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We present a case of Klippel-Feil Syndrome, a congenital skeletal defect where multiple cervical vertebral bodies are fused. Klippel-Feil Syndrome has multiple associated anomalies, with a notable one being Sprengel's deformity. In this case, the patient was given a diagnosis of Klippel-Feil Syndrome prenatally after suspected cervical vertebrae fusion and Sprengel's deformity were seen on both fetal magnetic resonance imaging (MRI) and ultrasound. Prenatal diagnosis of Sprengel's deformity has been reported once in the literature. In this report, we present imaging findings of Sprengel's deformity seen in association with Klippel-Feil Syndrome using a combination of fetal ultrasound and MRI.

OBJECTIVE: To introduce a new occipitocervical angle parameter, occipito-odontoid angle (O-Da), for predicting dysphagia after occipitocervical fusion (OCF) in patients with C(2, 3) Klippel-Feil syndrome (KFS) and analyze its effectiveness. METHODS: A total of 119 patients met selective criteria between April 2010 and November 2019 were retrospectively included as the study subjects. There were 56 males and 63 females. The age ranged from 14 to 76 years, with a median age of 51 years. There were 44 cases of basilar invagination and 75 cases of atlantoaxial subluxation. Forty patients were combined with C(2, 3) KFS. Seven patients underwent anterior decompression combined with posterior OCF and 112 patients underwent posterior OCF. The fixed segments were O-C(2) in 36 cases, O-C(3) in 51 cases, O-C(4) in 25 cases, and O-C(5) in 7 cases. All patients were followed up 21-136 months, with a median time of 79 months. The lateral cervical X-ray films before operation and at last follow-up were used to measure the occipital to C(2) angle (O-C(2)a), the occipital and external acoustic meatus to axis angle (O-EAa), the occipital protuberance to axial angle (Oc-Axa), the O-Da, and the narrowest oropharyngeal airway space (nPAS). The differences of the above parameters between the last follow-up and the preoperative values were calculated (represented as dO-C(2)a, dO-EAa, dOc-Axa, dO-Da, and dnPAS). Patients were divided into two groups according to whether they suffered dysphagia after operation, and the differences in clinical data and radiographic parameters were compared between the two groups. The correlation between occipitocervical angle parameters and nPAS in 40 patients with C(2, 3) KFS was analyzed respectively. In addition, sensitivity and specificity analyses were used to assess the effectiveness of dO-Da≤−5° for the prediction of postoperative dysphagia. RESULTS: Thirty-one patients (26.1%) suffered dysphagia after OCF (dysphagia group), including 10 patients with C(2, 3) KFS; no dysphagia occurred in 88 patients (non-dysphagia group). There was no significant difference in age, follow-up time, fixed segment, proportion of patients with rheumatoid arthritis, proportion of patients with atlantoaxial subluxation, and proportion of patients with C(2, 3) KFS between the two groups (P>0.05). The proportion of female patients was significantly higher in dysphagia group than in non-dysphagia group (χ(2)=7.600, P=0.006). The difference in preoperative O-C(2)a between the two groups was significant (t=2.528, P=0.014). No significant differences were observed in preoperative O-EAa, Oc-Axa, O-Da, and nPAS (P>0.05). There was no significant difference in dO-C(2)a, dO-EAa, dOc-Axa, dO-Da, and dnPAS between the two groups (P>0.05). The dO-C(2)a, dO-EAa, dOc-Axa, and dO-Da were positively correlated with dnPAS in 40 patients with C(2, 3) KFS (r=0.604, P

RIPPLY2 is an essential part of the formation of somite patterning during embryogenesis and in establishment of rostro-caudal polarity. Here, we describe three individuals from two families with compound-heterozygous variants in RIPPLY2 (NM_001009994.2): c.238A > T, p.(Arg80*) and c.240-4 T > G, p.(?), in two 15 and 20 year old sisters, and a homozygous nonsense variant, c.238A > T, p.(Arg80*), in an 8 year old boy. All patients had multiple vertebral body malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae. The nonsense variant can be classified as likely pathogenic based on the ACMG criteria while the splice variants must be classified as a variant of unknown significance. With this report on two further families, we confirm RIPPLY2 as the gene for SCDO6 and broaden the phenotype by adding myelopathy with or without spinal canal stenosis and spinal spasticity to the symptom spectrum. This article is protected by copyright. All rights reserved.

INTRODUCTION: Klippel–Feil Syndrome is the congenital fusion of at least two cervical vertebrae. Often asymptomatic, though in rare cases it may lead to severe cervical spine deformity and neurologic injury. CASE PRESENTATION: We report a case of a 48-year-old woman with a history of Klippel–Feil Syndrome and congenital scoliosis who developed progressive cervical myelopathy. She was surgically treated with anterior C5 corpectomy and arthrodesis. Pre-operative evaluation was facilitated by 3D printed models. The surgical decompression and spinal reconstruction was completed with the use of a patient-specific, custom-made cervical spine locking plate. DISCUSSION: Pre-operative evaluation with 3D printing technology was useful in understanding the patient’s complex curve pattern and in designing a patient specific implant. Custom designed implant is a reasonable option to treat cervical myelopathy associated with complex cervical deformity.

Split cord malformation (SCM) is a developmental disorder that is usually symptomatic and diagnosed in childhood. The majority of these lesions are in the thoracic and lumbar spine, with only 1%-3% of cases found in the cervical spine. This is a case report of a 55-year-old female patient with an unremarkable medical history who presented with neck pain. Upon workup, she was found to have extensive developmental anomalies throughout her cervical and thoracic spine, including an incidentally found type 2 SCM and multiple autofused vertebrae. There are only 6 similar studies published in the literature. There was extensive facet degeneration in her cervical spine, which was suspected to be the etiology of her neck pain. This case illustrates the rare finding of asymptomatic adult cervical SCM and the likely significance of her autofused vertebrae causing accelerated symptomatic facet spondylosis.

BackgroundKlippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity.MethodsWe consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis.ResultsWe primarily examined rare variants in five reported genes (GDF6,MEOX1, GDF3, MYO18BandRIPPLY2) associated with KFS and detected three variants of uncertain significance inMYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identifiedBAZ1Bas having the highest probability of association with KFS, followed byFREM2,SUFU,VANGL1andKMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls.ConclusionsOur study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.

Background Although adjacent segment disease (ASD) following anterior cervical fusion has been well described in the literature, there is relative paucity of data on this pathology after posterior cervical fusion. To our knowledge, there have been no reported cases of proximal ASD following posterior fusion to C2. Case Description We present 2 cases of proximal ASD presenting as retroodontoid pseudotumors following posterior fusion to C2, both in middle-aged females without history of rheumatologic disease. The first occurred in a patient with Klippel-Feil deformity 13 years after C2-6 posterior cervical fusion, the second in a patient 3 and a half years following revisional circumferential C2-T2 fusion. Both were successfully treated with proximal extension of laminectomy and fusion to the occiput, supplemented in the first patient by transdural decompression of retroodontoid mass. Conclusions Proximal ASD can manifest as retroodontoid pseudotumor at variable time intervals following posterior fusion to C2. Clinicians must account for this possibility in their decision making.

An adult with Sprengel deformity and Klippel-Feil syndrome associated with an omovertebral bone has rarely been reported in literature. The omovertebral bone is an abnormal cartilaginous connection between the scapula and the cervical spine. Limited cases have previously been reported in the literature describing surgical intervention when neurologic deficits such as cervical myelopathy or radiculopathy are present. In the present case, an omovertebral bone extended into the cervical lamina resulting in cervical myeloradiculopathy requiring resection of the bony anomaly and cervicothoracic fusion. The omovertebral bone as an etiology for radiculopathy or myelopathy is rarely seen in an adult population, and surgical decompression and fusion should be considered with this constellation of anomalies.

Klippel-Feil syndrome (KFS) occurs due to failure of vertebral segmentation during development. Minimal research has been done to understand the prevalence of associated symptoms. Here, we report one of the largest collections of KFS patient data. Data were obtained from the CoRDS registry. Participants with cervical fusions were categorized into Type I, II, or III based on the Samartzis criteria. Symptoms and comorbidities were assessed against type and location of fusion. Seventy-five patients (60F/14M/1 unknown) were identified and classified as: Type I, n = 21(28%); Type II, n = 15(20%); Type III, n = 39(52%). Cervical fusion by level were: OC–C1, n = 17(22.7%), C1–C2, n = 24(32%); C2–C3, n = 42(56%); C3–C4, n = 30(40%); C4–C5, n = 42(56%); C5–C6, n = 32(42.7%); C6–C7, n = 25(33.3%); C7–T1, n = 13(17.3%). 94.6% of patients reported current symptoms and the average age when symptoms began and worsened were 17.5 (± 13.4) and 27.6 (± 15.3), respectively. Patients reported to have a high number of comorbidities including spinal, neurological and others, a high frequency of general symptoms (e.g., fatigue, dizziness) and chronic symptoms (limited range of neck motion [LROM], neck/spine muscles soreness). Sprengel deformity was reported in 26.7%. Most patients reported having received medication and invasive/non-invasive procedures. Multilevel fusions (Samartzis II/III) were significantly associated with dizziness (p = 0.040), the presence of LROM (p = 0.022), and Sprengel deformity (p = 0.036). KFS is associated with a number of musculoskeletal and neurological symptoms. Fusions are more prevalent toward the center of the cervical region, and less common at the occipital/thoracic junction. Associated comorbidities including Sprengel deformity may be more common in KFS patients with multilevel cervical fusions. These slides can be retrieved under Electronic Supplementary Material.

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.

Klippel-Feil syndrome 4 (KFS4; MIM# 616549) is an autosomal recessive disorder caused by biallelic pathogenic variants in MYO18B and comprises, in addition to Klippel-Feil anomaly (KFA), nemaline myopathy, facial dysmorphism, and short stature. We aim to outline the natural history of KFS4 and provide an updated description of its clinical, radiological, laboratory, and molecular findings. We comprehensively analyzed the medical records of 6 Saudi and 1 American patients (including 5 previously unpublished cases) with a molecularly confirmed diagnosis of KFS4. All patients had myopathy of varying severity that followed a slowly progressive or non-progressive course, affecting primarily the proximal musculature of the lower limb although hand involvement with distal arthrogryposis and abnormal interphalangeal creases was also observed. KFA and characteristic dysmorphic features, including ptosis and bulbous nose, were observed in all but two patients. The causal MYO18B variants were a founder NM_032608.5:c.6905C>A; p.(Ser2302*) variant in the Saudi patients (P1-P6) and a novel MYO18B homozygous variant (c.6660_6670del;p.[Arg2220Serfs*74]) in the American Caucasian patient (P7). We report the phenotypic and genetic findings in seven patients with KFS4. We describe the natural history of this disease, confirm myopathy as a universal feature and describe its pattern and progression, and note interesting differences between the phenotypes observed in patients with KFA and those without.

STUDY DESIGN A retrospective, case series. OBJECTIVE The aim of this study is to evaluate the concomitant anomalies in patients with Sprengel deformity (SD). SUMMARY OF BACKGROUND DATA SD is the most common congenital anomaly of the shoulder. One or more associated anomalies may coexist in SD patients, similar to congenital scoliosis (CS); however, these anomalies and their relationship have not been studied in detail previously. METHODS SD patients who have applied to our institution between 2005 and 2019 were retrospectively reviewed. The patients were evaluated clinically and radiologically. The patients were divided in two groups as SD patients with CS and without CS, to analyze if these anomalies are present due to CS or SD. Physical examination findings, MRI, CT, and USG reports were analysed for accompanying pathologies. Patients with missing data were excluded. Student-t and Fisher's exact tests were used to compare the groups. Significance value was set as p = 0.05. RESULTS Ninety patients met inclusion criteria. The most common spinal anomaly was omovertebra, followed by spina bifida and Klippel-Feil. Tethered cord and diastematomiyelia were associated with CS (P = 0.0026 and P = 0.0057, respectively). The most common extra-skeletal anomaly was rib anomalies, followed by urinary and cardiac system anomalies. Rib anomalies were associated with CS (P = 0.00001). CONCLUSION Concomitant anomalies may accompany SD. The prognosis of SD may be affected by these anomalies. Therefore, patients should be evaluated for possible coexistent congenital anomalies. LEVEL OF EVIDENCE 4.

Sprengel shoulder, Klippel-Feil syndrome and congenital scoliosis are associated conditions. Cervical myelopathy in a child due to a concomitant omovertebral bar causing posterior cord compression and a hypermobile cervical disc protrusion adjacent to fused cervical segments causing anterior compression at the same level is very rare. We report the presentation, findings, surgical management and results of treatment in such a child.A 9-year-old girl with Sprengel shoulder presented with cervical myelopathy (Frankel D). Imaging revealed a bony omovertebral bar connected to the left scapula compressing the spinal cord posteriorly through a lamina defect at C5 resulting in significant cervical stenosis. A hypermobile disc protrusion adjacent to congenitally fused segments resulted in anterior compression at the same level. She was treated surgically with cervical laminectomy and instrumented fusion, excision of the omovertebral bar and modified Woodward procedure for the left Sprengel shoulder.At 2 year follow-up, she had improved neurologically (Frankel E) and there was improved shoulder symmetry and abduction. MRI showed resolution of cervical stenosis. Although there was no significant progression of congenital scoliosis, it will need to be monitored.Cervical myelopathy due to an omovertebral bar and cervical disc protrusion in a child with Klippel-Feil syndrome and Sprengel shoulder is a rare presentation and can be treated with a single posterior approach addressing both pathologies.

Study design Retrospective study. Objective To define distinct Klippel-Feil syndrome (KFS) patient phenotypes that are associated with the need for surgical intervention. Summary of background data KFS is characterized by the congenital fusion of cervical vertebrae; however, patients often present with a variety of other spinal and extraspinal anomalies suggesting this syndrome encompasses a heterogeneous patient population. Moreover, it remains unclear how the abnormalities seen in KFS correlate to neurological outcomes and the need for surgical intervention. Methods Principal component (PC) analysis was performed on 132 KFS patients treated at a large pediatric hospital between 1981 and 2018. Thirty-five variables pertaining to patient/disease-related factors were examined. Significant PCs were included as independent variables in multivariable logistic regression models designed to test associations with three primary outcomes: cervical spine surgery, thoracolumbar/sacral spine surgery, and cranial surgery. Results Fourteen significant PCs accounting for 70% of the variance were identified. Five components, representing four distinct phenotypes, were significantly associated with surgical intervention. The first group consisted of predominantly subaxial cervical spine fusions, thoracic spine abnormalities and was associated with thoracolumbar/sacral spine surgery. The second group was largely represented by axial cervical spine anomalies and had high association with cervical subluxation and cervical spine surgery. A third group, heavily represented by Chiari malformation, was associated with cranial surgery. Lastly, a fourth group was defined by thoracic vertebral anomalies and associations with sacral agenesis and scoliosis. This phenotype was associated with thoracolumbar/sacral spine surgery. Conclusion This is the first data-driven analysis designed to relate KFS patient phenotypes to surgical intervention and provides important insight that may inform targeted follow-up regimens and surgical decision-making. Level of evidence 3.

Objective To analyze clinical and radiologic features of pathologic atlantoaxial displacement (PAAD) in pediatric patients and to compose a treatment algorithm for anomaly-related PAAD. Background Criteria of different types of PAAD and treatment algorithms have been widely reported in the literature but are difficult to apply to patients with odontoid abnormalities, C2-C3 block, spina bifida C1, and children. Methods We evaluated results of treatment of 29 pediatric patients with PAAD caused by congenital anomalies of the craniovertebral junction (CVJ), treated in Ilizarov Center in 2009–2017, including 20 patients with atlantoaxial displacement (AAD) and 9 patients with atlantoaxial rotatory fixation. Results There were 14 males (48.3%) and 15 females (51.7%). We singled out 3 groups of patients: nonsyndromic (6 patients, 20.7%), Klippel-Feil syndrome (13 patients, 44.8%), and syndromic (10 patients, 34.5%). Odontoid abnormalities and C1 dysplasia were widely represented in the syndromic group. Local symptoms predominated in the nonsyndromic and KFS groups. In the syndromic group, all patients had AAD and myelopathy. A pronounced decrease of space available for chord C1 and increase of anterior atlantodental interval were noted compared with other groups. Conclusions We present a unified treatment algorithm of pediatric anomaly-related PAAD. Syndromic AAD are often accompanied by anterior and central dislocation and myelopathy and atlantooccipital dissociation. These patients require early aggressive surgical treatment. Nonsyndromic and Klippel-Feil syndrome AAD, atlantoaxial subluxation, and atlantoaxial fixation often manifest by local symptoms and need to eliminate CVJ instability. Existing classifications of symptomatic atlantoaxial displacement are not always suitable for patients with CVJ abnormalities.

Common carotid artery usually bifurcates at the superior border of thyroid cartilage, corresponding to the C3-4 junction, however bifurcation level may vary. Common carotid bifurcation may have rare variations like separate origins of left internal and external carotid arteries from aortic arch, or bifurcation of common carotid artery within thoracic cavity. Intrathoracic carotid bifurcation is a rare variation with limited number of cases reported. The occurrence of a low carotid bifurcation seems to be embryologically related to the persistence of the ductus caroticus. Additionally, intrathoracic carotid bifurcation can be accompanied by findings of Klippel-Feil syndrome. Herein, we present imaging findings of an incidentally detected intrathoracic left common carotid artery bifurcation in a pediatric patient accompanied by fusion of the cervical vertebrae and ribs.

Coexistence of Klippel-Feil syndrome with Sprengel deformity and omovertebral bone is a rare complex bone abnormality with unknown incidence and etiology. Herein, we report a case of a 6-year-old girl with coexistence of these congenital abnormalities evaluated by three-dimensional computed tomography. We also make a brief review and discuss in details the role of this imaging modality in the evaluation of such complex cases.

Background A rare case of familial genetic disorder Klippel-Feil syndrome and Arnold-Chiari malformation caused by cervical spondylotic myelopathy was reported here. Case Description The reconstruction of stability and spinal cord decompression was achieved by anterior cervical discectomy, fusion, and internal fixation. Conclusions Although the disease genetic characteristics have been studied, operation is necessary when it leads to abnormal neurologic symptoms and the surgery of surgery can have a beneficial outcome.

We present the case of an accidental extubation in a prone-positioned patient with a challenging airway because of Klippel-Feil syndrome and previous cervical spine fusions. The surgical procedure was well underway when this occurred, which added substantially to the difficulties produced by this event. We herein highlight the corrective steps we took in our case. We also recommend the need for a comprehensive preoperative briefing with all operating room personnel together with an action plan for how to prevent this particular scenario.

Patients with Klippel-Feil syndrome (KFS) have an increased incidence of vascular anomalies as well as vertebral artery (VA) anomalies. In this article, we presented imaging findings of a 15-year-old female patient with KFS with a rare association of extraforaminal cranially ascending right VA that originated from the ipsilateral carotid bulb. Trifurcation of the carotid bulb with VA is a very unusual variation and to the best of our knowledge, right-sided one has not been reported in the literature.

Background Klippel-Feil syndrome (KFS) is characterized by congenital vertebral fusion of the cervical spine and a wide spectrum of associated anomalies. In patients with KFS with basilar invagination (BI), compression of the brainstem and upper cervical cord results in neurological deficits, and decompression and occipitocervical reconstruction are required. The highly varied anatomy of KFS makes a posterior occipitocervical fixation strategy challenging. For these patients, the transoral atlantoaxial reduction plate (TARP) operation is an optimal option to perform a direct anterior fixation to achieve stabilization. Objective To evaluate the effectiveness of TARP internal fixation for the treatment of BI with KFS. Methods Ten consecutive patients with BI and KFS who underwent TARP reduction and fixation from 2010 to 2012 were reviewed. Clinical assessment and image measurements were performed preoperatively and at the most recent follow-up. Nine patients (9/10) were followed for an average of 31.44 months. Results Symptoms were alleviated in 9 of 9 patients (100.00%). The odontoid process was ideally corrected with the TARP system. The mean clivus canal angle improved from 124° preoperatively to 152° postoperatively. The average preoperative and postoperative Japanese Orthopedic Association scores were 10.56 (n = 9) and 14.67 (n = 9), respectively, indicating 63.82% improvement. There was bony bridge catenation on the computed tomography scans and no evidence of hardware failure at 6 months. Conclusion The TARP operation is effective and safe for treating patients with BI with KFS. The midterm clinical results were satisfactory.

Study Objective The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is characterized by vaginal and uterine aplasia in a 46,XX individual. Multiple abnormalities may be associated with MRKH syndrome, and it appears to overlap other syndromes. The aim of this study was to describe the spectrum of associated malformations and syndromes as well as abnormal karyotypic findings in a large cohort of 346 patients. Design, Setting, and Participants The study is a retrospective analysis of 346 MRKH patients treated in the University Hospital in Tuebingen between 1998 and 2013. Main Outcome Measures The dataset was screened for typical associated malformations as well as atypical malformations and abnormal karyotypes. A complete review of the literature was included. Results Among our cohort of 346 patients, we found that 53.2% had MRKH type 1, 41.3% had MRKH type 2, and 5.5% had MURCS syndrome. The group with associated malformations included 57.6% renal, 44.4% skeletal, and 30.8% other malformations. Additionally, we found 2 cases of absent radius syndrome, 3 cases of anal atresia, and 1 patient with oculodentodigital dysplasia, and other atypical malformations. Abnormal karyotypes were found in 5 cases, and 39 siblings and 11 parents had known malformations. Conclusions This study supports the hypothesis that the syndrome has a multifactorial pathogenesis. With the high numbers of associated malformations reported in this study, patients with MRKH syndrome should be regarded as having a complex syndrome. Molecular–genetic analyses in larger numbers of children after surrogacy, twin pregnancies, and familial cases may make it possible to obtain further information about the etiology of the syndrome.

Klippel-Feil syndrome is a highly heterogeneous complex skeletal disorder characterized by the con genital fusion of two or more cervical vertebrae. The classic clinical triad consists of a short neck, low hairline, and neck movements limitation. The associated mutations are located in the loci of the GDF3 gene (chromosome 12p13.31), GDF6 (chromosome 8q22.1), and MEOX1 (chromosome 17q21.31).To describe the clinical-radiological findings and pedigree of a patient with Klippel-Feil syndrome.A 5-year-old patient with short neck, low posterior hairline, and limitation of lateral movements. The cervical flexion and extension radiographs showed fusion blocks between C1-2-3, C4-5, and C6-7. The chest CT scan showed multiple hemivertebrae in the upper third of the thoracic vertebrae corresponding to ribs I-IV. The karyotype was normal, 46, XX. Reduced penetrance was present in five of the family members. The fusion of C2-3 was present in four members and one individual had low fusion in C5-6. Three of the five affected individuals had a fusion between the capitate and the hamate bone.The malformation of congenital vertebral segmentation is a case of interest since it is an uncommon diagnosis in the pediatric age and whose clinical suspicion can be generated from the clinical examination, radiological study com plemented with the pedigree interpretation in Mendelian inheritance disorders, allowing to provide opportunely genetic counseling to the family.

Klippel-Feil syndrome (KFS) is defined as congenital fusion of two or more cervical vertebrae resulting from a segmentation failure in the developing spine. According to Samartzis et al., the most commonly fused segments are found at C2/3 (74.1%) and C6/7 (70.4%). In patients with C2/3 fusion, especially when there is additional C1 occipitalization, several secondary anomalies including atlantoaxial dislocation (AAD), basilar invagination (BI), Chiari malformation, and syringomyelia can be identified. In this report, we present a case of a 12-year-old patient with C2/3 and occipitalization and a “Full-Spectrum” presentation of associated CVJ abnormalities including C0/1 fusion, AAD, BI, Chiari malformation, syringomyelia, myelopathy and cranial neuropathy received neurological decompression of the cervico-medullary junction by posterior reduction of the AAD and reconstruction of her CVJ using an unconventional hybrid construct due to a high-riding right vertebral artery in C2. To our knowledge, her “Full-Spectrum” presentation may include the most categories of concomitant abnormalities in the literature. In addition, She received neurological decompression of the cervico-medullary junction using an unconventional hybrid construct due to a high-riding vertebral artery in C2. Three months after the surgery, all of her symptoms recovered significantly. Neither Chiari malformation nor syringomyelia could be identified by MRI two years after the surgery. At the last follow-up (4 years), the patient became completely asymptomatic.

Rationale: Patients with Klippel–Feil syndrome (KFS) are always anomaly associated with vertebrobasilar dysplasia. That may present commonly as infarction of brainstem, medulla, and cerebellum. In this article, we reported a rare case of lateral medullary infarction (LMI) with similar features of Brown Sequard syndrome caused by vertebrobasilar dysplasia and KFS, and the 2 rare conditions that are causally related. The case is being reported because of its unusual and rare presentation. Patient concerns: A 38-year-old female presented with acute unsteadiness, along with a tendency to lean to the left side while walking or sitting, and paresthesia in the right lower limb and trunk, at 2 days before admission. She had no history of hypertension and diabetes, but had a 20 years history of neck pain and dizziness, which was related to head movement. Diagnoses: Brown Sequard syndrome and a lesion of the left thoracic spinal cord were suspected initially. KFS was confirmed by the cervical magnetic resonance imaging (MRI) and computed tomographic angiography (CTA) results. Transcranial Doppler (TCD) results confirmed that there was a causal link between LMI and KFS. Interventions: The patient rejected the operation of stabilization of the cervical spine with fusion at appropriate levels. Outcomes: No recurrence of stroke, but neck pain and dizziness remained after 6 months of discharge. Lessons: For such patients, the conventional treatment of cerebral infarction might be ineffective, but stabilization of the cervical spine with fusion at appropriate levels can successfully prevent further episodes of syncope and stroke.

Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. © 2015 Wiley Periodicals, Inc.

We present the first described case of cervical vertebral fusion associated with anterior meningocele and syringomyelia. A 45-year-old woman presented with minor trauma, and plain cervical spine radiographs highlighted a congenital deformity of the cervical vertebral bodies. She had a normal neurological examination; however, further imaging revealed a meningocele and syringomyelia. This case highlights the importance of thorough imaging investigation when presented with a congenital deformity in order to detect and prevent development of degenerative spinal cord pathologies.

Congenital craniocervical segmentation anomaly associated with malalignment of the odontoid process causes progressive spinal cord compression with myelopathy. Recent literatures have reported that ventral decompression could be achieved with posterior craniocervical realignment through posterior instrumented reduction. The purpose of the present study is to show the efficacy of intraoperative electrophysiological monitoring during craniocervical realignment through screws and rod system for congenital craniocervical segmentation anomaly. Consecutive ten patients with a congenital craniocervical segmentation anomaly and myelopathy due to a malaligned odontoid process, who underwent posterior craniocervical realignment, were included. Klippel–Feil syndrome (KFS) was combined in four patients. Gait disturbance and motor weakness were the main presentation. Craniocervical realignment was achieved by intraoperative distraction through a rod and screw system. Intraoperative neuromonitoring was performed with transcranial motor-evoked potential (TcMEP) and somatosensory-evoked potential (SSEP). Significant change in TcMEP occurred in two patients with KFS during surgery, but the change was reversed with release of distraction. All patients were awakened without neurological deficit. Motor weakness and gait disturbance were normalized within 6 months in all patients. Postoperative computed tomography scan and/or magnetic resonance imaging showed that the reduction was complete in all patients. Craniocervical realignment through screws and rod system may be safe and efficacious surgical technique for the treatment of congenital craniocervical anomaly with the help of intraoperative neuromonitoring. However, distraction should be cautiously monitored, especially when Klippel–Feil syndrome is combined.

We present the case of a 34-year-old woman with Klippel-Feil syndrome who developed progressive generalized dystonia of unclear etiology, resulting in intractable pain despite aggressive medical and surgical interventions. Ultimately, palliative sedation was required to relieve suffering. Herein, we describe ethical considerations including defining sedation, determining prognosis in the setting of an undefined neurodegenerative condition, and use of treatments that concurrently might prolong or alter end-of-life trajectory. We highlight pertinent literature and how it may be applied in challenging and unique clinical situations. Finally, we discuss the need for expert multidisciplinary involvement when implementing palliative sedation and illustrate that procedures and rules need to be interpreted to deliver optimal patient-centered plan of care.

We report on a father and his two daughters diagnosed with Klippel–Feil syndrome (KFS) but with craniofacial differences (zygomatic and mandibular hypoplasia and cleft palate) and external ear abnormalities suggestive of Treacher Collins syndrome (TCS). The diagnosis of KFS was favored, given that the neck anomalies were the predominant manifestations, and that the diagnosis predated later recognition of the association between spinal segmentation abnormalities and TCS. Genetic heterogeneity and the rarity of large families with KFS have limited the ability to identify mutations by traditional methods. Whole exome sequencing identified a nonsynonymous mutation in POLR1D (subunit of RNA polymerase I and II): exon2:c.T332C:p.L111P. Mutations in POLR1D are present in about 5% of individuals diagnosed with TCS. We propose that this mutation is causal in this family, suggesting a pathogenetic link between KFS and TCS. © 2014 Wiley Periodicals, Inc.

Klippel–Feil syndrome (KFS) has a classical triad that includes short neck, low hair line and restriction in neck motion and is among one of the congenital causes of difficult airway. Herein, we present a 26-day, 3300 g newborn with KFS who was planned to be operated for correction of an intestinal obstruction. She had features of severe KFS. Anesthesia was induced by inhalation of sevoflurane 2–3% in percentage 100 oxygen. Sevoflurane inhalation was stopped after 2 min. Her Cornmack Lehane score was 2 and oral intubation was performed with 3.5 mm ID non-cuffed endotracheal tube in first attempt. Operation lasted for 45 min. Following uneventful surgery, she was not extubated and was transferred to the newborn reanimation unit. On the postoperative third day, the patient died due to hyperdynamic heart failure. This case is the youngest child with Klippel–Feil syndrome in literature and on whom oral intubation was performed. We also think that positioning of this younger age group might be easier than older age groups due to incomplete ossification process. Resumo: A síndrome de Klippel-Feil (SKF) envolve uma tríade clássica que inclui pescoço curto, linha de implantação dos cabelos baixa e restrição do movimento do pescoço e é uma das causas congênitas de via aérea difícil. Apresentamos o caso de uma recém-nascida, de 26 dias, 3.300 g de peso, com SKF, que foi agendada para cirurgia de correção de uma obstrução intestinal. A paciente apresentava características acentuadas da SKF. A anestesia foi induzida com inalação de sevoflurano a 2-3% em 100% de oxigênio. A inalação de sevoflurano foi interrompida após dois minutos. O escore de Cormack-Lehane da paciente era 2 e a intubação orotraqueal foi feita na primeira tentativa, com tubo endotraqueal de 3,5 mm ID sem balão. O tempo de cirurgia foi de 45 minutos. Após a cirurgia sem intercorrências, a paciente foi transferida para a unidade de reanimação neonatal ainda intubada. No terceiro dia de pós-operatório, foi a óbito por causa de uma insuficiência cardíaca hiperdinâmica. Esse caso apresenta a criança mais jovem com síndrome de Klippel-Feil na literatura e na qual a intubação orotraqueal foi feita. Acreditamos também que o posicionamento de pacientes dessa faixa etária mais jovem pode ser mais fácil do que o de pacientes de faixas etárias mais altas, por causa do processo de ossificação incompleto. Keywords: Neonatal, Difficult airway, Congenital anomalies, Congenital heart disease, Surgery, Critical care, Palavras-chave: Neonatal, Vias aéreas difícil, Anormalidadeas congênitas, Doença cardíaca congênita, Cirurgia geral, Cuidados intensivos

Study Design Cross-sectional study. Objective To determine the prevalence of KFS in asymptomatic patients in New York State. Summary of Background Data Klippel-Feil syndrome (KFS) is characterized by congenitally fused cervical vertebrae and may not be diagnosed clinically because most patients do not have the classic triad of short neck, low posterior hairline, and decreased neck range of motion. KFS may be associated with abnormalities such as congenital scoliosis and deafness, and patients are at higher risk for neurologic injury following cervical spine trauma. The prevalence of KFS has not been evaluated in a large series but is estimated to occur every 40,000 births. Methods A total of 3,534 cervical computed tomography (CT) scans at the emergency department of a level I trauma center were obtained during a one-year period. Duplicate scans and outside hospital imaging were excluded, resulting in 2,917 cervical CT scans for review. Demographic information was collected, and if KFS was present, level(s) fused, Samartzis classification type, and presence of cervical scoliosis and cervical spine fractures were recorded. Results The prevalence of KFS was 0.0058% (1 in 172). Of the 17 subjects with KFS, 8 were female and 9 were male. The most commonly fused levels were C5–C6 and C2–C3. All 17 subjects were classified as Samartzis type I, with a single congenitally fused cervical segment. None of the subjects had cervical scoliosis or cervical spine fractures. Conclusions The prevalence of KFS in our series is much higher than previously described. Because clinical diagnosis may not be reliable, it is likely that this condition is underreported and may only be found incidentally on imaging. Level of Evidence Level III.

Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in their fusion. The clinical triad of the syndrome consists of short neck, low posterior hairline, and limited neck movement, although fewer than 50 percent of patients demonstrate all three clinical features. The short neck and its immobility and instability present a significant challenge for endotracheal intubation. The purpose of this paper is to describe the management of a 13-year-old patient with KFS, extensive dental caries, and restricted mouth opening using a deep sedation technique in the operating room, which allowed successful completion of dental treatment.

Klippel-Feil syndrome (KFS) is a rare disease characterized by a classic triad comprising a short neck, a low posterior hairline, and restricted motion of the neck due to fused cervical vertebrae. We report repeated anesthetic management for orthognathic surgeries for a KFS patient with micrognathia. Because KFS can be associated with a number of other anomalies, we therefore performed a careful preoperative evaluation to exclude them. The patient had an extremely small mandible, significant retrognathia, and severe limitation of cervical mobility due to cervical vertebral fusion. As difficult intubation was predicted, awake nasal endotracheal intubation with a fiberoptic bronchoscope was our first choice for gaining control of the patient's airway. Moreover, the possibility of respiratory distress due to postoperative laryngeal edema was considered because of the surgeries on the mandible. In the operating room, tracheotomy equipment was always kept ready if a perioperative surgical airway control was required. Three orthognathic surgeries and their associated anesthetics were completed without a fatal outcome, although once the patient was transferred to the intensive care unit for precautionary postoperative airway management and observation. Careful preoperative examination and preparation for difficult airway management are important for KFS patients with micrognathia.

The association between Klippel-Feil syndrome and vertebral artery dissection is quite rare. We report an adult patient with vertebral artery dissection and Klippel-Feil syndrome, to our knowledge only the third reported case of its kind. A 45-year-old woman with a known history of Klippel-Feil syndrome presented with occipital head and neck pain following forced neck extension. Diagnostic cerebral angiography revealed a high grade vertebral artery stenosis, consistent with vertebral artery dissection. Following 6 months of medical management, a repeat diagnostic angiogram revealed complete healing of the vessel. While cervical fusion, as seen in Klippel-Feil syndrome, has previously been shown to cause neurologic injury secondary to hypermobility, the association with vertebral artery dissection is incredibly rare. We hypothesize that this hypermobility places abnormal shear force on the vessel, causing intimal injury and dissection. Patients with seemingly spontaneous vertebral artery dissection may benefit from cervical spine radiography, and this predisposition to cerebrovascular injury strongly suggests further evaluation of vascular injury following trauma in patients with Klippel-Feil syndrome or other cervical fusion as clinically warranted.

Background Congenital fusion of cervical vertebrae, including Klippel-Feil syndrome (KFS), is a suspected risk factor for development of degenerative cervical myelopathy (DCM). We aimed to establish prevalence and degenerative patterns of congenital cervical fusion (CCF) among a global cohort of patients with DCM. Methods Data from 3 prospective DCM studies were merged, including clinical data for 813 patients and imaging for 592 patients. CCF was diagnosed by presence of fused cervical vertebrae without signs of degenerative fusion. A wasp-waist sign was used to define a KFS subgroup. Characteristics of patients with CCF and the KFS subgroup were compared with the remainder of patients with DCM. Results Twenty-three patients with CCF (14 KFS) were identified, indicating a prevalence of 3.9% (2.4% KFS). Patients with CCF were older ( P = 0.02), had more operated levels ( P = 0.01), had higher rates of ossified posterior longitudinal ligament ( P = 0.02), and demonstrated worse degenerative changes at C3-4, including spinal cord compression ( P = 0.002) and T 2 weighted image T2WI signal hyperintensity ( P = 0.04). Levels adjacent to fusions showed a trend toward increased spinal cord compression ( P = 0.09), with fusions at C3-4 or above showing cord compression below in 9 of 10 patients, fusions at C5-6 or below having cord compression above in 8 of 8 patients, and fusions at C4-5 showed cord compression above and below in 2 of 2 patients. Conclusions The prevalence of CCF and KFS is higher in DCM than for the general population, suggesting that these patients are predisposed to DCM development. Patients with CCF also have an altered pattern of degenerative changes, seemingly related to adjacent segment degeneration that preferentially affects midcervical levels.

Klippel-Feil syndrome is defined by congenital fusion of two or more cervical vertebrae and can be associated with abnormalities in multiple systems. Management poses challenges to the anesthesiologist, particularly in pregnancy. Cervical spine immobility and instability can make the management of the airway fraught with danger and vertebral column distortion may make neuraxial anesthesia unreliable. We present the management of a nulliparous patient with features consistent with Type I Klippel-Feil syndrome undergoing elective cesarean delivery. The patient had a potentially difficult airway and features consistent with an unstable cervical spine and severe thoracic and lumbar scoliosis. A combined spinal-epidural technique was used which initially provided satisfactory anesthesia, but ultimately proved inadequate despite use of the epidural component. Satisfactory anesthesia for surgery was eventually achieved with the addition of an intravenous remifentanil infusion. We review previous case reports discussing anesthetic management of parturients with Klippel-Feil syndrome, and describe the challenges encountered and lessons learned from management of this case.

Background Various combinations of bony and soft tissue anomalies have been described at the craniovertebral junction (CVJ). These include posterior fossa dermoids (with or without dermal sinuses) associated with Klippel-Feil anomalies and dermoids (no previous reports of overlying dermal sinuses) associated with bony anomalies. Patients Two patients with a combination of CVJ anomalies are described. Results Both patients had a posterior fossa dermoid, dermal sinus, and occipitalized C1 arch. Furthermore, one patient had a complex bony CVJ anomaly, and the other had a Klippel-Feil anomaly in addition. The clinical presentation and management are elucidated. Conclusions Patients who present with any one of these lesions need to be evaluated for the existence of other congenital anomalies. These are complex malformations to treat.

We report the case of a female who presented with progressive fusion and an enlargement of the cervical vertebrae. Her cervical deformity gradually progressed with age, and the abnormal bony protrusion into the spinal canal caused myelopathy. We resected the affected vertebrae to decompress the spinal cord and performed combined anterior-posterior spinal fusion. The progression of the spinal deformity and enlargement of vertebrae stopped after surgery. The enlargement of vertebrae in the present case resembled that observed in Proteus syndrome; however, autonomous vertebral fusion has not been reported previously in patients with this condition. Our report may help expand the knowledge on developmental spine disorders.

Background and importance The extracranial venous drainage of the brain is provided mainly by the jugular veins with the variable participation of extrajugular pathways. Clinical presentation Two cases of occipital sinus pericranii (SP) were observed. A 6-year-old girl presented with a progressively enlarging occipital lump; she was otherwise asymptomatic. An 8-year-old boy presented with mild nuchal headache. In the former case, neuroimaging examinations confirmed the diagnosis of SP; in the latter, SP was noticed on magnetic resonance imaging because it was neglected at physical examination. In both subjects, the radiological examination also showed bilateral occlusion of the jugular veins with ventricular dilation and herniation of cerebellar tonsils into the foramen magnum. Conclusion Exceptionally, SP was noticed to represent the main venous drainage of the underlying brain, thereby compensating for the intracranial hypertension due to venous engorgement. Preservation of SP was advised, and any surgical or endovascular treatment was contraindicated.

Dermoid cysts of posterior fossa are uncommon benign lesions. They differ from other lesions found in the infra tentorial compartment by virtue of their associated conditions. Due to their association with dermal sinus tracts, intracranial infection is a potential threat following infection of the cyst. Due to their embryologic origin, these cysts may also be associated with other congenital anomalies. In this article we detail our eleven-year-experience with posterior fossa dermoid cysts in fifteen patients. Despite the morbid presentation with severe life-threatening complications, the overall outcome was excellent. Implications of the various associations are discussed.

Klippel-Feil syndrome, or brevicollis, is a complex congenital disorder caused by the improper segmentation of the cervical vertebrae. The authors present the very rare case of a patient with Klippel-Feil syndrome who presented with an intradural arachnoid cyst at the craniocervical junction. They also examine possible factors contributing to this association. A 46-year-old woman presented with complaints of progressively worsening headaches and dizziness of 18 months' duration. She also demonstrated mild bilateral upper-extremity weakness. Magnetic resonance imaging revealed fused cervical vertebrae and a dorsal intradural arachnoid cyst at the craniocervical junction, extending down to the fourth cervical level. Because of worsening myelopathy and the presence of brainstem compression, the patient underwent surgical excision of the arachnoid cyst, which was approached via a midline posterior suboccipital/upper cervical route. An endoscope was introduced through a gap between the occiput and fused upper cervical vertebrae, and the arachnoid cyst was widely fenestrated. Postoperatively, the patient has remained symptom free for more than 2 years with evidence of good radiological decompression. The authors report a unique association between craniocervical arachnoid cyst and Klippel-Feil syndrome. To their knowledge, no other cases of this association have been reported in the literature. Arachnoid cysts should be part of the differential diagnosis in the presence of worsening myelopathic symptoms or pain in patients with Klippel-Feil syndrome.

Klippel-Feil syndrome (KFS) is a segmentation malformation of the cervical spine; clinically, it manifests as a short neck with reduced mobility and a low posterior hairline. Several genes have been proposed as candidates for KFS when it is present with other associated anomalies, but the genetics of isolated KFS have been difficult to study because of the syndrome’s mostly sporadic occurrence. We describe a multiplex consanguineous family in which isolated KFS maps to a single 17q21.31 locus that harbors a homozygous frameshift deletion in MEOX1; this deletion results in complete instability of the transcript. Direct sequencing of this gene in two siblings from another consanguineous family affected by isolated KFS uncovered another homozygous truncating (nonsense) MEOX1 mutation that also leads to complete degradation of the transcript. This gene encodes a transcription factor with a well-established and nonredundant role in somite development, and homozygous null alleles of Meox1 in mice have a cervical skeletal defect that is remarkably similar to the one we observe in human individuals with MEOX1 mutations. Our data strongly suggest that KFS is the human phenotypic equivalent of the sclerotome polarity defect that results from Meox1 deficiency in mice.

Purpose Proton magnetic resonance spectroscopy (MRspec), one of the very few techniques for in vivo assessment of neuro-metabolic profiles, is often complicated by lack of standard population norms and paucity of computational tools. Methods 7035 scans and clinical information from 4430 pediatric patients were collected from 2008 to 2014. Scans were conducted using a 1.5T ( n =3664) or 3T scanner ( n =3371), and with either a long (144ms, n =5559) or short echo time (35ms, n =1476). 3055 of these scans were localized in the basal ganglia (BG), 1211 in parieto-occipital white matter (WM). 34 metabolites were quantified using LCModel. A web application using MySQL, Python and Flask was developed to facilitate the exploration of the data set. Results Already piloting the application revealed numerous insights. (1), N -acetylaspartate (NAA) increased throughout all ages. During early infancy, total choline was highly varied and myo -inositol demonstrated a downward trend. (2), Total creatine (tCr) and creatine increased throughout childhood and adolescence, though phosphocreatine (PCr) remained constant beyond 200days. (3), tCr was higher in BG than WM. (4), No obvious gender-related differences were observed. (5), Field strength affects quantification using LCModel for some metabolites, most prominently for tCr and total NAA. (6), Outlier analysis identified patients treated with vigabatrin through elevated γ-aminobutyrate, and patients with Klippel-Feil syndrome, Leigh disease and L2-hydroxyglutaric aciduria through low choline in BG. Conclusions We have established the largest MRSpec database and developed a robust and flexible computational tool for facilitating the exploration of vast metabolite datasets that proved its value for discovering neurochemical trends for clinical diagnosis, treatment monitoring, and research. Open access will lead to its widespread use, improving the diagnostic yield and contributing to better understanding of metabolic processes and conditions in the brain.

A patient with Klippel-Feil syndrome had difficulties in inserting and placing an endotracheal tube under general anesthesia. Klippel-Feil syndrome, characterized by cervical vertebral fusion, scoliosis and endocardiosis, is a rare disease. Anesthesiologists should pay attention to management of anesthesia in airway troubles. A 53-year-old woman diagnosed with Klippel-Feil syndrome was scheduled for general anesthesia with intubation. We tried to insert an endotracheal tube using McGRATH MAC, but it was difficult to insert and place the tube. Finally, we managed to insert a 5.5 mm endotracheal tube. The three-dimensional computed tomography (3D-CT) images after the operation, showed tracheal stenosis at the level of the fourth and fifth cervical vertebrae. In cases where airway difficulties are expected, evaluating 3D-CT images might be useful in airway management.