Surgery of a Klippel-Feil malformation of the cervicothoracic junction.
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ABSTRACT:
SUBMITTER: Boos N
PROVIDER: S-EPMC7571472 | biostudies-literature | 2009 Aug
REPOSITORIES: biostudies-literature
Publications
Surgery of a Klippel-Feil malformation of the cervicothoracic junction.
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 20090801 8
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| S-EPMC7571469 | biostudies-literature
Project description:Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.
| S-EPMC3631233 | biostudies-literature
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| S-EPMC6353332 | biostudies-literature
Project description: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, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D. 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.
| S-EPMC7149842 | biostudies-literature
Project description: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.
| S-EPMC3542464 | biostudies-literature
Project description:BackgroundKlippel-Feil syndrome (KFS) is characterized by the developmental failure of the cervical spine and has two dominantly inherited subtypes. Affected individuals who are the children of a consanguineous marriage are extremely rare in the medical literature, but the gene responsible for this recessive trait subtype of KFS has recently been reported.ResultsWe identified a family with the KFS phenotype in which their parents have a consanguineous marriage. Radiological examinations revealed that they carry fusion defects and numerical abnormalities in the cervical spine, scoliosis, malformations of the cranial base, and Sprengel's deformity. We applied whole genome linkage and whole-exome sequencing analysis to identify the chromosomal locus and gene mutated in this family. Whole genome linkage analysis revealed a significant linkage to chromosome 17q12-q33 with a LOD score of 4.2. Exome sequencing identified the G > A p.Q84X mutation in the MEOX1 gene, which is segregated based on pedigree status. Homozygous MEOX1 mutations have reportedly caused a similar phenotype in knockout mice.ConclusionsHere, we report a truncating mutation in the MEOX1 gene in a KFS family with an autosomal recessive trait. Together with another recently reported study and the knockout mouse model, our results suggest that mutations in MEOX1 cause a recessive KFS phenotype in humans.
| S-EPMC3849745 | biostudies-literature
Project description:This is the first case description of the association of Klippel-Feil Syndrome (KFS), Tourette Syndrome (TS), Motor Stereotypies, and Obsessive Compulsive Behavior, with chromosome 22q11.2 Duplication Syndrome (22q11DupS). Neuropsychiatric symptoms in persons with 22q11.2 deletion, including obsessive compulsiveness, anxiety, hyperactivity, and one prior case report of TS, have been attributed to low copy number effects on Catechol-O-Methyltransferase (COMT). However, the present unique case of 22q11DupS and TS suggests a more complex relationship, either for low- or high-COMT activity, or for other genes at this locus.
| S-EPMC2797364 | biostudies-literature
Project description:BackgroundNeural tube defect (NTD) is a common birth defect causing much death in the world. Variants in VANGL1 lead to NTD and caudal regression syndrome. NTD displays a complex phenotype encompassing both genetic and environmental factors.MethodsThe fetus was diagnosed by prenatal ultrasound examination. Postnatal CT and autopsy were performed. Genetic testing was conducted in the family and Sanger sequencing was validated. Multiple prediction soft-wares were used to predict the pathogenicity of the variant.ResultsThe VANGL1 gene variant c.1151C>G (P384R) was detected in a fetus diagnosed with tethered spinal cord and sacrococcygeal lipoma. The VANGL1 variant c.1151C>G (P384R) was reported in a Klippel-Feil syndrome patient. The VANGL1 variant was validated in the trio-family but the mother showed no abnormalities.ConclusionOverall, this study presents fetal NTD caused by the same VANGL1 variant found in a Klippel-Feil syndrome patient with complete clinical information of prenatal ultrasound, postnatal CT, and genetic results as early as 25 GW. Our study not only expands the VANGL1 mutational spectrum but also sheds light on the important role of the VANGL1 P384R variant in human development.
| S-EPMC8372072 | biostudies-literature
Project description:Importance:Children with Klippel-Feil syndrome (KFS), characterized principally by abnormal fusion of 2 or more cervical vertebrae, may have many additional congenital anomalies. The overall prevalence of otolaryngologic manifestations among patients with KFS has not been previously characterized. Objective:To define the otolaryngologic diagnoses made and procedures performed in 95 patients with KFS, which, to our knowledge, is the largest series of this challenging patient population published to date. Design, Setting, and Participants:For this retrospective review, all patients with KFS who underwent otolaryngology consultation at our institution over a 26-year period (January 1989 to December 2015) were included. Patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes and were confirmed through individual medical record review. Relevant otolaryngologic diagnoses and procedures were extracted using ICD-9 and Current Procedural Terminology codes, respectively. Selected demographics included age, sex, number of clinic visits, and number of procedures. Main Outcomes and Measures:The primary outcomes were the otolaryngologic diagnoses and procedures associated with the KFS patient population; the secondary outcome was Cormack-Lehane classification documented during airway procedures. Results:Overall, 95 patients with KFS were included in this study (55 males [58%] and 40 females [42%]); mean (range) age at time of presentation to the otorhinolaryngology clinic was 5.8 (birth-23.0) years. Each patient with KFS averaged 8 visits to the otorhinolaryngology office and 5 otolaryngologic diagnoses. The most common diagnosis was conductive hearing loss (n?=?49 [52%]), followed by sensorineural hearing loss (n?=?38 [40%]), and dysphagia (n?=?37 [39%]). Sixty-two (65%) patients underwent otolaryngologic procedures, with 44 (46%) undergoing multiple procedures. The most common procedure was tympanostomy tube placement (n?=?36 [38%]), followed by office flexible endoscopy (n?=?23 [24%]). Twelve of the 20 patients who underwent direct laryngoscopy had documented Cormack-Lehane classification; 5 of 12 patients (42%) had a compromised view (grade 2, 3, or 4) of the larynx. Three patients required tracheotomies at this institution for airway stabilization purposes; each had severe upper airway obstruction leading to respiratory failure. Conclusions and Relevance:Patients with KFS require consultation for a variety of otolaryngologic conditions. Among these, hearing loss is the most common, but airway issues related to cervical spine fusion are the most challenging. Formulating an appropriate care plan in advance is paramount, even for routine otolaryngology procedures.
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Project description:This study aimed to assess the feasibility and safety of robot-assisted thoracic surgery (RATS) for resecting benign tumors of the cervicothoracic junction. Between 2017 and 2021, a total of 54 patients with benign cervicothoracic junction tumors were included. Among them, 46 underwent RATS while 8 underwent open surgery. Using a propensity score based on four variables (age, sex, comorbidity, and tumor size). The outcomes compared included short-term outcomes such as blood loss, as well as long-term outcomes including respiratory function and patients' postoperative health-related quality of life. No operative deaths occurred in this study. RATS was associated with less intraoperative blood loss (102 < 380 ml, P = 0.001) and a shorter length of hospital stay (1.8 < 4.8, P < 0.001). After a median follow-up of 37 months, no recurrences were reported, and no statistically significant differences were found in the 3-year survival between the two groups. The postoperative respiratory function of patients with open surgery showed a significant decrease compared to preoperative levels and were lower than those of RATS patients. In terms of health-related quality of life, RATS was associated with a better mean EQ-5D-5L index than open surgery (0.808 > 0.650, P < 0.05). In RATS, tumor sizes > 5 cm (mean ± SD = 0.768 ± 0.111, P = 0.028) and neurogenic tumors (mean ± SD = 0.702 ± 0.082, P < 0.001) remained significantly and independently associated with a lower EQ-5D-5L index. This study demonstrated that robot-assisted thoracic surgery for benign tumors of the cervicothoracic junction is a safe and technically feasible procedure, particularly for tumors < 5 cm and non-neurogenic tumors.
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