 50 phenotyped patients with CVM. Three unrelated patients with sacral agenesis, Klippel-Feil syndrome, and multiple cervical and thoracic vertebral malformations were heterozygous for a c.1013C>T substitution, resulting in a predicted Ala338Val missense alteration in exon 8. A clinically unaffected parent of each patient also harbored the substitution, but the variant did not occur in an ethnically diverse, 443-person reference population. The c.1013C>T variant is significantly associated with CVM (p < 0.001). Alanine 338 shows moderate conservation across species, and valine at this position has not been reported in any species. A fourth patient harbored a c.908-8C>T variant in intron 7. This previously unreported variant was tested in 347 normal control subjects, and 11 heterozygotes and 2 T/T individuals were found. No TBX6 variants were identified. We infer that the c.1013C>T substitution is pathogenic and represents the first report of an association between a missense mutation in the T gene and the occurrence of sporadic CVMs in humans. It is uncertain whether the splice junction variant increases CVM risk. TBX6 mutations do not seem to be associated with CVM. We hypothesize that epistatic interactions between T and other developmental genes and the environment modulate the phenotypic consequences of T variants.

An analysis of PAX1 in the development of vertebral malformations

An analysis of PAX1 in the development of vertebral malformations. Due to the sporadic occurrence of congenital vertebral malformations, traditional linkage approaches to identify genes associated with human vertebral development are not possible. We therefore identified PAX1 as a candidate gene in vertebral malformations and congenital scoliosis due to its mutation in the undulated mouse. We performed DNA sequence analysis of the PAX1 gene in a series of 48 patients with congenital vertebral malformations, collectively spanning the entire vertebral column length. DNA sequence coding variants were identified in the heterozygous state in exon 4 in two male patients with thoracic vertebral malformations. One patient had T9 hypoplasia, T12 hemivertebrae and absent T10 pedicle, incomplete fusion of T7 posterior elements, ventricular septal defect, and polydactyly. This patient had a CCC (Pro)-->CTC (Leu) change at amino acid 410. This variant was not observed in 180 chromosomes tested in the National Institute of Environmental Health Sciences (NIEHS) single nucleotide polymorphism (SNP) database and occurred at a frequency of 0.3% in a diversity panel of 1066 human samples. The second patient had a T11 wedge vertebra and a missense mutation at amino acid 413 corresponding to CCA (Pro)-->CTA (Leu). This particular variant has been reported to occur in one of 164 chromosomes in the NIEHS SNP database and was found to occur with a similar frequency of 0.8% in a diversity panel of 1066 human samples. Although each patient's mother was clinically asymptomatic and heterozygous for the respective variant allele, the possibility that these sequence variants have clinical significance is not excluded.

Axial skeletal malformations induced by acetazolamide in rabbits.

In order to evaluate the teratogenic potential of acetazolamide in rabbits, three groups of 18 artificially inseminated females were treated orally with 50, 100, or 150 mg/kg/day of acetazolamide on days 6-18 of gestation. These doses induced maternal acidosis and electrolyte changes, consistent with those reported in rats and considered to be a result of carbonic anhydrase inhibition, as well as reductions in maternal body weight gain. At cesarean sections, average fetal body weights in the acetazolamide groups were dose-dependently decreased compared with controls. There were no effects of acetazolamide on embryonic survival or external morphology of live fetuses. In the fetal skeletal examination, thoracic and lumbar vertebral malformations occurred in 0.7%, 3.9%, and 6.1% of fetuses in the 50, 100, and 150 mg/kg/day groups, respectively, compared with none in the control group. In addition, missing vertebra was seen in a small number of fetuses in the 100 and 150 mg/kg/day groups. These axial skeletal malformations were, in some cases, associated with costal malformations. These results indicate that acetazolamide at maternotoxic doses can produce axial skeletal malformations in the rabbit.