Spinal Malformations Research Articles

Goldenhar Syndrome: Quality-of-Life Analysis of 43 Consecutive Patients.

Goldenhar syndrome is a rare congenital disease, characterized by the malformation of craniofacial features, spine, and other organs. Its pathogenesis and impact on patients' quality of life (QoL) have not been fully elucidated as yet. Therefore, data of all patients with Goldenhar syndrome, who were treated at Hannover Medical School between 1997 and 2020, were analyzed. Forty-three patients were identified. Their medical records were carefully reviewed for data regarding their age, sex, demographics, Pruzansky classification, surgical history, and affected side. Goldenhar syndrome-associated medical conditions, therapeutic procedures, and the impact of disease on QoL were assessed. Their QoL was assessed using the Oral Health Impact Profile (OHIP)-14 questionnaire. The χ 2 test and Pearson correlation were performed for statistical evaluation. Female sex was positively correlated with OHIP outcomes, whereas male sex had a negative correlation with OHIP outcomes. Therefore, females had significantly worse QoL than males. No significant correlation was observed between the Pruzansky classification and QoL or between surgical history and QoL. Goldenhar syndrome is a rare disease that presents with varying severity. Hence, prospective studies are required to further investigate the impact of Goldenhar syndrome on the QoL.

Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ2 and Fisher exact tests. Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition.

Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine

Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Arthrogryposis is a descriptive term, not a specific disease entity: Escobar Syndrome is an example.

Children born with multiple congenital contractures have been almost always given the diagnosis of arthrogryposis multiplex congenita. Arthrogryposis is a descriptive term, not a specific disease entity. A heterogeneous group of conditions associated with multiple congenital joint contractures (mostly syndromic) should be considered. The records of seven children (four boys and three girls aged 6 months - 11 years) of different ethnic origins have been included in this study. The constellation of specific craniofacial dysmorphic features, spine malformation complex, and appendicular skeletal abnormalities in addition to camptodactyly, talipes equinovarus and rocker-bottom feet were a cluster of malformation complex encountered in our patients. Via comprehensive clinical and imaging study (3D reconstruction CT scan), definite diagnosis of Escobar Syndrome has been approached. The clinical and imaging phenotype was the key factor towards etiological understanding, treatment and genotype confirmation. We identified compound heterozygous mutations (c.459dupA [p.Val154Serfs*24] and c.794T>G [p.Leu265Serfs*24] of the CHRNG gene in four patients. Bilateral flexion contractures of the knees have been treated by using Iliazarov external fixator. Simultaneous corrections of scoliosis have been achieved by applying either dual traditional growing rods or single growing rods. The clinical and radiological phenotypic characterizations are the fundamental tool in differentiating Escobar from other forms of multiple contractures. The aim of this study are three folds, firstly to demonstrate the importance of detecting the etiological understanding in children presented with multiple contractures, secondly to refute the general conception among the vast majority of pediatricians and orthopedic surgeons that arthrogryposis multiplex is a diagnostic entity. And thirdly, we were able to detect severe spine deformity via 3D reconstruction CT scan, namely unsegmented posterior spinal bar.

Analysis of the factors affecting the loss of correction effect in patients with congenital scoliosis after one stage posterior hemivertebrae resection and orthosis fusion

BackgroundTo analyze the factors affecting the loss of correction effect in patients with congenital scoliosis after one stage posterior hemivertebra resection, orthosis, fusion and internal fixation.MethodsThirty-nine patients with congenital scoliosis (CS) who underwent one-stage posterior hemivertebra resection, orthosis, fusion and internal fixation were retrospectively included in Hebei Children’s Hospital General demographic information of patients was collected. Preoperative and postoperative imaging indicators were compared, Including cobb Angle of the main curvature of the spine, segmental Cobb Angle, compensatory cephalic curve, compensatory curve on the caudal side, segmental kyphosis, coronal balance, sagittal balance, thoracic kyphosis, lumbar lordosis, and apical vertebra translation. Correlation analysis is used to evaluate the factors affecting the loss of judgment and correction effect, and the correlation indicators are included in the multi-factor Logistics regression.ResultsIn terms of radiographic indicators in the coronal plane, compared to preoperative values, significant improvements were observed in postoperative Cobb Angle of main curve (8.00°±4.62° vs. 33.30°±9.86°), Segmental Cobb angle (11.87°±6.55° vs. 31.29°±10.03°), Compensatory cephalic curve (6.22°±6.33° vs. 14.75°±12.50°), Compensatory curve on the caudal side (5.58°±3.43° vs. 12.61°±8.72°), coronal balance (10.95 mm ± 8.65 mm vs. 13.52 mm ± 11.03 mm), and apical vertebra translation (5.96 mm ± 5.07 mm vs. 16.55 mm ± 8.39 mm) (all P < 0.05). In the sagittal plane, significant improvements were observed in Segmental kyposis Angle (7.60°±9.36° vs. 21.89°±14.62°, P < 0.05) as compared to preoperative values. At the last follow-up, Segmental kyphosis Angle (6.09°±9.75° vs. 21.89°±14.62°, P < 0.05), Thoracic kyphosis (26.57°±7.68° vs. 24.06°±10.49°, P < 0.05) and Lumbar lordosis (32.12°±13.15° vs. 27.84°±16.68°, P < 0.05) had statistical significance compared with the preoperative department. The correlation analysis showed that the correction effect of the main curve Cobb angle was correlated with fixed segment length (rs=-0.318, P = 0.048), postoperative segment Cobb angle (rs=-0.600, P < 0.001), preoperative apical vertebra translation (rs = 0.440, P = 0.005), and spinal cord malformation (rs=-0.437, P = 0.005). The correction effect of segmental kyphosis was correlated with age (rs = 0.388, P = 0.037). The results of the multivariate logistic regression analysis revealed that postoperative segmental Cobb angle > 10° (OR = 0.011, 95%CI:0.001–0.234, P = 0.004), associated spinal cord anomalies (OR = 24.369, 95%CI:1.057-561.793, P = 0.046), and preoperative apical translation > 10 mm (OR = 0.012, 95%CI:0.000-0.438, P = 0.016) were influential factors in the progression of the main curve Cobb angle.ConclusionThe one-stage posterior hemivertebra resection and short-segment corrective fusion with internal fixation are effective means to treat congenital scoliosis. However, attention should be paid to the loss of correction and curve progression during follow-up. Patients with spinal cord malformation and a large preoperative apical vertebra translation have a greater risk of losing the correction after surgery.

Anorectal Malformations: Epidemiological, Clinical, Therapeutic and Evolutionary Aspects in the General Surgery Department of the Sominé DOLO Hospital of Mopti

We conducted a retrospective and prospective study. In our study, we collected 35 cases of MAR, including 21 boys and 14 girls, over a period of 4 years, from January 2017 to December 2020. We recorded an average of 8.7 cases of ADR per year. They are more frequent in boys, with a sex ratio of 1.5. The majority of our patients came from the Mopti region and were of Dogon ethnicity. Most of the malformations were discovered by the parents, given that 54.3% of the mothers had given birth in a health centre and the malformed children were most often seen in a state of intestinal obstruction or sub-occlusion requiring an emergency colostomy. The diagnosis was made during the systematic examination of the newborn in the delivery room in 8.57% of our patients. Low forms were more frequent (48.6%). Invertograms were performed in 15 patients (42.9%). Abnormalities associated with MAR were dominated by spinal malformations in 4 cases (11.4%). In terms of treatment, the operative techniques used, in order of frequency, were: ASARP 8 cases (30.8%); Pena PSARP 15 cases (57.7%), YV Proctoplasty 2 cases (7.7%) and PENA PSARP plus MOLLARD AP 1 case (3.8%). Average follow-up was 12 months. Four (4) patients (15.4%) were lost to follow-up. Post-operative follow-up was favourable in 17 patients (65.4%); 4 cases of death and 1 case of anal stenosis.

A Novel Splice Site Mutation in the FBN2 Gene in a Chinese Family with Congenital Contractural Arachnodactyly

Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by arachnodactyly, multiple joint contractures, progressive kyphoscoliosis, pectus deformity and abnormal crumpled ears. FBN2 is the only gene currently known to be associated with CCA. In this study, we report on a prenatal case presented with skeletal, cardiac and spinal malformations. And his father had elongated limbs, contractures of the proximal interphalangeal joints, high myopia and scoliosis. We conducted whole exome sequencing (WES) on the fetus-parental trio and a heterozygous variant (hg19 chr5:127,673,685, c.3598 + 4A > G, NM_001999.4) in intron 27 of the FBN2 gene was successfully identified, inherited from the father. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (126 bp) by disrupting the splice-donor site and destroyed the 17th calcium-binding epidermal growth factor-like (cbEGF) domain. Our research not only finds the etiology of the disease in affected individuals and expands the mutation spectrum of FBN2 gene, but also provides genetic counseling and fertility guidance for this family.

Cobb Syndrome Associated with Spinal Cavernoma – Case Report

AbstractCobb syndrome, or cutaneomeningospinal angiomatosis, is a rare condition that affects young adults, and its etiology has not been completely elucidated. It is characterized by a cutaneous sign, or stigma, associated with spinal or intracranial malformations. The symptoms are quite diverse, but, in most cases, the disease presents motor deficit and pain. The present study reports the case of a 48-year-old female patient, who initially sought dermatological medical care for a single skin lesion in the posterior cervical region. During the excision, it was noticed that the lesion had contiguous behavior to the deep anatomical planes, thus requiring the evaluation of the neurosurgical team. The purpose of this report is to describe this rare disease, covering more details about diagnosis and therapy.

Surgical Outcomes of Symptomatic Intramedullary Spinal Cord Cavernous Malformations: Analysis of Consecutive Cases in a Single Center.

Intramedullary spinal cavernous malformations (ISCMs) are rare vascular lesions of the spinal cord with unclear natural history and controversy over treatment. This study aimed to report a series of symptomatic ISCMs underwent microsurgical management to illustrate the natural history, clinical presentation, and surgical outcomes and to evaluate factors associated with hemorrhage events and neurological prognosis. This single-center retrospective study included 29 consecutive patients with whose demographic, symptomology, imaging, neurological, and surgical data were collected. The risk for hemorrhage events and factors affecting surgical outcomes were retrospectively analyzed. There were 12 female (41.4%) and 17 male patients (58.6%), with an average age of 45.2 years (range, 17-69 years). The mean size of the lesion was 9.7 mm (range, 3-20 mm). Most patients had a bowel or/and bladder dysfunction symptom (n = 11, 37.9%), followed by sensory deficits (n = 5, 17.2%), gait disturbance (n = 5, 17.2%), pain (n = 4, 13.8%), and weakness (n = 4, 13.8%), most (n = 15, 51.7%) with a chronic onset. All patients received total resection without rehemorrhages after surgical resection in follow-up. Sixty-five point five percent patients (n = 19) improved, 13.8% (n = 4) remained stable, 20.7% (n = 6) got worsen. The overall annual hemorrhage risk was 2.1% per patient-year. A total of 27 hemorrhages occurred in the 18 patients, of which rehemorrhage rate increased to 50.0% (n = 9) with a previous history of hemorrhage. Patients with smaller lesion sizes were more likely to have hemorrhage or rehemorrhage events (p = 0.008). Recurrent hemorrhage of the lesions was a risk factor for neurological outcomes (p = 0.016). The risk of rehemorrhage was significantly increased in symptomatic ISCM patients with a previous history of hemorrhage. Rehemorrhage was a risk factor for neurological outcomes. Patients can benefit from microsurgical treatment to avoid rehemorrhage and further neurological deterioration.

Commentary on "Surgical Outcomes of Symptomatic Intramedullary Spinal Cord Cavernous Malformations: Analysis of Consecutive Cases in a Single Center".

Commentary on "Surgical Outcomes of Symptomatic Intramedullary Spinal Cord Cavernous Malformations: Analysis of Consecutive Cases in a Single Center".

Surgical Detethering of a Type I Split Spinal Cord Malformation in an Adult: 2-Dimensional Operative Video.

Surgical Detethering of a Type I Split Spinal Cord Malformation in an Adult: 2-Dimensional Operative Video.

Audiological phenotyping evaluation in KBG syndrome: Description of a multicenter review.

Our objective was to reinforce clinical knowledge of hearing impairment in KBG syndrome. KBG syndrome is a rare genetic disorder due to monoallelic pathogenic variations of ANKRD11.The typical phenotype includes facial dysmorphism, costal and spinal malformation and developmental delay. Hearing loss in KBG patients has been reported for many years, but no study has evaluated audiological phenotyping from a clinical and an anatomical point of view. This French multicenter study included 32 KBG patients with retrospective collection of data on audiological features, ear imaging and genetic investigations. We identified a typical audiological profil in KBG syndrome: conductive (71%), bilateral (81%), mild to moderate (84%) and stable (69%) hearing loss, with some audiological heterogeneity. Among patients with an abnormality on CT imaging (55%), ossicular chain impairment (67%), fixation of the stapes footplate (33%) and inner-ear malformations (33%) were the most common abnormalities. We recommend a complete audiological and radiological evaluation and an ENT-follow up in all patients presenting with KBG Syndrome. Imaging evaluation is necessary to determine the nature of lesions in the middle and inner ear.

Prevalence of congenital malformations of the lumbar spine in pre-occupational exams

Background: the vertebral column is a structure that develops over a short period of time, which makes it vulnerable to alterations in its morphology and vertebral conformation. Its embryological development occurs in early stages, between the fourth and sixth week approximately. These alterations can give rise to the appearance of congenital anomalies, which, if functionally viable in the neonatal/infantile period, can generate pain syndromes in working age, which increases the number of work absenteeism. Plain radiography is the most widely used diagnostic modality at the time of diagnosis of these congenital entities, as well as their clinical follow-up. The objective of this work is to know the prevalence of congenital malformations of the lumbar spine in a company that receives occupational medicine during 2021. Material and methods: front and profile lumbar spine radiographs were used, with a radiological report by a specialist, to patients who attended the company from January 2021 to December 2021. From this, the total number of patients evaluated was taken and prevalence statistics were performed congenital pathology of the lumbar spine. Results: Of the 855 patients studied, the presence of congenital lumbar malformation was found in 138, that is, 16,14 % of the total. Conclusion: Lumbar congenital malformation is a problem for the population of active working age. Given the high prevalence, it reinforces the need to carry out complete pre-occupational studies for primary health prevention in workers who may develop low back pain.

Teratogenic effects of the dicamba herbicide in Zebrafish (Danio rerio) embryos

Dicamba has been used worldwide for 60 years, but few studies have been conducted on its environmental safety and health effects. Therefore, this study aims to evaluate the acute toxicity, teratogenic effects, oxidative stress, and neurotoxicity of Dicamba in zebrafish embryos. Embryos were exposed to concentrations of 4.5, 18, 72, and 288 mg/L of Dicamba for 96 h. Among the teratogenic effects, yolk sac edema predominated, besides malabsorption of nutrients (grayish yolk sac). The presence of edema may indicate problems with circulation and water efflux from the embryos, which may be related to kidney and cardiovascular problems. Other effects such as hemorrhage, spinal and eye malformations, and dwarfism were also observed. The hatching rate was reduced in the highest concentration, and in the other concentrations, a decrease was noticeable indicating a delay in development. Neurotoxic effects were also observed. Oxidative stress analysis showed a significant decrease in SOD at all concentrations and an increase in GPx, GSH, and LPO at 288 mg/L of Dicamba. It was observed that the herbicide is capable of causing teratogenic effects, developmental delay, and oxidative stress. These results show that exposure to Dicamba, in a commercial formulation, can bring risks during embryonic development. In addition, it highlights the need for further studies on the effects of the herbicide and a reassessment of toxicity categorization.

Acceptance of Early Surgery for Treatment of Spinal Cord Cavernous Malformation in Contemporary Japan.

Spinal cord cavernous malformation (CM) is an intramedullary vascular lesion that may present with progressive symptoms. Surgery is recommended for symptomatic patients, but optimal timing of surgery is debatable. Some advocate waiting until plateau of neurological recovery and others support emergency surgery. There is no statistic on how commonly these strategies are utilized. We aimed to find contemporary practice pattern among neurosurgical spine centers in Japan. A database of intramedullary spinal cord tumors assembled by Neurospinal Society of Japan was surveyed and 160 patients with spinal cord CM were identified. Neurological function, disease duration, and number of days between presentation to hospitals and surgery were analyzed. Duration of disease before presentation to hospitals ranged from 0 to 336 months (median, 4 months). Number of days between patients' presentation and surgery ranged from 0 to 6,011 days (median, 32 days). Time from symptom onset to surgery ranged from 0 to 336.9 months (median, 6.6 months). Patients with severe preoperative neurological dysfunction had shorter duration of disease, fewer days between presentation and surgery, and shorter time between symptom onset and surgery. Patients with paraplegia or quadriplegia were more likely to improve when operated on within 3 months from onset. Timing of surgery for spinal cord CM in Japanese neurosurgical spine centers generally was early, with 50% of patients undergoing surgery within 32 days after presentation. Further study is needed to clarify optimal timing of surgery.

The Reality of Benefit in Surgical Removal for Spinal Cord Cavernous Malformation: Commentary on "Acceptance of Early Surgery for Treatment of Spinal Cord Cavernous Malformation in Contemporary Japan".

The Reality of Benefit in Surgical Removal for Spinal Cord Cavernous Malformation: Commentary on "Acceptance of Early Surgery for Treatment of Spinal Cord Cavernous Malformation in Contemporary Japan".

Evaluation of Anal Sphincter with High Resolution Anorectal Manometry and 3D Reconstruction in Patients with Anorectal Malformation

Background: Patients with anorectal malformation (ARM) need long-term follow-up, in order to evaluate fecal continence; the main predictors of longer-term success are the type of ARM, associated anomalies and sacral integrity. Three-Dimensional High Resolution Anorectal Manometry (3D-HRAM) gives detailed information on pressure on the anal complex profile. Our objective was to analyze anal sphincter activity in ARM patients with 3D-HRAM establishing the correlation between manometric and clinical data. Methods: Forty ARM patients were submitted to 3D-HRAM: manometric, anatomical and clinical scores were correlated with each other and with the bowel management response (BM). Results: A positive correlation between all scores and types of ARM was found: in high ARM and in patients with spinal anomalies (regardless to ARM type) lower scores were reported and even after BM they did not achieve good continence. Conclusions: 3D-HRAM gives detailed data on the functional activity of the anal sphincter complex. Our study revealed a correlation between manometric parameters and clinical outcomes, confirming spinal malformations and ARM type as the most important prognostic risk factors for a bad outcome. Specific sphincteric defects can also be explored with manometry, allowing for tailored bowel management strategies.

Radiation-induced cavernous malformations in the spine: patient series.

Radiation-induced spinal cord cavernous malformations (RISCCMs) are a rare subset of central nervous system lesions and are more clinically aggressive than congenital cavernous malformations (CMs). The authors assessed the characteristics and outcomes of patients with RISCCM at a single institution and systematically reviewed the pertinent literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among the 146 spinal CMs at the authors' institution, 3 RISCCMs were found. Symptom duration ranged from 0.1 to 8.5 months (mean [standard deviation], 3.2 [4.6] months), and latency ranged from 16 to 29 years (22.4 [9.6] years). All 3 RISCCMs were surgically treated with complete resection; 2 patients had stable outcomes, and 1 improved postoperatively. A review of 1240 articles revealed 20 patients with RISCCMs. Six of these patients were treated with resection, 13 were treated conservatively, and in 1 case, the treatment type was not stated. Five of the 6 patients treated surgically reported improvement postoperatively or at follow-up; 1 was stable, and none reported worsened outcomes. RISCCMs are rare sequelae following radiation that inadvertently affect the spinal cord. Altogether, the frequency of stable and improved outcomes on follow-up suggests that resection could prevent further patient decline caused by symptoms of RISCCM. Therefore, surgical management should be considered primary therapy in patients presenting with RISCCMs.

Evaluation of split cord malformation between years 2006 and 2020: A case series study

BackgroundSplit spinal cord malformation (SCM) is a rare congenital disorder leading to the split of the spinal cord by a bony or fibrous septum. ObjectivesIn the current study, we aimed to evaluate the patients with SCM who underwent surgery between 2006 and 2020. MethodsIn this case series, thirty-five patients with SCM who underwent septal resection or spinal cord release surgery were enrolled and evaluated for type and site of the septum, accompanying some anomalies, such as neurological abnormalities, spinal deformities, and skin lesions. Also, the changes of neurological symptoms after surgery were securitized. ResultsThirty-five patients, including 27 females and 8 males, have been investigated. Scoliosis and Tethered cord syndrome were the most prevalent anomalies in 24 and 26 patients, respectively. The most common skin lesion was focal hirsutism in 14 patients, and the most common neurological disorder was the reduced muscle force observed in 5 patients, which was improved in two cases following surgeries. ConclusionSCM occurred more frequently in females in comparison with males (77.14% in females and 22.85% in males). Scoliosis and Tethered cord syndrome were two dominant accompanying disorders with SCM. Moreover, focal hirsutism and reduced muscle force were the most common skin lesion and neurological disorders, respectively in these patients, respectively.

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.

Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway.