A novel variant in the FLNB gene associated with spondylocarpotarsal synostosis syndrome.

OBJECTIVES: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan. METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant. RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before. CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.

Clinical outcomes of 20 brachycephalic dogs with thoracolumbar spinal deformities causing neurological signs treated with spinal stabilization using 3D-printed patient-specific drill guides.

OBJECTIVE: To describe the clinical outcomes for pugs and French bulldogs with congenital vertebral malformations, undergoing thoracolumbar spinal stabilization surgery using 3D-printed patient-specific drill guides. To evaluate the accuracy of pedicle screw placement in this group of dogs. STUDY DESIGN: Retrospective descriptive study. ANIMALS: Twenty dogs (12 pugs and eight French bulldogs). METHODS: Medical records searched between August 2018 and March 2021 for pugs and French bulldogs diagnosed with congenital vertebral abnormalities via magnetic resonance imaging (MRI) scan and computed tomography (CT) scan causing T3-L3 myelopathy signs that underwent spinal stabilization surgery using 3D-printed patient-specific drill guides followed by a postoperative CT scan. The short-term outcome was based on the neurological grade (modified Frankel score-MFS) on the day after surgery, day of discharge, and at the follow-up examination at 4 to 6 weeks after surgery. The mid-term outcome was obtained via an online questionnaire (or direct examination in one case). RESULTS: Twenty dogs met the inclusion criteria (19/20 grade 2 MFS, 1/20 grade 4 MFS). No complications were reported in the immediate postoperative period and optimal pedicle screw placement was obtained in 169/201 of screws. Twenty-four hours after surgery 16/20 dogs displayed an unchanged neurological grade. Short-term outcomes revealed a static (17/20) or improved (2/20) neurological grade. Ten owners participated in the online questionnaire. All patients were reported to be ambulatory; however, 7/10 dogs displayed abnormal gait. Neurological signs had remained static (6/10) or improved (3/10) in comparison with the dogs' preoperative status at a median of 883.5 days from the surgery. CONCLUSION: Dogs in this study had a favorable short-term outcome and mid-term outcome evaluation revealed a static/improved neurological status. CLINICAL SIGNIFICANCE: Thoracolumbar spinal stabilization surgery using 3D-printed patient-specific drill guides showed a favorable outcome in brachycephalic breeds affected by vertebral deformities.

Risks Associated with Surgical Management of Lumbosacral Transitional Vertebrae: Systematic Review of Surgical Considerations and Illustrative Case.

BACKGROUND: Lumbosacral transitional vertebrae (LSTV) are congenital anomalies of the L5-S1 segments characterized by either sacralization of the most caudal lumbar vertebra or lumbarization of the most cephalad sacral vertebra. This variation in anatomy exposes patients to additional surgical risks. METHODS: In order to shed light on surgical considerations reported for lumbar spine cases involving LSTV as described in the extant literature, we performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We also present a case example in which wrong level surgery was avoided due to anatomical understanding of LSTV. RESULTS: A 48-year-old female presented with severe back pain after sustaining a fall from ten feet. The patient exhibited full motor function in all extremities but had begun to experience urinary retention. On initial imaging read, the patient was suspected to have an L1 burst fracture. A review of the imaging demonstrated a transitional vertebra. Therefore, based on the last rib corresponding to T12, the fractured level was L2. This case illustrates the risk LSTV carries for wrong site surgery; appropriate levels were then decompressed and instrumented. On systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a three database literature search identified 39 studies describing 885 patients with LSTV and relevant surgical considerations. The primary indications for surgery were for disc herniation (37%), Bertolotti's syndrome (35%), and spinal stenosis (25%). This cohort displayed a mean follow-up time of 23 months. Reherniation occurred in 12 patients (5.5%). Medical management through steroid injection was 24, 72% (n = 80) for the sample. Wrong level surgery occurred in 1.4% (n = 12) of patients. CONCLUSIONS: LSTV represents a constellation of changes in anatomy beyond just a sacralized or lumbarized vertebra. These anatomical differences expose the patient to additional surgical risks. This case and review of the literature highlight avoidable complications and in particular wrong level surgery.

Congenital Stenosis of the Spine-A Cross-Sectional Study of 1019 Whole-Spine Computed Tomography Scans to Determine Prevalence and Association Among Multilevel, Tandem, and Triple Region Stenosis.

BACKGOUND: Patients with congenital stenosis of the spine (CSS) present with clinical symptoms at an early age and fewer degenerative hypertrophic changes than the more common degenerative cohort. Literature is lacking in the true prevalence of CSS affecting the 3 segments of the spine in isolation, as well as in tandem in the Indian subcontinent. METHODS: Anteroposterior spinal canal diameter in axial plane computed tomography at the midvertebral level was measured in asymptomatic patients with whole-spine computed tomography. Spinal canal stenosis was defined as a diameter of <12 mm for the cervical region, <12 mm for the thoracic region, and <13 mm for the lumbar region. Single-level and multilevel stenosis, as well as tandem and triple-region stenosis, were evaluated. RESULTS: The results show the prevalence of CSS as 16.6%, 11.5%, and 20.1% involving the cervical, thoracic, and lumbar spine, respectively. Single-level stenosis affected 90.6%, 94%, and 79.8% of the patients with cervical, thoracic, and lumbar CSS, respectively. Tandem stenosis affected 10.4% of the population (n = 104), with cervicolumbar stenosis being the most prevalent (n = 51, 5%). The presence of CSS in any one segment of the spine was significantly associated with the presence of stenosis at one of the other segments (P < 0.05). Triple-region stenosis was seen in 0.3% (n = 3) patients. CONCLUSIONS: The prevalence of cervical, thoracic, lumbar and tandem stenosis from our study is established at 16.6%, 11.5%, 20.1%, and 10.4%. Additionally, our study demonstrates the association between stenosis of the different regions of the spine.

Lumbosacral transitional vertebra in 14 dog breeds in Norway: Occurrence, risk factors and association with hip dysplasia.

A lumbosacral transitional vertebra (LTV) is a congenital anomaly of the spine and has been suggested to predispose to canine hip dysplasia (CHD). This retrospective, cross-sectional study investigated the prevalence of LTV and CHD among 14 dog breeds in Norway, the possible associations with risk factors, and whether LTV was a risk factor for the development of hip dysplasia. The results were based on evaluation of ventrodorsal radiographs from the CHD screening program from the Norwegian Kennel Club from February 2014 to January 2022. A total of 13,950 dogs were included in the study. For statistical analysis, CHD grades were reclassified from the official Federation Cynologique Internationale (FCI) grades into three grades: CHD free (CHD=A, B), CHD mild (CHD=C), and CHD severe (CHD=D, E). In the study sample, the overall occurrence of LTV was 18.5%, of which 32.9% were type 1, 45.7% type 2% and 21.4% type 3. The occurrence of LTV varied significantly among the included breeds, ranging from 9.5% to 46.2%. There was no association between sex and LTV. The frequencies of CHD grades were A: 43.1%; B: 31.4%; C: 18.4%; D: 6.0%; E: 1.1%. There was a statistically significant association with mild and severe CHD in dogs with LTV type 2 and LTV type 3 (P< 0.001). In the population studied, the prevalence of LTV was different among breeds. This supports initial data on the heredity of LTV and the diverse occurrence of LTV among breeds. Our results indicate that LTV type 2 and type 3 are associated with mild and severe CHD development. Therefore, this study has potentially identified an additional risk factor for the development of hip dysplasia.

Medium-term and Long-term Follow-up Surgical Outcomes of the 1-stage Posterior-only Lumbosacral Hemivertebra Resection With Short-segment Fusion in Children.

BACKGROUND: The objective of this study was to evaluate the medium-term and long-term surgical outcomes of the 1-stage posterior-only lumbosacral hemivertebra resection with short-segment fusion in children. METHODS: This retrospective chart review included 21 children with congenital scoliosis due to lumbosacral hemivertebra who received 1-stage posterior-only hemivertebra resection with short-segment fusion from 2012 to 2016 with at least 5 years of follow-up. Standing anteroposterior and lateral radiographs of the spine were compared preoperatively, postoperatively, and at last follow-up. Radiographic evaluation included measured changes in segmental scoliosis and lordosis, compensatory scoliosis, thoracic kyphosis, lumbar lordosis, trunk shift, and sagittal spinopelvic alignment. RESULTS: There were 12 boys and 9 girls with a mean age of 6.5±3.2 years. The mean follow-up period was 6.7±1.3 years. The mean fusion level was 2.7±0.9 segments. The mean segmental scoliosis was 29±6 degrees preoperatively, 9±3 degrees (correction rate of 71%) postoperatively ( P <0.05), and 7±3 degrees (correction rate of 76%) at the latest follow-up. The compensatory curve of 26±12 degrees was spontaneously corrected to 14±8 degrees (correction rate of 47%) at last follow-up ( P <0.05). Trunk shift was significantly improved on both coronal (53%) and sagittal (56%) planes after surgery ( P 0.05) and stable at follow-up. The sagittal spinopelvic alignment was balanced in all cases. There were no neurological or infectious complications. CONCLUSIONS: It is safe and effective to perform 1-stage posterior-only lumbosacral hemivertebra resection with short-segment fusion, which can significantly correct the segmental scoliosis, prevent the compensatory curve progress and improve the trunk shift. This strategy also can save motion segments and avoid long lumbar fusion. Medium-term and long-term follow-up outcomes are satisfactory. LEVEL OF EVIDENCE: Level III.

Lumbosacral transitional vertebrae: prevalence in a southern European population and its association with low back pain.

PURPOSE: Lumbosacral transitional vertebra (LSTV) is a congenital anomaly of the lumbosacral junction. Its prevalence is variable in the literature such as its association with low back pain. The aim of this study was to identify the prevalence of LSTV in a southern European population, and its correlation with low back pain. METHODS: A retrospective review of 639 thoraco-abdomino-pelvic consecutive CT-scans between January 2019 and November 2020 was performed. The presence of LSTV was classified into type II, III, IV based on Castellvi's classification. To investigate the association with low back pain, Oswestry Low Back Disability Questionnaire (ODI) and the EuroQol-5D-3L questionnaire was applied. RESULTS: The prevalence of LSTV was 24.9% (142 of 571). 37,3% were type IIb, 31,0% were type IIa, 13,4% were type IIIa, 9.9% were type IIIb and 8.5% were type IV. Individuals with LSTV were more likely to report low back pain and have a higher ODI score (OR:0.392, 95% CI:0.192-0.802, p = 0.010), (OR: 1050, 95% CI: 1029-1072, p < 0.01). Castellvi's type IV showed a significantly higher ODI when compared to type II (OR:1059, 95% CI:1019-1100, p = 0,04). There was no statistical difference in the EuroQol-5D-3L score between two groups (OR:1085, 95% CI: 0.459-2.560, p = 0.852). CONCLUSION: This population-based study adds to the literature the prevalence of LSTV in a southern European population. LSTV was associated with low back pain. However, this difference did not translate into a loss of quality life. Type IV was associated with higher functional disability when compared with type II.

Thoracolumbar stenosis and neurologic symptoms: Quantitative MRI in achondroplasia.

BACKGROUND AND PURPOSE: Whole-spine magnetic resonance imaging (MRI) studies, to identify structural abnormalities associated with the development of symptomatic spinal stenosis in achondroplasia. METHODS: Forty-two subjects with achondroplasia were grouped into four age-related categories. Congenital spinal deformities (vertebral body and disc height, interpedicular distance), acquired spinal degenerative changes, thoracic kyphotic (TK) angle, thoracolumbar kyphotic (TLK) angle, spinal canal widths were evaluated by MRI. RESULTS: Patients in the first three groups were asymptomatic and younger (group 1: 4.4 ± 0.78 years; group 2: 8.18 ± 0.60 years; group 3: 10.95 ± 0.93 years) than the symptomatic group (group 4: 23 ± 1.30 years). Patients showed height of vertebral bodies, whole canal width, and average lumbar interpedicular distance reduced. Discs degeneration was more pronounced in the lumbar region and in symptomatic adult patients. TK and TLK angles showed a positive correlation with age (p < .05, r = .42; p < .05, r = .41), whereas thoracic and thoracolumbar canal width had a negative correlation (p < .05, r = -.69; p < .05, r = -.58). A negative correlation between lumbar discs degeneration and canal width was found only at L1-L3 level (p < .05, r = -.35). At L1-L3, the canal width cutoff value of .59 allowed the differentiation between asymptomatic and symptomatic patients (area under the curve of .966, p < .0001). CONCLUSION: In achondroplasia, the spinal canal narrowing, due to accelerated degenerative changes, is a predisposing factor of symptomatic lumbar spinal stenosis. Lumbar canal MRI is a helpful tool to detect the risk of the development of neurological symptoms; in adult patients, a stenosis higher than 60% of upper lumbar canal could be a critical value for the onset of neurological symptoms.

Bi-allelic MYH3 loss-of-function variants cause a lethal form of contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B.

Arthrogryposis is a consequence of reduced fetal movements and arises due to environmental factors or underlying genetic defects, with extensive genetic heterogeneity. In many instances, the genes responsible are involved in neuromuscular function. Missense variants in the gene encoding embryonic myosin heavy chain (MYH3) usually cause distal arthrogryposis. Recently, mono-allelic or bi-allelic MYH3 variants have been associated with contractures, pterygia, and spondylocarpotarsal fusion syndrome 1 (CPSFS1A and CPSFS1B). Here we describe three fetuses presenting in the second trimester with a lethal form of arthrogryposis and pterygia and harbouring bi-allelic variants in MYH3. One proband was compound heterozygous for a missense change and an extended splice site variant, a second proband had a homozygous frameshift variant, and a third proband was homozygous for a nonsense variant. Minigene assays performed on the first fetus showed that the missense and extended splice site variants resulted in aberrant splicing, likely resulting in near complete loss of full-length MYH3 transcript. This study shows that loss of MYH3 is associated with a lethal arthrogryposis phenotype and highlights the utility of minigene assays to assess splicing.

Association of spinal anomalies with spondylolysis and spina bifida occulta.

PURPOSE: To investigate the association of spinal anomalies with lumbar spondylolysis and spina bifida occulta (SBO). METHODS: A total of 1190 patients with thoracic, abdominal, and pelvic computed tomography scans available were categorized according to the number of presacral (thoracic and lumbar) mobile vertebrae and the presence or absence of lumbosacral transitional vertebrae (LSTV). The prevalence of spondylolysis and SBO and the association of spinal anomalies with these disorders were evaluated. RESULTS: Normal morphology (17 mobile vertebra with no LSTV) was found in 607 men (86.5%) and 419 women (85.9%) and about 14% of patients had anomalies. Spondylolysis was found in 74 patients (6.2%), comprising 54 men (7.7%) and 20 women (4.1%). SBO involving the lumbar spine was found in 9 men (1.3%) and 2 women (0.4%). Spondylolysis was significantly more common in men with 18 vertebrae without LSTV (21.1%) than in those with 17 vertebrae without LSTV (7.2%) (p = 0.002). The prevalence of spinal anomalies was 55.6% in men and 50.0% in women with SBO that included a lumbar level was significantly higher than in both men (13.5%, p < 0.001) and women (4.8%, p = 0.003) without SBO. CONCLUSION: These findings indicate that there is a relationship between spinal anomalies and both spondylolysis and SBO, which may lead to elucidation of the mechanism of onset of spondylolysis and improve its treatment and prognosis. Awareness that patients with SBO involving the lumbar spine have an increased likelihood of a spinal anomaly may help to prevent level errors during spinal surgery.

Bioinformatics Analysis and Experimental Verification Identify Downregulation of COL27A1 in Poor Segmental Congenital Scoliosis.

BACKGROUND: Congenital scoliosis (CS) represents the congenital defect disease, and poor segmental congenital scoliosis (PSCS) represents one of its types. Delayed intervention can result in disability and paralysis. In this study, we would identify the core biomarkers for PSCS progression through bioinformatics analysis combined with experimental verification. METHODS: This work obtained the GSE11854 expression dataset associated with somite formation in the GEO database, which covers data of 13 samples. Thereafter, we utilized the edgeR of the R package to obtain DEGs in this dataset. Then, GO annotation, KEGG analyses, and DO annotation of DEGs were performed by "clusterProfiler" of the R package. This study performed LASSO regression for screening the optimal predicting factors for somite formation. Through RNA sequencing based on peripheral blood samples from healthy donors and PSCS cases, we obtained the RNA expression patterns and screen out DEGs using the R package DESeq2. The present work analyzed COL27A1 expression in PSCS patients by the RT-PCR assay. RESULTS: A total of 443 genes from the GSE11854 dataset were identified as DEGs, which were involved in BP associated with DNA replication, CC associated with chromosomal region, and MF associated with ATPase activity. These DEGs were primarily enriched in the TGF-ß signaling pathway and spinal deformity. Further, LASSO regression suggested that 9 DEGs acted as the signature markers for somite formation. We discovered altogether 162 DEGs in PSCS patients, which were involved in BP associated with cardiac myofibril assembly and MF associated with structural constituent of muscle. However, these 162 DEGs were not significantly correlated with any pathways. Finally, COL27A1 was identified as the only intersected gene between the best predictors for somite formation and PSCS-related DEGs, which was significantly downregulated in PSCS patients. CONCLUSION: This work sheds novel lights on DEGs related to the PSCS pathogenic mechanism, and COL27A1 is the possible therapeutic target for PSCS. Findings in this work may contribute to developing therapeutic strategies for PSCS.

A novel minimally invasive technique of inter-spinal distraction fusion surgery for single-level lumbar spinal stenosis in octogenarians: a retrospective cohort study.

OBJECTIVE: Surgical treatment of lumbar spinal stenosis (LSS) in octogenarians (patients aged ≥ 80 years) has been a challenge. Inter-spinal distraction fusion (ISDF)-a minimally invasive procedure-was used for treating LSS in octogenarians. This retrospective cohort study aimed to investigate the clinical efficacy and safety of a minimally invasive ISDF technique for LSS in octogenarian patients. METHODS: From April 2015 to April 2019, octogenarian patients who underwent lumbar fusion surgery due to single-segment LSS were included. The patients were grouped into the ISDF group and posterior lumbar interbody fusion (PLIF) group based on the type of surgery. Clinical outcomes were evaluated using scores of the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedics Association (JOA) scale. Radiographs were assessed for the intervertebral angle (IA), lumbar lordosis (LL), and posterior disc height (PDH). After 2 years postoperatively, all patients underwent computed tomography (CT) to evaluate the fusion condition. Perioperative data and related complications were recorded. RESULTS: Sixty-two patients were included (mean age: 82.22 ± 1.95 years). The ISDF and the PLIF groups had 34 and 28 patients, respectively. The average follow-up time was 2.1 ± 0.25 years. There was no significant difference in VAS, ODI, JOA, and PDH scores between both groups preoperatively and at each postoperative time-point. The IA and LL showed significant differences between both groups after surgery (p < 0.05). The postoperative IA in the ISDF group were significantly lower than the preoperative values, while that in the PLIF group were markedly increased. The PLIF group had an increased LL compared with that preoperatively (p < 0.05), while the LL in the ISDF did not significantly change. The operative time, blood loss, hospital stay time, and the rate of perioperative complications of the ISDF group were significantly lower than those of the PLIF group (p < 0.05). There was no significant difference in the fusion rates between both groups. CONCLUSION: ISDF surgery is a viable method for octogenarian patients with LSS that provides a similar clinical efficacy, shorter operative time, less blood loss, shorter hospital stay time, and fewer complications, compared to the PLIF surgery.

Anterior longitudinal ligament release from a posterior approach: an alternative to three-column osteotomy.

PURPOSE: Expansion of the anterior column and compression of the posterior column restores lordosis and sagittal imbalance. Anterior longitudinal ligament (ALL) release has been described from lateral and anterior approaches as a technique to improve lumbar lordosis; however, posterior approach to release the ALL has not been adequately assessed. METHODS: We demonstrate a case series of ALL release using a posterior approach performed in conjunction with posterior column osteotomy (PCO), with or without transforaminal lumbar interbody fusion (TLIF) for spinal deformity. Eleven cases were identified from billing records between 2010 and 2019. Retrospective review was conducted for perioperative complications and revision surgery. Overall and segmental lumbar lordosis (LL) correction was measured from pre- and postoperative imaging. RESULTS: Eleven patients underwent ALL release with a PCO. Kyphosis, scoliosis, and flat back syndrome were the most common spinal deformities. On average, patients had 9 ± 3 levels fused and a single level ALL release. ALL release was most commonly performed at L1-L2 and L2-L3 levels. An overall LL correction of 28.6° ± 19.8o was achieved; ALL release introduced 16.7° ± 11.9° of lordotic correction and accounted for 49.2 ± 30.4% of the overall lordotic correction. Average blood loss was 1030 ± 573 mL. CONCLUSIONS: ALL release as an adjunct to PCO and TLIF is a viable technique for providing increased deformity correction without subjecting the patient to a more invasive three-column osteotomy. While this approach may not be appropriate for all patients, it represents a useful option in spinal deformity correction while limiting blood loss and additional anterior surgery. LEVEL OF EVIDENCE: IV.

Efficacy and radiographic analysis of oblique lumbar interbody fusion in treating adult spinal deformity.

Adult spinal deformity (ASD) is usually rigid and requires a combined anterior-posterior approach for deformity correction. Anterior lumbar interbody fusion (ALIF) allows direct access to the disc space and placement of a large interbody graft. A larger interbody graft facilitates correction of ASD. However, an anterior approach carries significant risks. Lateral lumbar interbody fusion (LLIF) through a minimally invasive approach has recently been used for ASD. The present study was performed to evaluate the effectiveness of oblique lumbar interbody fusion (OLIF) in the treatment of ASD. We performed a retrospective study utilizing the data of 74 patients with ASD. The inclusion criteria were lumbar coronal Cobb angle > 20°, pelvic incidence (PI)-lumbar lordosis (LL) mismatch > 10°, and minimum follow-up of 2 years. Patients were divided into two groups: ALIF combined with posterior spinal fixation (ALIF+PSF) (n = 38) and OLIF combined with posterior spinal fixation (OLIF+PSF) (n = 36). The perioperative spinal deformity radiographic parameters, complications, and health-related quality of life (HRQoL) outcomes were assessed and compared between the two groups. The preoperative sagittal vertical axis (SVA), LL, PI-LL mismatch, and lumbar Cobb angles were similar between the two groups. Patients in the OLIF+PSF group had a slightly higher mean number of interbody fusion levels than those in the ALIF+PSF group. At the final follow-up, all radiographic parameters and HRQoL scores were similar between the two groups. However, the rates of perioperative complications were higher in the ALIF+PSF than OLIF+PSF group. The ALIF+PSF and OLIF+PSF groups showed similar radiographic and HRQoL outcomes. These observations suggest that OLIF is a safe and reliable surgical treatment option for ASD.

Transitional vertebrae and numerical variants of the spine : prevalence and relationship to low back pain or degenerative spondylolisthesis.

AIMS: Although lumbosacral transitional vertebrae (LSTV) are well-documented, few large-scale studies have investigated thoracolumbar transitional vertebrae (TLTV) and spinal numerical variants. This study sought to establish the prevalence of numerical variants and to evaluate their relationship with clinical problems. METHODS: A total of 1,179 patients who had undergone thoracic, abdominal, and pelvic CT scanning were divided into groups according to the number of thoracic and lumbar vertebrae, and the presence or absence of TLTV or LSTV. The prevalence of spinal anomalies was noted. The relationship of spinal anomalies to clinical symptoms (low back pain, Japanese Orthopaedic Association score, Roland-Morris Disability Questionnaire) and degenerative spondylolisthesis (DS) was also investigated. RESULTS: Normal vertebral morphology (12 thoracic and five lumbar vertebrae without TLTV and LSTV) was present in 531 male (76.7%) and 369 female patients (75.8%). Thoracolumbar transitional vertebrae were present in 15.8% of males and 16.0% of females. LSTV were present in 7.1% of males and 9.0% of females. The prevalence of the anomaly of 16 presacral mobile vertebrae (total number of thoracolumbar vertebrae and TLTV) without LSTV was 1.0% in males and 4.1% in females, and that of the anomaly of 18 vertebrae without LSTV was 5.3% in males and 1.2% in females. The prevalence of DS was significantly higher in females with a total of 16 vertebrae than in those with normal morphology. There was no significant correlation between a spinal anomaly and clinical symptoms. CONCLUSION: Overall, 24% of subjects had anomalies in the thoracolumbar region: the type of anomaly differed between males and females, which could have significant implications for spinal surgery. A decreased number of vertebrae was associated with DS: numerical variants may potentially be a clinical problem. Cite this article: Bone Joint J 2021;103-B(7):1301-1308.

Intragenic Deletions in FLNB Are Part of the Mutational Spectrum Causing Spondylocarpotarsal Synostosis Syndrome.

Spondylocarpotarsal synostosis syndrome (SCT) is characterized by vertebral fusions, a disproportionately short stature, and synostosis of carpal and tarsal bones. Pathogenic variants in FLNB, MYH3, and possibly in RFLNA, have been reported to be responsible for this condition. Here, we present two unrelated individuals presenting with features typical of SCT in which Sanger sequencing combined with whole genome sequencing identified novel, homozygous intragenic deletions in FLNB (c.1346-1372_1941+389del and c.3127-353_4223-1836del). Both deletions remove several consecutive exons and are predicted to result in a frameshift. To our knowledge, this is the first time that large structural variants in FLNB have been reported in SCT, and thus our findings add to the classes of variation that can lead to this disorder. These cases highlight the need for copy number sensitive methods to be utilized in order to be comprehensive in the search for a molecular diagnosis in individuals with a clinical diagnosis of SCT.

Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report.

BACKGROUND: Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height. CASE PRESENTATION: We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature. CONCLUSION: Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

Multi-level sagittally cleft vertebrae: a case report and review of the literature.

The term "sagittal cleft vertebra" (SCV) denotes a rare embryologically derived longitudinal defect within the vertebral body, which is clinically and radiologically challenging to diagnose in isolation. This defect results in two hemivertebrae, which ossify discordantly, ultimately leading to a sagittal cleft through the vertebral body. Often presenting with low back pain or concomitant with an associated syndromic illness, SCV is often found incidentally and can mimic vertebral compression fractures radiographically. Treatment of SCV has largely been conservative and symptomatic. With only 109 reported cases in the current literature, we present a unique case of multiple SCV throughout the thoracolumbar region in an adolescent patient. We performed a review of the literature to identify published cases of SCV to date. We searched PUBMED using the terms "sagittal cleft vertebrae", "butterfly vertebrae", and "anterior rachischisis". Abstracts were screened for reports specifically involving original cases of SCV. Given the well-established association with syndromic illnesses, finding an SCV warrants further investigation for other abnormalities of the musculoskeletal, cardiac, and genitourinary systems. Complex management strategies are rare unless the SCV is associated with an aberrant syndrome, disc herniation or severe musculoskeletal abnormality, or symptomatic disc herniation requiring surgical management. Further studies should focus on uncovering the genetic markers leading to the cleft vertebral bodies, with a focus on early screening and monitoring of patients who could be predisposed to the condition.

Clinical, MRI, and histopathological findings of congenital focal diplomyelia at the level of L4 in a female crossbred calf.

BACKGROUND: This case report describes the clinical signs of a calf with focal diplomyelia at the level of the fourth lumbar vertebra. Magnetic resonance imaging (MRI) images and histological findings of the affected spinal cord are included in this case report. This case differs from previously reported cases in terms of localization and minimal extent of the congenital anomaly, clinical symptoms and findings during further examinations. CASE PRESENTATION: The calf was presented to the Farm Animal Health clinic, Faculty of Veterinary Medicine, Utrecht University, with an abnormal, stiff, 'bunny-hop' gait of the pelvic limbs. Prominent clinical findings included general proprioceptive ataxia with paraparesis, pathological spinal reflexes of the pelvic limbs and pollakiuria. MRI revealed a focal dilated central canal, and mid-sagittal T2 hyperintense band in the dorsal part of the spinal cord at the level of the third to fourth lumbar vertebra. By means of histology, the calf was diagnosed with focal diplomyelia at the level of the fourth lumbar vertebra, a rare congenital malformation of the spinal cord. The calf tested positive for Schmallenberg virus antibodies, however this is not considered to be part of the pathogenesis of the diplomyelia. CONCLUSIONS: This case report adds value to future clinical practice, as it provides a clear description of focal diplomyelia as a previously unreported lesion and details its diagnosis using advanced imaging and histology. This type of lesion should be included in the differential diagnoses when a calf is presented with a general proprioceptive ataxia of the hind limbs. In particular, a 'bunny-hop' gait of the pelvic limbs is thought to be a specific clinical symptom of diplomyelia. This case report is of clinical and scientific importance as it demonstrates the possibility of a focal microscopic diplomyelia, which would not be evident by gross examination alone, as a cause of hind-limb ataxia. The aetiology of diplomyelia in calves remains unclear.