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 investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Heel/surgery* ; Heel Spur/surgery* ; Retrospective Studies ; Calcaneus/surgery* ; Foot Diseases ; Pain ; Endoscopes ; Treatment Outcome

The most reliable and convenient measurement method of tibial posterior slope(TPS) and its biomechanical relationship with posterior cruciate ligament (PCL) are still controversial. For X-ray measurement, it is recommended to use full-length lateral X-ray of the lower extremity in quatrous section, which has advantage of highly repeatable and common in the daily diagnosis and treatment process, but it is only applicable to patients with tibial rotation within 15°. When the rotation exceeds 30°, it is difficult to identify the inner contour of platform and is no applicable. If it is only used for daily diagnosis and treatment evaluation, when tibial rotation angle is less than 15°, lateral knee X-ray also has a certain reference significance, but the accuracy could not meet requirements of higher clinical research. For CT measurement method, it could correct tibial rotation, but using the fitting point to measure tibial posterior slope on three-dimensional CT reconstruction is only applicable to knee joint without degeneration, more osteophyte affects the way of using fitting point to determine the plane of tibia with real tibia platform conformity degree, have some limitations. For measurement of MRI, it could not only correct tibial rotation, but also minimize the effect of osteophytes by using tibial anatomical axis as the reference axis, which is a good measurement method. For the biomechanical relationship between tibial posterior slope and tibial posterior slope, increased tibial posterior slope indirectly alleviates tension of PCL through tibial anterior displacement or directly reduces load on posterior cruciate ligament in tibial osteotomies, suggesting a protective mechanism for tibial posterior slope;in total knee arthroplasty with cruciate ligament preserved, the size of tibial posterior slope will affect roll back mechanism of femur. When affected knee with PCL injury, it should be avoid to release then aggravate injury, and the stress could be alleviated by increasing tibial posterior slope appropriately. There has been no unified conclusion on the range of tibial posterior slope that is most beneficial to PCL. The natural tibial posterior slope is between 7 ° and 10°, which is considered to be the most beneficial to protection of PCL, but further studies are needed according to the differences in patients' bone status, surgical methods and so on.
Arthroplasty, Replacement, Knee/methods* ; Femur/surgery* ; Humans ; Knee Joint/surgery* ; Osteophyte/surgery* ; Posterior Cruciate Ligament/surgery* ; Tibia/surgery*

The human homologue of mouse progressive ankylosis protein(ANKH)is an inorganic pyrophosphate transport regulator,which regulates tissue mineralization by controlling the level of inorganic pyrophosphate.It plays an important role in the pathogenesis and development of bone and joint diseases,such as ankylosing spondylitis,craniometaphyseal dysplasia,and articular cartilage calcification.This review summarizes the progress of research on ANKH and the above-mentioned diseases.
Ankylosis ; Humans ; Hyperostosis ; Hypertelorism ; Joint Diseases ; Mice ; Mutation

Acquired Hyperostosis Syndrome/surgery* ; Humans ; Tonsillectomy

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

Infantile cortical hyperostosis, or Caffey's disease, usually presents with typical radiological features of soft tissue swelling and cortical thickening of the underlying bone. The disease can be fatal when it presents antenatally, especially before a gestational age of 35 weeks. This fatal, premature form of the disease is known to occur in various ethnic groups around the globe, and approximately 30 cases have been reported in English literature. This paper is unique in that it is the first paper to report a lethal form of prenatal-type infantile cortical hyperostosis diagnosed in South Korea. Born at gestational age of 27 weeks and 4 days, the patient had typical features of polyhydramnios, anasarca, hyperostosis of multiple bones, micrognathia, pulmonary hypoplasia, and hepatomegaly. The patient was hypotonic, and due to pulmonary hypoplasia and persistent pulmonary hypertension, had to be supported with high frequency ventilation throughout the entire hospital course. Due to the disease entity itself, as well as prolonged parenteral nutrition, liver failure progressed, and the patient expired on day 38 when uncontrolled septic shock was superimposed. The chromosome karyotype of the patient was normal, 46, XX, and COL1A1 gene mutation was not detected.
Edema ; Ethnic Groups ; Gestational Age ; Hepatomegaly ; High-Frequency Ventilation ; Humans ; Hyperostosis ; Hyperostosis, Cortical, Congenital ; Hypertension, Pulmonary ; Infant, Newborn ; Infant, Premature ; Karyotype ; Korea ; Liver Failure ; Micrognathism ; Parenteral Nutrition ; Polyhydramnios ; Shock, Septic

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

No abstract available.
Exostoses ; Fingers ; Korea

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes a variety of inflammatory bone disorders associated with dermatologic pathology. A 57-year-old female presented with pustulosis on both hands that had persisted for several months. She also had lower back pain without trauma history. On physical examination, tenderness on her lower back and left anterior chest wall pain were found, and claudication was observed. Radiological studies including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT showed endplate lytic changes in her spine, a focal hypermetabolic lesion in a left rib, and costochondral junction. These findings raised doubt on the presence of metastatic bone lesions, and there was no indication for primary cancer after a complete medical checkup. Palmoplantar pustulosis was well controlled by treatment with acitretin. The osteitis associated with SAPHO syndrome usually presents as osteosclerosis, while reports on osteolytic lesions are rare. We report herein a rare case of SAPHO syndrome associated with bone lesions resembling bone metastasis.
Acitretin ; Acne Vulgaris ; Acquired Hyperostosis Syndrome ; Female ; Hand ; Humans ; Hyperostosis ; Low Back Pain ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Metastasis ; Osteitis ; Osteosclerosis ; Pathology ; Physical Examination ; Positron-Emission Tomography ; Ribs ; Spine ; Thoracic Wall