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Introduction: Intervertebral disc protrusion (IVDP) is a neurological disorder commonly observed at the lumbosacral junction of old, medium-to-large breeds, non-chondrodystrophic dogs. Although uncommon, lumbosacral IVDP can also be seen in chondrodystrophic dogs, among them French Bulldogs (FBs) and could be associated with congenital vertebral malformations in this breed. This study aims to evaluate the prevalence, clinical features, and MRI characteristics of lumbosacral IVDP and congenital vertebral malformations in FBs diagnosed with thoracic or lumbar intervertebral disc extrusion (IVDE) and to evaluate the possible interference of the neurologic deficits related to chronic IVDP on neurological examination. Materials and methods: This is a single-center, retrospective case series. A search for FBs diagnosed with IVDE affecting the thoracic or lumbar regions is done on the database of the AniCura I Portoni Rossi Veterinary Hospital (Zola Predosa, Bologna, Italy). Eligible dogs have a complete medical report and a high-field MRI of the lumbosacral junction. MRIs of the lumbosacral junction are evaluated to determine the position of IVDP, cranial intervertebral foraminal stenosis, and signs of nerve root involvement. Radiographs, when available, are reviewed to identify the presence of lumbosacral congenital vertebral malformations. Results: Eighty FBs are included in the study. The prevalence of lumbosacral IVDP among FBs is 91.3%. Among FBs with lumbosacral IVDP, 45.0% show concurrent cranial intervertebral foraminal stenosis, 28.8% exhibit concurrent nerve root involvement, 56.2% appear to be asymptomatic for lumbosacral changes, while 15.1% manifest a decreased or absent withdrawal reflex as a supposed consequence of chronic lumbosacral IVDP. Congenital vertebral malformations are detected in 10 dogs. Conclusion: The results of this study support the hypothesis that lumbosacral IVDP is frequent in FBs presenting with thoracic or lumbar IVDE. In over half the dogs lumbosacral IVDP appears to be asymptomatic; however, in other cases, chronic lumbosacral IVDP seems to cause neurological deficits that may lead to erroneous localization of acute IVDE, representing a confounding factor for clinicians.
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OBJECTIVE: The genetic variations contributed to a substantial proportion of congenital vertebral malformations (CVM). SOX9 gene, a member of the SOX gene family, has been implicated in CVM. To study the SOX9 mutation in CVM patients is of great significance to explain the pathogenesis of scoliosis (the clinical manifestation of CVM) and to explore the pathogenesis of SOX9-related skeletal deformities. METHODS: A total of 50 singleton patients with CVM were included in this study. Exome Sequencing (ES) was performed on all the patients. The recurrent candidate variant of SOX9 gene was validated by Sanger sequencing. Luciferase assay was performed to investigate the functional changes of this variant. RESULTS: A recurrent rare heterozygous missense variant in SOX9 gene (NM_000346.3: c.1405A>G, p.M469V) which had not been reported previously was identified in three CVM patients who had the clinical findings of congenital scoliosis without deformities in other systems. This variant was absent from our in-house database and it was predicted to be deleterious (CADD = 24.5). The luciferase assay demonstrated that transactivation capacity of the mutated SOX9 protein was significantly lower than that of the wild-type for the two luciferase reporters (p = 0.0202, p = 0.0082, respectively). CONCLUSION: This SOX9 mutation (p.M469V) may contribute to CVM without other systematic deformity, which provides important implications and better understanding of phenotypic variability in SOX9-related skeletal deformities.
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Anomalías Congénitas/genética , Mutación Missense , Factor de Transcripción SOX9/genética , Enfermedades de la Columna Vertebral/genética , Columna Vertebral/anomalías , Adolescente , Niño , Preescolar , China/epidemiología , Anomalías Congénitas/epidemiología , Femenino , Heterocigoto , Humanos , Masculino , Pronóstico , Enfermedades de la Columna Vertebral/congénito , Enfermedades de la Columna Vertebral/epidemiología , Columna Vertebral/metabolismo , Columna Vertebral/patologíaRESUMEN
BACKGROUND: VACTERL association is a sporadic, nonrandom series of congenital malformations diagnosed by the presence of three or more of the following: vertebral malformations, anal atresia, cardiac defects, tracheoesophageal fistula, renal malformations, and limb malformations. Situs inversus totalis (SIT) and esophageal malformations are rarely associated. This is the first reported case in North America of VACTERL association with SIT. IMPLICATIONS FOR PRACTICE: Respiratory distress in the term infant requires full exploration of all possible causes because the etiology may be far more complex than routinely diagnosed respiratory distress syndrome. This particular case demonstrates physical exam findings and supportive imaging that would be observed in infants with VACTERL association and with SIT, highlighting considerations when, rarely, both occur simultaneously.
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Canal Anal/anomalías , Esófago/anomalías , Cardiopatías Congénitas , Riñón/anomalías , Deformidades Congénitas de las Extremidades , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Situs Inversus , Columna Vertebral/anomalías , Tráquea/anomalías , Cuidados Posteriores/métodos , Canal Anal/fisiopatología , Diagnóstico Diferencial , Esófago/fisiopatología , Femenino , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/fisiopatología , Cardiopatías Congénitas/terapia , Humanos , Recién Nacido , Riñón/fisiopatología , Deformidades Congénitas de las Extremidades/complicaciones , Deformidades Congénitas de las Extremidades/diagnóstico , Deformidades Congénitas de las Extremidades/fisiopatología , Deformidades Congénitas de las Extremidades/terapia , Tamizaje Neonatal/métodos , Manejo de Atención al Paciente/métodos , Examen Físico/métodos , Radiografía Abdominal/métodos , Radiografía Torácica/métodos , Situs Inversus/complicaciones , Situs Inversus/diagnóstico , Situs Inversus/fisiopatología , Situs Inversus/terapia , Columna Vertebral/fisiopatología , Tráquea/fisiopatología , Enfermedades del Nervio Vestibulococlear/congénito , Enfermedades del Nervio Vestibulococlear/diagnósticoRESUMEN
Musculocontractural Ehlers-Danlos syndrome caused by mutations in CHST14 (mcEDS-CHST14) is a recently delineated disorder, characterized by craniofacial, skeletal, visceral, and ocular malformations; and progressive cutaneous, skeletal, vascular, and visceral fragility-related manifestations. Spinal lesions, though one of the most serious complications, have not been investigated systematically. In this study, we report detailed and comprehensive information about spinal lesions of 12 patients with a mean age at the first visit of 13.4 years. Eight patients (66.7%) had scoliosis with a Cobb angle ≥10°, including one with severe scoliosis with a Cobb angle ≥45°. Five patients (41.7%) had kyphosis at the thoracolumbar junction with a kyphotic angle ≥20°. Three patients (25%) developed severe thoracolumbar kyphosis with a kyphotic angle ≥50° accompanied by thoracic lordosis with a wedge-like vertebral deformity and anterior vertebral osteophyte at the thoracolumbar junction, and two of them underwent surgical correction: complicated by fistula formation in one and performed safely and effectively through two-staged operation in the other. Six patients (50.0%) had cervical kyphosis, all of whom except one had kyphosis ≥20° at the thoracolumbar level. Two patients (16.7%) had atlantoaxial subluxation, and 10 patients (83.3%) had cervical vertebral malformations. Patients with mcEDS-CHST14 are susceptible to develop scoliosis, thoracolumbar kyphosis, and cervical kyphosis; and are recommended to have regular surveillance including total spine radiology. The present findings also suggest the critical role of dermatan sulfate in the development and maintenance of the spine.
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Síndrome de Ehlers-Danlos/enzimología , Médula Espinal/patología , Sulfotransferasas/deficiencia , Adolescente , Adulto , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Niño , Preescolar , Síndrome de Ehlers-Danlos/diagnóstico por imagen , Femenino , Humanos , Masculino , Médula Espinal/diagnóstico por imagen , Médula Espinal/cirugía , Sulfotransferasas/metabolismo , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
A variety of structural developmental anomalies affect the vertebral column. Malformed vertebrae can arise secondary to errors of vertebral formation, fusion and/or segmentation and developmental variation. Malformations can be simple with little or no clinical consequence, or complex with serious structural and neurologic implications. These anomalies can occasionally mimic acute trauma (bipartite atlas versus Jefferson fracture, butterfly vertebra versus burst fracture), or predispose the affected individual to myelopathy. Accurate imaging interpretation of vertebral malformations requires knowledge of ageappropriate normal, variant and abnormal vertebral morphology and the clinical implications of each entity. This knowledge will improve diagnostic confidence in acute situations and confounding clinical scenarios.This review article seeks to familiarize the reader with the embryology, normal and variant anatomy of the vertebral column and the imaging appearance and clinical impact of the spectrum of vertebral malformations arising as a consequence of disordered embryological development.Teaching points ⢠Some vertebral malformations predispose the affected individual to trauma or myelopathy. ⢠On imaging, malformed vertebrae can be indistinguishable from acute trauma. ⢠Abnormalities in spinal cord development may be associated and must be searched for. ⢠Accurate interpretation requires knowledge of normal, variant and abnormal vertebral morphology.
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Spondylocostal dysostosis (SCD) is a rare disorder characterized by vertebral segmentation defects and malformations of the ribs. SCD patients have some degree of (kypho)scoliosis, short stature and suffer from respiratory impairment due to the reduced size of their thoracic cage. Mutations in DLL3, MESP2, LFNG, HES7, TBX6, and RIPPLY2 are known to cause different subtypes of SCD. Here, we report on a male neonate with an apparent distinct SCD-like phenotype only partly overlapping the previously described SCD subtypes. The proband presented with severe rib malformations (missing, fused, bifid, and hypoplastic ribs), vertebral malformations (intervertebral fusions of the laminae and irregular ossification of the vertebral bodies), and a mild scoliosis. Clear segmentation defects of the vertebral bodies were lacking. Other dysmorphic features were present as well. Severe respiratory insufficiency was present from birth. Whole exome sequencing identified a homozygous start-loss variant in DMRT2 (NM_006557.6: c.1A > T p.[Met1?]) being a likely cause of the SCD-like phenotype in the proband. Mutations in DMRT2 (OMIM#604935) have not been described in relation to SCD-related phenotypes in humans before. However, Dmrt2 knock-out mice exhibit severe rib and vertebral defects that strikingly overlap with the radiological phenotype of the proband reported here. Therefore, it seems plausible that mutations in DMRT2 are associated with a different (novel) subtype of SCD mainly characterized by severe rib anomalies but lacking clear segmentation defects of the vertebral bodies.
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Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Proteínas de Unión al ADN/genética , Hernia Diafragmática/diagnóstico , Hernia Diafragmática/genética , Homocigoto , Mutación , Fenotipo , Costillas/anomalías , Columna Vertebral/anomalías , Factores de Transcripción/genética , Alelos , Resultado Fatal , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Recién Nacido , Masculino , Radiografía , Costillas/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada Espiral , Secuenciación del ExomaRESUMEN
Congenital vertebral malformations (CVM) occur in 1 in 1000 live births and in many cases can cause spinal deformities, such as scoliosis, and result in disability and distress of affected individuals. Many severe forms of the disease, such as spondylocostal dystostosis, are recessive monogenic traits affecting somitogenesis, however the etiologies of the majority of CVM cases remain undetermined. Here we demonstrate that morphological defects of the notochord in zebrafish can generate congenital-type spine defects. We characterize three recessive zebrafish leviathan/col8a1a mutant alleles ((m531, vu41, vu105)) that disrupt collagen type VIII alpha1a (col8a1a), and cause folding of the embryonic notochord and consequently adult vertebral column malformations. Furthermore, we provide evidence that a transient loss of col8a1a function or inhibition of Lysyl oxidases with drugs during embryogenesis was sufficient to generate vertebral fusions and scoliosis in the adult spine. Using periodic imaging of individual zebrafish, we correlate focal notochord defects of the embryo with vertebral malformations (VM) in the adult. Finally, we show that bends and kinks in the notochord can lead to aberrant apposition of osteoblasts normally confined to well-segmented areas of the developing vertebral bodies. Our results afford a novel mechanism for the formation of VM, independent of defects of somitogenesis, resulting from aberrant bone deposition at regions of misshapen notochord tissue.