OBJECTIVE: To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. METHODS: A child diagnosed with 3MS type 1 at the Children's Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020). RESULTS: The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. WES revealed compound heterozygous variants in the CUL7 gene: c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child's father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c.2686G>T (p.E896) was classified as a pathogenic (PVS1+PM2_Supporting+PM3), and c.1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+PM2_Supporting). Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). CONCLUSION The compound heterozygous variants c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.
Humans ; Cullin Proteins/genetics* ; Female ; Child ; Limb Deformities, Congenital/genetics* ; Exome Sequencing ; Mutation ; Child, Preschool ; Dwarfism ; Muscle Hypotonia ; Spine/abnormalities*

OBJECTIVE: To analyze the clinical features and molecular genetic etiology of a patient with 3-M (Miller McKusick Malvaux) syndrome from a consanguineous parentage family, and to explore the relationship between genotype and phenotype. METHODS: After the consent of the proband's guardian and the informed consent form was signed, DNA was extracted from peripheral blood samples of the proband and her parents for chromosome microarray analysis, medical exome sequencing and parental verification. RESULTS: A total of 247.1 Mb loss of heterozygosity was found in the proband with a CytoScan 750K array. Furthermore, a homozygous variant (c.458dupG) of the OBSL1 gene was found using high-throughput sequencing, which was inherited from her parents. Based on the criteria and guidelines of genetic variation of American College of Medical Genetics and Genomics, the variant is predicted to be pathogenic (PVS1+PM2+PP4), and only one case was reported previously. CONCLUSION Spina bifida occulta and lower eyelid fat pad may be a special phenotype of c.458dupG variant of the OBSL1 gene. Our study may provide a useful reference for evaluating the relationship between genotype and phenotype of 3-M syndrome type 2.
Cytoskeletal Proteins ; Dwarfism ; Female ; Genomics ; Humans ; Molecular Biology ; Muscle Hypotonia ; Mutation ; Pedigree ; Spine/abnormalities* ; Whole Exome Sequencing

We report 13 children fulfilling criteria of Alagille syndrome. All had chronic cholestasis secondary to paucity of intrahepatic bile ducts and triangular facies. Eight children had associated congenital heart disease (six pulmonic stenosis, one each tetralogy of Fallot and patent ductus arteriosus), seven with butterfly vertebrae and one with posterior embryotoxon. Seven of the 13 children are alive and jaundice-free but three with concomitant hypercholesterolemia; the six other children died of liver-related complications.
Butterflies ; Bile Ducts, Intrahepatic ; Jaundice ; Musculoskeletal Abnormalities ; Spine

Cervical kyphosis is a rare condition that can cause significant functional disability and myelopathy. Deciding the appropriate treatment for such deformities is challenging for the surgeon. Patients often present with axial neck pain, and it is not uncommon to find coexisting radiculopathy or myelopathy. The optimal approach for addressing this complex issue remains controversial. A comprehensive surgical plan based on knowledge of the pathology and biomechanics is important for kyphosis correction. Here we reviewed diagnoses of the cervical spine along with the literature pertaining to various approaches and management of cervical spine.
Congenital Abnormalities ; Diagnosis ; Humans ; Kyphosis ; Neck Pain ; Pathology ; Radiculopathy ; Spinal Cord Diseases ; Spine

STUDY DESIGN: To induce scoliosis in young female Wistar rats using a noninvasive method and to validate this model. PURPOSE: To induce scoliosis in a rat model noninvasively by bracing and to study the corresponding gene-expression profile in the spine and different organs. OVERVIEW OF LITERATURE: Scoliosis involves abnormal lateral curvature of the spine, the causes of which remain unclear. In the literature, it is suggested that scoliosis is genetically heterogeneous, as there are multiple factors involved directly or indirectly in its pathogenesis. Clinical and experimental studies were conducted to understand the etiology of anatomical alterations in the spine and internal organs, as the findings could help clinicians to establish new treatment approaches. METHODS: Twelve female Wistar rats aged 21 days were chosen for this study. Customized braces and real-time polymerase chain reaction (RT-PCR) primers for rats were designed using Primer 3 software. Radiological analysis (X-rays), histopathological studies, SYBR green, and RT-PCR analysis were performed. RESULTS: The spines of six rats were braced in a deformed position, which resulted in a permanent structural deformity as confirmed by X-ray studies. The remaining rats were used as controls. Quantitative studies of the expression of various genes (osteocalcin, pleiotrophins, matrix metalloproteinase-2 [MMP2] and MMP9, TIMP, interleukins 1 and 6, tumor necrosis factor-α) showed their differential expression and significant upregulation (p < 0.05) in different organs of scoliotic rats in comparison to those in control rats. Histopathological findings showed tissue necrosis and fibrosis in the brain, retina, pancreas, kidney, liver, and disc of scoliotic rats. CONCLUSIONS: Bracing is a noninvasive method for inducing scoliosis in an animal model with 100% reliability and with corresponding changes in gene expression. Scoliosis does not just involve a spine deformity, but can be referred to as a systemic disease on the basis of the pathological changes observed in various internal organs.
Animals ; Braces ; Brain ; Congenital Abnormalities ; Female ; Fibrosis ; Gene Expression ; Humans ; Inflammation ; Interleukins ; Kidney ; Liver ; Matrix Metalloproteinase 2 ; Methods ; Models, Animal ; Necrosis ; Pancreas ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Retina ; Scoliosis ; Spine ; Up-Regulation

Tuberculous spondylitis, also known as Pott's disease, is a disease involving the spine with progressive destruction. It most commonly involves the thoracic and lumbosacral spine and may result in severe deformity or neurologic deficit. Although cervical spine involvement is rare, it can cause life threatening event. Recently, 70-year-old man presented with progressive dyspnea and dysphagia. Physical examination and radiologic studies showed a huge retropharyngeal abscess with bony erosion and sclerotic change at the adjacent cervical spine. After incision and drainage, it was finally confirmed as a tuberculous abscess. Herein, we report our experience with literature review.
Abscess ; Aged ; Congenital Abnormalities ; Deglutition Disorders ; Drainage ; Dyspnea ; Humans ; Neurologic Manifestations ; Physical Examination ; Retropharyngeal Abscess ; Spine ; Spondylitis ; Tuberculosis ; Tuberculosis, Spinal

STUDY DESIGN: Retrospective study.PURPOSE: To evaluate the effect of bracing on spinopelvic rotation and psychosocial parameters in adolescents with idiopathic scoliosis (AIS).OVERVIEW OF LITERATURE: Complex three-dimensional deformity in AIS is proposed to influence the spinopelvic parameters and psychosocial condition in adolescents; however, few studies have quantitatively evaluated these parameters.METHODS: Thirty AIS who were prescribed a brace were included in the study. The patients’ standing postero-anterior and total spine radiographs were used to measure the primary curve Cobb angle, vertebral rotation, and pelvic rotation. Apical vertebral rotation (AVR), upper AVR, and lower AVR were measured using the Nash-Moe method. Pelvic rotation was determined using the left-to-right hemipelvic width ratio. The curve pattern was classified as per the Lenke classification system. In all, 14 patients had a type I curve, five had type II, six had type III, one had type IV, and four had type V curves. Brace compliance was subjectively evaluated by interviewing the patients and their parents. The health-related quality of life (HRQOL) and stress level of the recruited patients were assessed using the Brace Questionnaire and Bad Sobernheim Stress Questionnaire, respectively.RESULTS: The Cobb angle significantly decreased with at least 6 months of brace use. AVR correction changed significantly; however, no such results were observed for upper and lower AVR. Pelvic rotation and psychosocial parameters were not significantly affected by brace use. No statistically significant correlation was observed between brace compliance and curve correction.CONCLUSIONS: The Cobb angle and AVR are crucial measurements that help evaluate the treatment efficacy in AIS with small curves who undergo brace treatment. HRQOL and pelvic axial rotation are not influenced by the brace treatment.
Adolescent ; Braces ; Classification ; Compliance ; Congenital Abnormalities ; Humans ; Methods ; Parents ; Pelvis ; Quality of Life ; Retrospective Studies ; Scoliosis ; Spine ; Treatment Outcome

STUDY DESIGN: Retrospective and observational study.PURPOSE: The present study aimed to develop guidelines for segment salvage or sacrifice based on the amount and status of the remnant portion of the vertebra as assessed by coronal magnetic resonance imaging (MRI) in addition to sagittal and axial images in thoracic spine tuberculosis (TB).OVERVIEW OF LITERATURE: Indications for surgery have not changed significantly since the ‘middle path regimen’ was proposed by Tuli. Goals of modern surgical management of spinal TB include debridement of diseased vertebrae, spinal cord decompression, deformity correction, and spine stabilization. However, the extent of decompression has not been defined previously. Too less decompression will lead to compromised neurological recovery, whereas large extent of decompression is associated with increased surgical morbidity and longer segment to reconstruct.METHODS: Sixty-five patients with thoracic spine TB were divided into two groups (segment salvage/sacrifice) based on the thickness of the subchondral bone and endplate morphology of the vertebra as seen on MRI. The operative procedure in the form of instrumentation with Hartshill loop rectangle and sublaminar wire using the simultaneous anterior posterior approach in lateral position (versatile approach) was performed. The patients were analyzed for postoperative fusion, improvement in kyphosis angle, and followed up for development of complications.RESULTS: This method of deciding the level of fixation and segment salvage based on coronal MRI in addition to the sagittal and axial images provided good result in 64 of 65 patients, except for one patient in the segment sacrifice group who had graft buckling and resultant kyphosis.CONCLUSIONS: For segment salvage, having a clear three-dimensional idea about the viable remnant bone is important. Viable salvaged segment reduces the morbidity of the procedure, length of the construct, and unnecessary debridement without compromising on the neural recovery and fusion rate. Hence, additional cone down coronal cuts must be required when MRI is suggestive for spinal TB because it will help in the decision making.
Congenital Abnormalities ; Debridement ; Decision Making ; Decompression ; Humans ; Kyphosis ; Magnetic Resonance Imaging ; Methods ; Observational Study ; Retrospective Studies ; Spinal Cord ; Spine ; Surgical Procedures, Operative ; Transplants ; Tuberculosis

STUDY DESIGN: Review article.OBJECTIVES: To assess the evidence for nonoperative treatment of various degenerative spinal degenerative diseases.SUMMARY OF LITERATURE REVIEW: No study has yet evaluated the evidence for preoperative nonoperative treatment of lumbar spinal diseases.METHODS: The evidence regarding nonoperative treatment for each disease was reviewed through NASS guidelines, and the treatment effect compared to surgical treatment was reviewed through the SPORT series. The efficacy of nonoperative treatment according to disease severity and certain special conditions was investigated through corresponding individual articles.RESULTS: No kind of nonoperative treatment could change the fundamental progression of degenerative spinal disease. The natural course of lumbar disc herniation is favorable regardless of treatment. More than 70% of routine cases improve within 6 weeks. However, it does not take a full 6 weeks to decide whether to perform surgery or not. The evidence for transforaminal epidural steroid injections for short-term pain control is grade A. There is grade B evidence for nonoperative treatment with the goal of mid- to long-term pain control. However, we cannot say that those outcomes are better than the natural course of the disease itself. In cases of radicular weakness, the degree of weakness is correlated with the final outcomes, but it is not evident whether the duration of weakness is correlated with surgical outcomes. Early surgery is usually necessary due to intolerable pain, rather than stable motor weakness. The social cost of herniated discs arises from the loss of patients’ productivity, rather than from direct medical expenses. The natural course of spinal stenosis involves provoked pain and the need for palliative care. Unlike disc herniation, rapid deterioration and marked improvement do not occur. The symptoms of mild to moderate lumbar stenosis are unchanged in 70% of cases, improve in 15%, and worsen in 15%. No study has compared nonoperative treatment with the natural course of the disease. There is no evidence for nonoperative treatment of severe stenosis. Epidural spinal injections are effective for controlling short-term pain. Spontaneous recovery of radicular weakness does not occur, and urgent surgery is necessary in such cases. There is no evidence regarding the natural course and nonoperative treatment of degenerative spondylolisthesis. The working group consensus recommends that it should follow the pattern of nonoperative treatment of spinal stenosis when radicular stenosis symptoms are predominant. Overall, 40%–66% of cases of adult bilateral isthmic spondylolysis progress to symptomatic spondylolisthesis. No studies have investigated nonoperative treatment except physical exercise.CONCLUSIONS: Although short-term symptom amelioration can be achieved by nonoperative treatment, the fundamental progression of the disease is not affected. For conditions excluded from most studies, such as prior spine surgery, cauda equina syndrome, progressive neurological deficit, and uncontrollable severe pain associated with instability, deformity, or vertebral fractures, there were not enough studies to reach informed conclusions. Our review found no evidence regarding nonoperative treatment for such conditions. Furthermore, the treatment methods for each disease are not clearly distinguished from each other, and the techniques used for disc herniation have been applied to other diseases without any evidence.
Adult ; Congenital Abnormalities ; Consensus ; Constriction, Pathologic ; Efficiency ; Exercise ; Humans ; Injections, Spinal ; Intervertebral Disc Displacement ; Palliative Care ; Polyradiculopathy ; Spinal Diseases ; Spinal Stenosis ; Spine ; Spondylolisthesis ; Spondylolysis ; Sports

STUDY DESIGN: Retrospective single institutional observational study. PURPOSE: Segmental spinal dysgenesis (SSD), a complex spinal dysraphic state caused by notochord malformation disorders, is named after its morphological presentation where a spine segment is dysgenetic, malformed or absent. This study’s objective was to examine and reassess SSD imaging findings and correlate them with an embryological explanation. OVERVIEW OF LITERATURE: Scott and his colleagues defined SSD as segmental agenesis or dysgenesis of the lumbar or thoracolumbar vertebrae and underlying spinal cord. Tortori-Donati and his colleagues defined it as a morphologic continuum ranging from hypoplasia to an absent spinal cord segment. METHODS: Fifteen children, whose imaging findings and clinical features were consistent with SSD, were included in the study. Magnetic resonance imaging (MRI) was performed per institutional spine protocol. RESULTS: Five children (33.3%) presented with a high-ending bulbous cord with no caudal segment, six (40%) presented with a dorsal or lumbar segmental dysgenetic cord with a low-lying, bulky caudal cord but without significant spinal canal narrowing, and four (26.6%) presented with segmental caudal dysgenesis with severe kyphoscoliosis, gibbus deformity, and spinal canal narrowing with a normal distal segment (normal or low-lying). CONCLUSIONS: SSD is a complex spinal anomaly in children requiring clinical-radiological assessment followed by multidisciplinary management based on the extent and severity of the dysgenetic cord and the type of SSD. MRI plays a crucial role in both diagnosing and classifying SSD prior to surgical treatment to prevent further impairment.
Child ; Congenital Abnormalities ; Humans ; Magnetic Resonance Imaging ; Notochord ; Observational Study ; Retrospective Studies ; Scoliosis ; Silver Sulfadiazine ; Spinal Canal ; Spinal Cord ; Spine