ABSTRACT
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.
Subject(s)
Child , Female , Humans , Male , Cervical Vertebrae , Cohort Studies , Glycoproteins , Klippel-Feil Syndrome/genetics , Mutation , Nuclear Proteins , Radiography , Transcription Factors/geneticsABSTRACT
El síndrome de Klippel-Feil (KFS) es un grupo heterogéneo de malformaciones a nivel vertebral que presentan un componente genético monogénico; se caracteriza por presentar un defecto en la formación o segmentación de las vértebras cervicales, que da como resultado una apariencia fusionada. La tríada clínica consiste en un cuello corto, una línea de implantación baja del cabello y un movimiento limitado del cuello. Presentamos el caso de un paciente masculino de 17 años que manifiesta los hallazgos clínicos y radiológicos de esta anomalía. (AU)
Klippel-Feil syndrome (KFS) is a heterogeneous group of vertebral malformations that presents a monogenic genetic component, characterized by a defect in the formation or segmentation of the cervical vertebrae, which results in a fused appearance. The clinical triad consists of a short neck, a low hairline and a limited movement of the neck. We present the case of a 17 year-old male patient who presented the clinical and radiological findings of this anomaly. (AU)
Subject(s)
Humans , Male , Female , Pregnancy , Adolescent , Adult , Young Adult , Klippel-Feil Syndrome/therapy , Neck/abnormalities , Scoliosis/diagnostic imaging , Antipyretics/therapeutic use , Hearing Loss , Analgesics/therapeutic use , Klippel-Feil Syndrome/etiology , Klippel-Feil Syndrome/genetics , Klippel-Feil Syndrome/diagnostic imaging , Anti-Bacterial Agents/therapeutic useABSTRACT
Se describe el caso de una paciente de 19 años de edad con malformaciones congénitas múltiples propias del Síndrome de Kippel-Feil, con ectrodactilia de dedo medio en mano derecha, y ausencia de vagina con fístula recto vulvar, resuelta quirúrgicamente per prima sin colostomía temoral derivativa. Tratándose de un caso esporádico, se revisaron antecedentes bibliográficos que permiten compararlo con casos similares reportados para su clasificación y determinación de tipo de herencia.