OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

Cervical Vertebrae ; Exostoses, Multiple Hereditary ; Humans ; Spinal Cord Compression ; Spinal Osteophytosis

A female patient who underwent total knee arthroplasty presented with a snapping sensation over the left knee at 10 years postoperatively. Initially, the bony mass was visible on the medial femoral condyle radiographically at 5 years postoperatively. The mass had enlarged over time and her symptoms were progressive. The mass was excised at postoperative 18 years and confirmed as an osteochondroma histopathologically. The patient’s symptoms have been completely resolved for 3-year follow-up after excision. LEVEL OF EVIDENCE: V
Arthroplasty ; Arthroplasty, Replacement, Knee ; Female ; Follow-Up Studies ; Humans ; Knee ; Osteochondroma ; Sensation

OBJECTIVE: To identify pathogenic variations of EXT1 and EXT2 genes in two Chinese pedigrees affected with hereditary multiple exostosis (HME). METHODS: Genomic DNA was extracted from peripheral blood samples using a phenol-chloroform method. PCR and Sanger sequencing was conducted to amplify the exons and the flanking intronic regions of the EXT1 and EXT2 genes. RESULTS: DNA sequencing has revealed a heterozygous missense variation c.812A>G (p.Tyr271Cys) in the exon 1 of EXT1 in pedigree 1, and a heterozygous frameshift variation c.1431dup (p.Ser478Leufs*43) in the exon 6 of EXT1 in the proband from pedigree 2. Both variations have co-segregated with the disease phenotype, which was also consistent with previous report. CONCLUSION Two heterozygous pathogenic variations underlying HME have been identified. The result has facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.
Asian Continental Ancestry Group ; Base Sequence ; DNA Mutational Analysis ; Exostoses, Multiple Hereditary ; genetics ; pathology ; Frameshift Mutation ; Humans ; Mutation, Missense ; N-Acetylglucosaminyltransferases ; genetics ; Pedigree

OBJECTIVE: To detect EXT1 and EXT2 gene mutations in two pedigrees affected with hereditary multiple exostosis (HME). METHODS: The coding regions and exon/intron boundaries of the EXT1 and EXT2 genes were analyzed by targeted next-generation sequencing (NGS). Suspected mutations were confirmed by Sanger sequencing of the probands, their family members and 200 unrelated healthy controls. Gross deletion was confirmed by quantitative PCR (qPCR) analysis and multiple ligation-dependent probe amplification (MLPA) analysis. RESULTS: Two mutations were detected in the pedigrees, which included EXT2 gene c.337_338insG mutation in pedigree 1 and deletion of entire EXT1 in pedigree 2. Analysis of sequencing data revealed that a novel heterozygous mutation (c.337_338insG) in EXT2 gene in proband 1 and his father. The same mutation was not found among healthy family members and 200 unrelated healthy controls. As shown by NGS and MLPA analysis, proband 2 carried a heterozygous deletion of entire EXT1 gene. The same deletion was also found in her mother by qPCR. CONCLUSION Mutations of the EXT1 and EXT2 genes probably underlie the HME in both pedigrees. NGS combined with Sanger sequencing, qPCR and MLPA is effective for attaining the diagnosis.
DNA Mutational Analysis ; Exostoses, Multiple Hereditary ; genetics ; Female ; Humans ; Mutation ; N-Acetylglucosaminyltransferases ; genetics ; Pedigree

OBJECTIVE: To explore the application accuracy of virtual preoperative plan after the condylectomy via intraoral approach under computer assisted surgical navigation, and to analyze the location and cause of the surgical deviation to provide reference for the surgical procedure improvement in the future. METHODS: In the study, 23 cases with condylar hypertrophy (11 with condylar osteochondroma and 12 with condylar benign hypertrophy) in Department of Oral and Maxilloficial Surgery, Peking University School and Hospital of Atomatology from December 2012 to December 2016 were treated by condylectomy via intraoral approach under computer assisted surgical navigation. The patient's spiral CT data were imported into ProPlan software before operation, and the affected mandibular ramus was reconstructed three-dimensionally. The condylar osteotomy line was designed according to the lesion range, and the preoperative design model was generated and introduced into the BrainLab navigation system. Under the guidance of computer navigation, the intraoral approach was used to complete the condylar resection according to the preoperative design of the osteotomy line. Cranial spiral CT of the craniofacial region was taken within one week after operation. three-dimensional reconstruction of the mandibular ramus at the condylectomy side was performed, and the condylar section was divided into six segments (anterolateral, anterior, anteromedial, posteromedial, posterior, and posterolateral) and the corresponding regional measurement points P1 to P6 were defined. Then the preoperative virtual model and the postoperative actual model were matched by Geomagic studio 12.0 to compare the differences and to analyze the accuracy of the operation. RESULTS: All the patients had successfully accomplished the operation and obtained satisfactory results. Postoperative CT showed that the condyle lesion was completely resected, and the condylar osteotomy line was basically consistent with the surgical design. No tumor recurrence or temporomandibular joint ankylosis during the follow-up period. The postoperative accuracy analysis of the condylar resection showed that the confidence intervals measured by the six groups of P1 to P6 were (-2.26 mm, -1.89 mm), (-2.30 mm, -1.45 mm), (-3.37 mm, -2.91 mm), (-2.83 mm, -1.75 mm), (-1.13 mm, 0.99 mm), and(-1.17 mm, 0.17 mm), where P3 group was different from the other 5 groups. There was no significant difference between the P5 and P6 groups and the difference between the other four groups was statistically significant. CONCLUSION Under the guidance of computer navigation, the intraoral approach can be performed more accurately. The surgical deviation of each part of the osteotomy surface is mainly due to excessive resection. The anterior medial area of the anterior medial condyle represents the most excessive resection. The posterior and posterior lateral measurement points represent the posterior condylar area. The average deviation is not large, but the fluctuation of the deviation value is larger than that of the other four groups. The accuracy of computer-assisted subtotal resection has yet to be improved.
Humans ; Mandibular Condyle ; Mandibular Neoplasms ; Neoplasm Recurrence, Local ; Osteochondroma ; Osteotomy ; Tomography, X-Ray Computed

Synovial chondromatosis is an uncommon disorder characterized by cartilaginous proliferation within the synovial membrane of the articular joint. Smaller joints are rarely affected and it may be progressed to osteochondromatosis after ossification or calcification of metaplastic cartilage. It is commonly presented in the third to fourth decade of life, but rarely presented in adolescence. We report a unique case of synovial osteochondromatosis of the subtalar joint in 14-year-old baseball player. Arthroscopic removal of loose body and complete excision of the osteochondral mass with concomitant synovectomy resulted in satisfactory outcome without recurrence at final follow-up.
Adolescent* ; Arthroscopy ; Baseball* ; Cartilage ; Chondromatosis, Synovial* ; Follow-Up Studies ; Humans ; Joints ; Osteochondromatosis ; Recurrence ; Subtalar Joint* ; Synovial Membrane

Osteochondromas develop as cartilaginous nodules in the periosteum of bones. They are the commonest benign tumors of the skeleton, generally observed in the long bones. Rarely, they are also found in the axial skeleton, flat bones of skull and facial bones. During a regular dissection, we came across a solitary osteochondroma in posterior surface of the body of the right pubic bone. Histopathology of the bony projection confirmed the typical features of the osteochondroma. The symptomatic osteochondromas are usually evaluated during radiographic examination. Though, the observed osteochondroma is relatively smaller its unusual location is remarkable and knowledge of occurrence of such nodules is clinically important during the diagnosis and planning of treatment.
Cadaver* ; Diagnosis ; Facial Bones ; Osteochondroma* ; Periosteum ; Pubic Bone* ; Skeleton ; Skull

Hereditary multiple exostosis (HME) is an autosomal dominant disorder manifested by the presence of multiple osteochondromas. Although the lesions are benign in nature, exostoses are often associated with characteristic progressive skeletal deformity and displaying clinical symptoms such as mechanical irritation or impingement. We present the successful arthroscopic resection in a 24-year-old HME male with impingement syndrome and long head tendon tear of the biceps caused by osteochondroma arising from the distal clavicle.
Clavicle ; Congenital Abnormalities ; Exostoses ; Exostoses, Multiple Hereditary ; Head ; Humans ; Male ; Osteochondroma ; Shoulder Impingement Syndrome ; Shoulder ; Tears ; Tendons ; Young Adult