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Results for “EXOSTOSES, MULTIPLE”

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At least 415 records · Page 23Linked to original sources
PubMed2006

Evidence of genetic underexpression in chorionic villi samples of euploid fetuses with increased nuchal translucency at 10-11 weeks' gestation.

OBJECTIVE: To retrospectively investigate whether the genetic profile from chorionic villous sampling (CVS) found in euploid fetuses with increased NT differs from matched controls. STUDY DESIGN: We employed cDNA microarray technology to characterize and compare the gene expression profile of chorionic villous tissues (which encompass the trophoblast and inner mesenchymal core) belonging to four singleton male fetuses with increased NT at 10-11 weeks' gestation. A pool of four normal chorionic villous tissues belonging to four respective fetuses, matched for gestational age and gender, was used as controls. RESULTS: In euploid fetuses, we found several underexpressed genes, possibly involved in mechanisms associated with the abnormal NT thickness. All these genes are likely to belong to the mesenchymal core of the villus that originates from the extraembryonic mesoderm, and thus might be closely representative of the embryonic genetic profile. They include: (1) genes of embryonic development and differentiation such as Endothelin 3 (EDN3) and secreted frizzled-related protein 4 (SFRP4); (2) genes of the extracellular matrix (ECM) metabolism such as tissue inhibitor of metalloproteinase1 (TIMP1), and disintegrin-like and matrix metalloproteinase (MMP) (reprolysin type) with thrombospondin type 1 Motif or ADAMTS2, exostoses (multiple)-like 1 (EXTL1), heparan sulfate (HS) 6-O-sulfotransferase 1 or HS6ST1, fibronectin 1 (FN1) and Integrin Alpha 10 (ITGA10) involved in HS and proteoglycan bio-synthesis, ECM synthesis and cell-matrix adhesion; (3) genes involved in vessel formation and differentiation such as angiogenic factor (VG5Q), and in blood pressure control and muscle contraction, like Endothelin 3 or EDN3 and sarcolemma associated protein (SLMAP). Such lower expressions of the villous tissues might be related to an immature genetic profile of the embryo development as well as abnormal regulation of ECM bio-synthesis and/or improper vessel growth and blood pressure control. Also, the results partially support the theories proposed for NT enlargement such as altered composition of ECM and abnormal/delayed development of the circulatory system. CONCLUSIONS: Abnormal extraembryonic genetic expression is found at 10-11 weeks' gestation in euploid fetuses with increased NT. If both extra- and intraembryonic mesoderms express the same genetic alterations, then microarray analyses on CVS could be used to screen several mesoderm-derivate anomalies.

Case-Control Studies↗
PubMed1983

The proximal tibio fibular joint. An anatomical study with clinical and pathological considerations.

The proximal tibiofibular joint (TFJ) was studied in 489 dry bones and 50 specimens of dissected knees. A marked variability in morphological characteristics was found with frequent osteoarthritic changes. The most common types of joint found were the trochoid and the double trochoid, followed by the plane type. No articular facet could be recognised in 10 dry fibulae and 12 dry tibiae. The inclination of the joint ranged between 5 degrees and 80 degrees. Osteoarthritis of some degree was present in the TFJ joint in 83 fibulae (27%) and 80 tibiae (38%). It was associated with osteoarthritis of the knee joint, especially affecting the medial compartment, in 30% of cases. Osteoarthritis of the TFJ was also found in a case of multiple exostoses and in a specimen with Bejel disease. No correlation could be established between the presence of the 'squating facets' in the distal end of the tibia and the morphological characteristics or pathology of the TFJ. A clinical case of osteoarthritis of the TFJ in a women of 57 is presented, and the differential diagnosis of pain over the lateral aspect of the knee is discussed.

Female↗
PubMed1993

Chronic intoxication by ethane-1-hydroxy-1,1-diphosphonate (EHDP) in a child with myositis ossificans progressiva.

A child with myositis ossificans progressiva was treated for 8 years with ethane-1-hydroxy-1,1-diphosphonate (EHDP) 30-40 mg/kg per day. Latterly he complained of severe, progressive bone and joint pain which made standing and walking almost impossible. A radiographic skeletal survey showed diffuse ricket-like lesions. Withdrawal of EHDP therapy produced substantial improvement in his general condition as well as in the radiographic appearance of the bones. Multiple exostoses were observed in this case and, particularly those around the knees, presented a peculiar morphology. This supports the theory that exostoses originate from a defect of metaphyseal modelling.

Adolescent↗
PubMed2005

Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletogenesis.

Syndecans are single-pass integral membrane components that serve as co-receptors for growth factors and cytokines and can elicit signal transduction via their cytoplasmic tails. We review here previous studies from our groups on syndecan-3 biology and function in the growth plates of developing long bones in chick and mouse embryos. Gain- and loss-of-function data indicate that syndecan-3 has important roles in restricting mitotic activity to the proliferative zone of growth plate and may do so in close cooperation and interaction with the signaling molecule Indian hedgehog (IHH). Biochemical and protein-modeling data suggest a dimeric/oligomeric syndecan-3 configuration on the chondrocyte's cell surface. Analyses of embryos misexpressing syndecan-3 or lacking IHH provide further clues on syndecan-3/IHH interdependence and interrelationships. The data and the conclusions reached provide insights into mechanisms fine-tuning chondrocyte proliferation, maturation, and function in the developing and growing skeleton and into how abnormalities in these fundamental mechanisms may subtend human congenital pathologies, including osteochondromas in hereditary multiple exostoses syndrome.

Animals↗
PubMed2003

Osteochondroma in the lumbar spinal canal causing sciatic pain: report of two cases.

A search of the English-language medical literature found only two cases in which expansion of an osteochondroma into the lumbar spinal canal caused sciatica. We report another two cases of spinal nerve root compression by solitary lumbar spinal canal osteochondromas: in a 56-year-old man and a 55-year-old woman with no history of hereditary multiple exostoses. Osteochondromas compressing the spinal nerve root were seen at the inferior articular processes of the lumbar vertebrae by computed tomography (CT), three-dimensional reconstruction of CT scans, myelography, and magnetic resonance imaging. The symptoms disappeared after surgical removal of the lesions. Histopathologic examination confirmed the diagnosis of benign osteochondroma.

Female↗
PubMed1986

Exostosis as a cause of spinal cord compression.

A patient harboring multiple hereditary exostoses with a long-lasting tetraparesis owing to intraspinal osteochondroma is described. The results of surgical treatment were poor in contrast to the results achieved by other previous authors performing decompression of the spinal cord. The related literature is briefly reviewed and conclusions are drawn in favor of computed tomographic examination of the spine of patients with vertebral complaints.

Adult↗
PubMed1993

Biologic and clinical significance of cytogenetic and molecular cytogenetic abnormalities in benign and malignant cartilaginous lesions.

Cartilaginous neoplasms are often histologically and therapeutically challenging. Predicting biologic behavior can be difficult. In this study, 120 nonneoplastic, benign, and malignant cartilaginous lesions from 103 patients were cytogenetically analyzed in a 6-year period after short-term culture. For selected cases, fluorescent in situ hybridization (FISH) techniques using chromosome-specific probes were performed on metaphase/interphase preparations and on paraffin-embedded tissue sections. Clonal abnormalities of chromosomes 2, 3, 5, 7, 8, and 12 were most frequently observed. Involvement of chromosomes 5, 8, and 12 may be etiologically significant because of the gene localizations for the human cartilage link protein, Langer-Giedion syndrome (a rare syndrome characterized by multiple exostoses), and type II collagen (a major component of normal cartilage) respectively, to these three chromosomes. That chromosome 7 abnormalities were observed only in malignant tumors is of diagnostic value. The identity of three marker chromosomes and the significance of trisomy 7 (a finding of controversial meaning), were determined with FISH. That the presence of chromosome aberrations and increasing histologic grade strongly correlated (p = 0.001) is of prognostic importance. Moreover, complex aberrations were observed nearly exclusively in high-grade tumors (p = 0.001). The data show that nonrandom chromosome loci are aberrantly affected in cartilaginous lesions and that these abnormalities may be of significant histopathogenetic consequence. In addition, these chromosome abnormalities appear to be diagnostically and prognostically valuable in classifying and grading chondromatous neoplasms.

Adult↗
PubMed1991

Distraction lengthening of the forearm.

Seven patients aged six to 25 underwent progressive distraction lengthening of the forearm. Five had lengthening of the ulna and two of the radius. Four cases had multiple exostoses, two had post-traumatic distal epiphyseal arrests and one had dyschondrosteosis. Two methods were used: the Wagner technique of diaphyseal distraction and bone grafting, or diaphyseal corticotomy and callus distraction without bone grafting. The average lengthening achieved was 3 cm. Review after one to three year's follow-up showed satisfactory improvement in appearance and function in all cases, with minimal complications.

Adolescent↗
PubMed1987

An unusual case of diaphyseal aclasis arising in fingers.

Diaphyseal aclasis (multiple hereditary exostoses) occurs in the bones developed in cartilage and gives rise to cartilage-capped exostoses. It usually affects the ends of the diaphyses of long bones of extremities (McKusick, 1972). Although the phalanges of the fingers may be shorter than normal, no record could be found of significant deformity. A case of digital deformity is described below.

Child, Preschool↗
PubMed2005

Pseudoaneurysm associated with multiple osteochondromatosis.

The authors present a case of a 12-year-old boy with a known family history of multiple hereditary exostoses who presented with knee swelling. Physical examination and subsequent workup revealed a pseudoaneurysm associated with an osteochondroma. We present this interesting case and review the literature.

Aneurysm, False↗
PubMed2002

Cytogenetic and molecular cytogenetic evidence of recurrent 8q24.1 loss in osteochondroma.

Osteochondroma most frequently arises sporadically and as a solitary lesion, but may also arise as multiple lesions characterizing the autosomal dominant disorder hereditary multiple exostoses (HME) and the contiguous gene-deletion syndrome, Langer-Giedion syndrome (LGS). Various germline mutations of two putative tumor suppressor genes, EXT1 localized to 8q24.1 and EXT2 localized to 11p11 approximately p12, have been demonstrated in HME families. Constitutional chromosomal deletions or structural rearrangements of 8q24.1 are seen in LGS. Cytogenetic reports of sporadic and hereditary osteochondromas are few, but have revealed loss or structural rearrangements of 8q24.1 in a small number of tumors. In the current study, karyotypic evaluation of 37 osteochondroma specimens (both sporadic and hereditary lesions) revealed chromosomal anomalies of 8q24.1 in 10 specimens (27%). In an effort to determine the presence and frequency of submicroscopic deletions, molecular cytogenetic studies were performed on this same set of tumors utilizing a chromosome 8 specific centromeric probe and an 8q24.1 cosmid probe (locus D8S51, within the minimal LGS deletion region). Loss of the 8q24.1 locus was detected by fluorescence in situ hybridization in 27 of 34 (79%) osteochondroma specimens analyzed including all 10 specimens exhibiting chromosome 8 abnormalities cytogenetically. These findings indicate that a significant subset of osteochondromas harbor genetic aberrations at the EXT1 locus and suggest that loss or mutation of EXT1 plays an important role in the pathogenesis of sporadic as well as hereditary osteochondromas.

Adolescent↗
PubMed2000

Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics.

While it has been long appreciated that sugar-modified proteins coat the cell surface, their functions are poorly understood. Here, I describe recent genetic studies that demonstrate that one class of sugar-modified proteins, cell-surface proteoglycans, play crucial roles in morphogenesis, growth regulation and tumor suppression. Mutations that affect individual proteoglycans or the enzymes required for glycosaminoglycan synthesis regulate Wingless and Decapentaplegic signaling in Drosophila, and body size in mice and humans. Compromising proteoglycan function is also associated with the development of Wilm's tumors and hereditary multiple exostoses. In this review, these biological findings are placed in the context of proteoglycan biochemistry and molecular function.

Animals↗
PubMed2001

Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects.

Inherited defects of skull ossification often manifest as symmetric parietal foramina (PFM; MIM 168500). We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity. Deletions of 11p11-p12 (proximal 11p deletion syndrome, P11pDS; MIM 601224) are characterized by multiple exostoses, attributable to haploinsufficiency of EXT2 and PFM. Here we identify ALX4, which encodes a paired-related homeodomain transcription factor, as the PFM disease gene in P11pDS.

Animals↗
PubMed1999

Diaphyseal aclasis affecting the temporomandibular joint.

Diaphyseal aclasis is a rare disorder of bone development in which multiple, cartilagenous exostoses develop and enlarge mainly on the ends of long bones. It has also been described in the vertebral column where it may give rise to spinal cord compression but has not previously been reported as occurring in the jaws. A case is reported in which a patient known to suffer from diaphyseal aclasis at many other anatomical sites displays temporomandibular joint changes which are highly suggestive of the disease now manifesting in the jaws. The presentation, investigations and treatment are described and the literature concerning previous cases of diaphyseal aclasis is reviewed.

Adolescent↗
PubMedDate not supplied

[Intra-acetabular localisation of an osteochondroma causing subluxation of the hip joint].

INTRODUCTION: Intra-acetabular localisation of an osteochondroma causing subluxation of the hip joint is a rare entity in children suffering from multiple hereditary exostoses. In literature only 6 operatively treated cases have been reported. CASE: We add the case of an 8-year-old boy with an intraarticular exostosis of the left acetabulum causing subluxation of the hip. Using an anterolateral approach to the hip joint this exostosis was removed surgically together with some extraarticular exostoses of the proximal femur. The hip could be re-centered in combination with an additional varus derotation osteotomy of the proximal femur. Intraoperatively the femoral head was only subluxated to minimise the risk of avascular necrosis. After a follow-up of two years the patient has complete remission of symptoms and there is no evidence of avascular necrosis radiologically with good remodelling of the left hip. CONCLUSION: The operative treatment of an intraarticular exostosis of the hip joint is a difficult and risky surgical procedure. The reported open surgical procedure allowed resection of the intraarticular exostosis in combination with therapy of additional pathologies of the proximal femur.

Acetabulum↗
PubMed2001

Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode alpha 1,4- N-acetylglucosaminyltransferases that likely are involved in heparan sulfate/ heparin biosynthesis.

The tumor suppressors EXT1 and EXT2 are associated with hereditary multiple exostoses and encode bifunctional glycosyltransferases essential for chain polymerization of heparan sulfate (HS) and its analog, heparin (Hep). Three highly homologous EXT-like genes, EXTL1-EXTL3, have been cloned, and EXTL2 is an alpha1,4-GlcNAc transferase I, the key enzyme that initiates the HS/Hep synthesis. In the present study, truncated forms of EXTL1 and EXTL3, lacking the putative NH2-terminal transmembrane and cytoplasmic domains, were transiently expressed in COS-1 cells and found to harbor alpha-GlcNAc transferase activity. EXTL3 used not only N-acetylheparosan oligosaccharides that represent growing HS chains but also GlcAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl (Cbz), a synthetic substrate for alpha-GlcNAc transferase I that determines and initiates HS/Hep synthesis. In contrast, EXTL1 used only the former acceptor. Neither EXTL1 nor EXTL3 showed any glucuronyltransferase activity as examined with N-acetylheparosan oligosaccharides. Heparitinase I digestion of each transferase-reaction product showed that GlcNAc had been transferred exclusively through an alpha1,4-configuration. Hence, EXTL3 most likely is involved in both chain initiation and elongation, whereas EXTL1 possibly is involved only in the chain elongation of HS and, maybe, Hep as well. Thus, their acceptor specificities of the five family members are overlapping but distinct from each other, except for EXT1 and EXT2 with the same specificity. It now has been clarified that all of the five cloned human EXT gene family proteins harbor glycosyltransferase activities, which probably contribute to the synthesis of HS and Hep.

Adult↗