Multiple Osteocondromas (MO). By Judith VMG Bovée

http://www.ojrd.com/content/3/1/3
Multiple osteochondromas
Judith VMG Bovée
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
author email corresponding author email.

Orphanet Journal of Rare Diseases 2008, 3:3doi:10.1186/1750-1172-3-3
The electronic version of this article is the complete one and can be found online at: http://www.ojrd.com/content/3/1/3
Published: 13 February 2008
© 2008 Bovée; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones.
The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1).
Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty.
They are pedunculated or sessile (broad base) and can vary widely in size.
The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18.
The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected.

Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal.
The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%.
MO is an autosomal dominant disorder and is genetically heterogeneous.
In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found.

The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization.
The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas.
If the exact mutation is known antenatal diagnosis is technically possible.

MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints.
Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma.
Patients should be well instructed and regular follow-up for early detection of malignancy seems justified.
For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed.

Disease name and synonyms
Multiple Osteochondromas (MO) MIM 133700
Hereditary Multiple Exostoses (HME), Multiple Hereditary Exostoses (MHE), EXT, diaphyseal aclasis, (multiple hereditary) osteochondromatosis, multiple cartilaginous exostoses

Definition and diagnostic criteria
Osteochondroma (osteocartilaginous exostosis) is a cartilage capped bony projection arising on the external surface of bone containing a marrow cavity that is continuous with that of the underlying bone [1].
A diagnosis of MO can be made when radiologically at least two osteochondromas of the juxta-epiphyseal region of long bones are observed. In the majority of patients a positive family history and/or mutation in one of the EXT genes can be detected [2,3].

Epidemiology
The prevalence of MO is estimated at 1:50,000 persons within the general population [4] and seems to be higher in males (male-to-female ratio 1.5:1) [2,5].
This is probably due to the fact that females tend to have a milder phenotype and are therefore more easily overlooked [2].
The solitary (sporadic) form of osteochondroma is approximately six times more common than the occurrence within the context of MO.
Approximately 62% of the patients with multiple osteochondromas have a positive family history [2].

Clinical description
Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty.
They are pedunculated or sessile (broad base) and can vary widely in size.
The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee (Figures 1 and 2A).
The facial bones are not affected.
The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18 [6].

In addition, in MO patients a variety of orthopaedic deformities can be found like deformities of the forearm (shortening of the ulna with secondary bowing of radius) (39–60%) [4,6,7]
(Figure 2C), inequality in limb length (10–50%) [4,7],
varus or valgus angulation of the knee (8–33%) [4,7],
deformity of the ankle (2–54%) [4,7] and disproportionate short stature (37–44%) [2,5,6].
Figure 1. Photograph of the legs of a 26 year old male showing multiple lumps leading to deformity.
Figure 2. Examples of radiographs demonstrating multiple osteochondromas around the knee (A) and at the pelvis and proximal femur (B), while (C) demonstrates the deformity of the forearm (shortening of the ulna with secondary bowing of radius) that is found in 39–60% of the patients.

Other complications of the osteochondromas include osseous and cosmetic deformities, bursa formation, arthritis (14%) [5] and impingement on adjacent tendons, nerves (22.6%) [5], vessels (11.3%) [5] or spinal cord (0.6%) [5,8].
MO patients may have abnormal scar formation [9]. Osteochondromas bear the risk for fracture of the bony stalk during physical exercise. This is estimated to occur in approximately 5% of osteochondromas [10] and may be reason for surgical removal.

The majority of MO patients experiences pain [11,12], approximately half of which concerns generalised pain [11].
Therefore, the number of MO individuals having pain has been underestimated and pain seems a problem that must be addressed when caring for MO patients.
The occurrence of pain was associated with MO related complications and surgery [11].

The most important complication of MO is malignant transformation of an osteochondroma, which is estimated to occur in 0.5–5% of patients [2,4,5,13,14].
Clinical signs of malignant transformation include an increase in size and pain [6].
Malignant transformation of osteochondroma leads to a secondary peripheral chondrosarcoma in 94% of the cases [15].
The suspicion of secondary chondrosarcoma is indicated by growth of the tumour after puberty, the presence of pain, or a thickness over 1 cm of the cartilaginous cap in adults.

Aetiology
Two genes, EXT1 and EXT2 located respectively at 8q24 and 11p11-p12, have been isolated to cause MO [16-19].
Additional linkage to chromosome 19p has been found, suggesting the existence of an EXT3-gene [20].
However, the gene has never been identified. Moreover, the increased sensitivity of mutation detection and the use of new techniques screening for larger deletions, such as MLPA, have dramatically decreased the proportion of MO patients without an EXT1 or EXT2 mutation to <15% name="IDAL050D">[21-23].
These data question the existence of an EXT3-gene at 19p.
The EXT1 gene is composed of 11 exons and has a coding region of 2238 bp [17-24].
The EXT2-gene contains 16 exons [18,19] and its cDNA defines a single open reading frame of 2154 bp.
EXT1 and EXT2 are highly similar, especially in the carboxy terminal region [18,19].
The EXT1 gene was reported to show linkage in 44%–66% of the MO families [25,26], whereas EXT2 would be involved in 27% [26].

Germline mutations of EXT1 and EXT2 in MO patients have been studied extensively in Caucasian as well as Asian populations [27].
In EXT1, mutations are more or less randomly distributed over the first 6 exons, while the last 5 exons, containing the conserved carboxyterminal region, contain significantly less mutations [27]
Similarly, in EXT2 most mutations are found in the first eight exons.

No mutational hotspots are found.
Approximately 80% of the mutations are either non-sense, frameshift, or splice-site mutations leading to premature termination of EXT proteins [25,28-32].
The majority of missense mutations also lead to defective EXT protein function [33].
Mutations in EXT1 seem associated with a more severe phenotype as compared to EXT2 [34-37].
It has long been thought that osteochondromas are the result of skeletal dysplasia. It is now however generally accepted that osteochondromas are neoplastic, since genetic changes are found in the cartilage cap [1,38-42].
The EXT-genes are tumour suppressor genes.
Loss of the remaining EXT1 wildtype allele has been demonstrated in the cartilage cap of osteochondromas from MO patients [39].
However, in a considerable proportion of MO patients loss of the remaining wildtype allele could not be detected so far [43].
In seven out of eight solitary osteochondromas, homozygous deletions of EXT1 are found [38] further supporting the two-hit model. Moreover, the deletions were confined to the cartilage cap.
Thus, the cartilage cap is the clonal neoplastic element, while the stalk is reactive [38].
Both EXT1 and EXT2 mRNA is ubiquitously expressed [17-19].
A high level of expression of Ext1 and Ext2 mRNA has been found in developing limb buds of mouse embryos [44,45] and expression was demonstrated to be confined to the proliferating and prehypertrophic chondrocytes of the growth plate [46].
In osteochondromas and peripheral chondrosarcomas the expression of EXT1 and/or EXT2 is decreased, corresponding to the mutation status [47].

The gene products, exostosin-1 (EXT1) and exostosin-2 (EXT2), are endoplasmic reticulum localized type II transmembrane glycoproteins which form a Golgi-localised hetero-oligomeric complex that catalyzes heparan sulphate (HS) polymerization [48-51].
Heparan sulphate proteoglycans (HSPG) are large macromolecules composed of heparan sulphate glycosaminoglycan chains linked to a protein core.
Four important HSPG families are syndecan, glypican, perlecan and isoforms of CD44 bearing variable exon 3 (CD44v3).

In osteochondromas in which EXT expression is decreased due to mutation or deletion, the heparan sulphate proteoglycans seem to accumulate in the cytoplasm of the cell, instead of being transported to be expressed at the cell surface [47].
EXT and HSPGs are required for high-affinity binding of fibroblast growth factor to its receptor and for the diffusion of the morphogens Hedgehog (Hh, human homologues Indian (IHH) and Sonic Hedgehog (SHH) [52-54], decapentaplegic (dpp, human homologues TGF-beta and BMP) and wingless (wng, human homologue Wnt) [55,56].
These three pathways are important during development and are specifically active in the growth plate during endochondral bone formation.

During normal growth, IHh and PTHLH are involved in a delicate paracrine feedback loop regulating proliferation and differentiation of the chondrocytes of the growth plate (Figure 3).
In osteochondroma, IHH signalling is still active and is probably cell autonomous [57,58]. PTHLH signalling, which is downstream of IHH and is responsible for chondrocyte proliferation, is absent in osteochondroma, while being upregulated upon malignant transformation of osteochondroma [59,60].
Wnt signalling and TGF-beta signalling are also active in the majority of osteochondromas [57]. The exact role of EXT in orchestrating these pathways leading to osteochondroma formation in MO patients needs to be further elucidated.

Figure 3. Growth plate signaling in the normal growth plate. Indian Hedgehog protein (IHh) is expressed in the prehypertrophic cells, and diffuses over a variable distance to its receptor Patched (PTCH).
Subsequently, increased secretion of ParaThyroid Hormone Like Hormone (PTHLH) is induced at the apical perichondrium via an incompletely understood mechanism.

PTHLH then diffuses to its receptor, whose expression is restricted to the late proliferating chondrocytes, inhibiting their further differentiation, resulting in less IHh producing cells, which closes the feedback loop.
Thus, PTHLH regulates the pace of chondrocyte differentiation by delaying the progression of chondrocytes towards the hypertrophic zone, allowing longitudinal bone growth. Defective or absent EXT proteins leading to altered or absent HSPG expression at the cell surface may affect this negative feedback loop by disturbing the diffusion of IHh, produced at the pre-hypertrophic chondrocytes, towards its receptor Ptc.

Diagnostic methods
When a patient is suspected to have MO, the full radiological documentation, histology (if available), patient history and family history have to be carefully reviewed.
Given the specific radiological and histological expertise needed, and the rarity of the disorder and of those in the differential diagnosis, it is recommended that this review is performed by specialists in the field, for instance through a national bone tumour registry consisting of clinicians, radiologists and pathologists.
If this review is indicative for MO, the peripheral blood of the patient may be screened for germline mutations in EXT1 or EXT2 [61].

In case of a positive family history in which MO is clearly established in relatives, the diagnosis of MO can be clinically made and mutation analysis is not essential.
With the currently used methods it is possible to detect point mutations or gross deletions in almost 90% of MO patients [21-23,61-63].

To evaluate possible malignant transformation in case of complaints or growth of the lesion after puberty, the size of the cartilaginous cap can be well established with T2-weighted magnetic resonance (MR) imaging [64].
A cartilage cap >1.5 cm should be regarded with caution.
The role of 18 Fluoro-deoxyglucose positron emission tomography (18FDG PET) needs to be further established [65].

Differential diagnosis
Dysplasia Epiphysealis Hemimelica (DEH, Trevor's disease, tarso-epiphysial aclasis) and metachondromatosis (MC) are considered in the differential diagnosis of solitary and hereditary osteochondromas.
Despite their similarities, they were shown to be separate entities [66] and the EXT downstream pathway is not involved [67].
DEH is a developmental disorder with cartilaginous overgrowth of a portion of one or more epiphyses [68].
It predominantly affects the lower extremity on one side of the body. It is usually restricted to either the medial (most frequent) or lateral side of the limb (hemimelic).
Similar to osteochondroma, DEH is usually diagnosed prior to the age of 15 years, more often in boys than in girls, and growth of these lesions end at puberty as the growth plates close [68,69].

In contrast to MO, malignant transformation has not been reported so far [68] and there does not appear to be any genetic transmission [69-71].
MC is a rare disorder exhibiting, synchronous, both multiple osteochondromas and enchondromas in children. It has an autosomal dominant mode of inheritance [72-74] but the disorder has not been mapped in the human genome so far.
MC related osteochondromas characteristically occur in the hands and feet, predominantly the digits and toes, and point toward the adjacent growth plate, while in MO the osteochondromas are mainly located in the long or other tubular bones and point away from the epiphysis [72].

Differentiation from MO is of great clinical significance because in patients with MC the lesions do not result in shortening or deformity of affected bones as in MO, and may spontaneously decrease in size or resolve completely, both clinically and radiologically [72,74].
Moreover, MO should be distinguished from enchondromatosis (Ollier disease and Maffucci syndrome), in which multiple cartilage tumours are found in the medulla of bone, with a predilection for the short tubular bones and a unilateral predominance [75].

Upon histopathological examination of osteochondroma after surgical removal malignancy should be considered. Malignant transformation in the cartilage cap of osteochondroma leads to a secondary peripheral chondrosarcoma.
Occasionally, osteosarcomas and spindle cell sarcomas develop in the stalk of the osteochondroma [15,76-80].

Extremely rare is the occurrence of dedifferentiated peripheral chondrosarcoma, in which a low-grade chondrosarcoma that developed within an osteochondroma "dedifferentiates" into a high grade sarcoma [81,82].

Genetic counselling
MO is an autosomal dominant disorder.
Affected individuals have 50% risk of transmitting the disorder to their offspring. MO has nearly 100% penetrance.
If the exact mutation is known antenatal diagnosis is technically possible.

Management including treatment
Osteochondromas are only removed when they cause pain, when they give functional complaints for instance due to compression on nerves or vessels, or for cosmetic reasons.
Surgical treatment of forearm deformities remains controversial.
In a retrospective series 23 MO patients corrective osteotomy and/or lengthening of forearm bones was not beneficial [83].
Moreover, one should consider the possible recurrence of ulnar shortening within 1.5 years when operating skeletally immature patients [83,84].
The most beneficial procedure was excision of the osteochondromas.
The simple removal of an osteochondroma can improve forearm rotation and correct deformity [83], especially if there is an isolated tumour of the distal part of the ulna.

If the diagnosis of MO is established and all tumours are identified, patients should be well instructed to seek earlier medical attention if their condition changes, for instance if there is pain or growth of a known lesion [61].
It is important to realise that no new osteochondromas develop after puberty.
Moreover, regular follow-up to discover potential malignant transformation at an early stage to enable adequate treatment should be considered.
The risk of malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma is estimated at 1–5% [2,4,5,13,14,34].

After skeletal maturation a base-line bone scan is recommended [61].
Furthermore, baseline plain radiographs of areas that can not be manually examined, like the chest, pelvis and scapula can be performed [61].
After the base-line documentation one should consider screening patients regularly, for instance every year or every other year.
There are as yet no studies available that have proven efficacy of screening. If lesions change over time, further examination, using magnetic resonance (MR) imaging including contrast enhanced MR sequences, is indicated [61].

In case of malignancy, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed, resulting in excellent long term clinical and local results.
The most common location is however the pelvis where the large cartilage cap can be difficult to excise. In a series of 61 patients with grade I or II secondary peripheral chondrosarcoma of the pelvis published by Donati et al., a 3% local recurrence rate was found after wide resection, in contrast with 23% after inadequate excision [85].

Prognosis
Osteochondromas are benign lesions and do not affect life expectancy.
The risk of malignant transformation is 1–5%.
The prognosis for secondary peripheral chondrosarcoma is depending on histological grade: 10 year survival rates are 83% for grade I chondrosarcomas compared to 29% for grade III chondrosarcomas [86].

Unresolved questions
• How can the enormous difference in disease severity within and between families be explained?
• What drives malignant transformation of osteochondroma and can this be prevented?
• What is the role of EXT in normal cartilage growth and differentiation and in osteochondroma formation?

Acknowledgements
The author would like to thank Prof. Dr. A.H.M. Taminiau, Department of Orthopaedic Surgery, Leiden University Medical Center and Dr. S.J. Ham, Department of Orthopaedic Surgery, Onze Lieve Vrouwe Gasthuis Amsterdam for providing figures 1 and 2.

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Matsuno T, Ichioka Y, Yagi T, Ishii S: Spindle-cell sarcoma in patients who have osteochondromatosis. A report of two cases.
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Enfermedades Raras, mucho por descubrir

http://www.hoymujer.com/salud/mimos/Enfermedades,raras,mucho,descubrir,73329,02,2009.html
Enfermedades raras, mucho por descubrir
Sonia Garde
Autor: MANOLO HIDALGO
Más de tres millones de españoles la sufren.
Te enseñamos cómo reconocerlas y dónde tratarlas.
Albinismo, hidrocefalia, leucodistrofia, mastocitosis... son algunos ejemplos de las cerca de 7.000 enfermedades registradas por la Organización Mundial de la Salud (OMS) como “raras” y que afectan a 25 millones de europeos.

Su incidencia es muy baja: menos de 5 casos por 10.000 habitantes, lo que dificulta las investigaciones sobre posibles tratamientos.
Estas enfermedades pueden manifestarse a cualquier edad, aunque el 75% se desarrolla en la infancia.
Y a pesar de que la mayoría son crónicas, degenerativas, muy discapacitantes y sin curación, los afectados no reciben la suficiente ayuda.

Para paliar esta situación, la Federación Española de Enfermedades ha solicitado un pacto de Estado para garantizar la integración social, sanitaria, educativa y laboral de los más de 3 millones de españoles que las sufren.

Más inf.: 902 181 725 y en www.enfermedades-raras.org

Osteocondroma in the Lumbar Intraspinal Canal

http://www.orthosupersite.com/view.asp?rID=36011
Spine

Osteochondroma in the Lumbar Intraspinal Canal Causing Nerve Root Compression.
By Jung Xu, MS; Chao-rui Xu, MS; Hong Wu, MD; Hai-le Pan, MD; Jun Tian, MDORTHOPEDICS 2009; 32:133
February 2009

Abstract
Osteochondromas, which are benign bone tumors that usually develop on long bones, tubular bones, are rarely found in the spine. If they are located in the spinal canal, they may cause nerve root or spinal cord compression, which is a rare but potentially catastrophic manifestation of osteochondromas. In this article, we report a case of a 38-year-old man who presented with low back pain, paresthesia, and weakness of the right lower extremity aggravating gradually for 5 months.

No family history of this disease can be traced. The L4-L5 level computed tomography scan showed an abnormal bony protrusion arising from the right interior wall of L5 right lamina toward the intraspinal canal.
The protrusion compressed the L5 nerve root severely. T2-weighted magnetic resonance imaging (MRI) of the same level revealed that the L5 nerve root and spinal dura mater were notably compressed by the intraspinal extradural exostosis attached to the right lamina of L5.

Considering differential diagnosis, lumbar facet synovial cysts must be excluded as they can also cause myeloradiculopathy with the similar mechanism.
The tumor, approximately 6×7×11 mm, was identified after laminectomy of the L5 laminae. Postoperative histopathologic examination confirmed our hypothesis of benign osteochondroma. Postoperatively, the patient recovered rapidly in neurological function and was free of symptoms.
Surgery is essential to this rare case.
Computed tomography and MRI are helpful for the preoperatively precise indication of tumor extent and its relationships with the adjacent.

Osteochondromas, which are benign bone tumors that usually develop on long bones, tubular bones, are rarely found in the spine, with an incidence of only 2% to 7% of all osteochondromas.
1 The tumors have extradural and extraspinal growth patterns and neurological complications are rare.
2,3 Moreover, osteochondromas within spinal canal have a predilection for the cervical or upper thoracic regions.
4,5 To our knowledge, an osteochondroma in the lumbar intraspinal canal with nerve root compression has not yet been reported in China.
This article describes a compressive case to the right lumbar 5 (L5) nerve root secondary to an osteochondroma arising from the L4-5 intraspinal canal concomitant with nerve lesion.
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Case Report
A 38-year-old man with lumbago, weakness, and paresthesia in right lower limb presented with difficulty in walking unaided and in rising from the squatting position.
Physical examination revealed body temperature, pulse rate, respiration and blood pressure were normal and no palpable deformity on the lumbar surface.
Movement of the spinal column was limited.
Neurological examination of the right femoral rear and surae lateral revealed hypoesthesia, a positive right straight leg raising-test at 30° and grade IV paraparesis in the right lower limb. Bilateral Babinskin’ sign (+). He had no familial inherited disease.

Computed tomography (CT) scan at the L4-5 level showed an abnormal bony protrusion arising from the right lamina of L5 toward the intraspinal canal with a superficial hypodense 'cap'.
The protrusion compressed the L5 nerve root severely (Figure 1).
T2-weighted magnetic resonance imaging (MRI) of the same level revealed that the L5 nerve root and spinal dura mater were notably compressed by the intraspinal extradural exostosis attached to the right lamina of L5 (Figure 2).

Figure 1: CT scan showed a tumor of the right intraspinal canal at L5 with narrowing and causing nerve root compression.
Figure 2: T2-weighted MRI of the spine revealed an intraspinal extradural lesion from the right lamina of L5 level compressed nerve root and spinal dura mater.
Figure 3: The complete tumor was excised approximately 6×7×11 mm. Figure 4: Histopathologic examination confirmed the diagnosis of benign osteochondroma (Hematoxylin-eosin stain, original magnification ×40).

The tumor was identified after laminectomy of the L5 laminae.
The tumor was detected in an area at the intraspinal extradural and right lamina of L5, approximately 6×7×11 mm (Figure 3), and the surface covered by a bluish-white, smooth, undulating cartilage ‘cap’, with an attachment to the facet joint, which compressed the L5 nerve root. The tumor was completely excised.

Histopathologic examination confirmed the diagnosis of benign osteochondroma (Figure 4). Postoperatively, physical examination found a negative right straight leg raising test and grade V in the right lower limb.
The patient recovered rapidly in neurological function and was free of symptoms.
Postoperative CT confirmed complete excision of the tumor.

Discussion
Osteochondromas are among the most frequent of benign bone tumors.
They occur either as solitary lesions or as multiple osteochondromatosis.
6 However, the spine is affected by these tumors in only 2% to 7%.
1 Osteochondromas are commonly seen in the second or the third decade of life.

Spinal osteochondromas present as asymptomatic palpable masses or more unusually, with neurological deficit, because the majority of the lesions grow out of the spinal canal and usually do not cause symptoms.
7 But nerve root compression is an uncommon manifestation of exostosis developed within the intraspinal canal. Neurological compromise is more common in the patient.

The neuroimaging findings of osteochondroma reveal a characteristic well-circumscribed lobulated mass with areas of ring-like chondral mineralization as well as calcifications representing mature trabeculated bone.
Radiographs could not establish the diagnosis in this case, possibly because of overlapping of the vertebral plate as well as soft-tissue shadows.

Preoperative diagnosis was facilitated by three-dimensional reconstruction of CT.
Moreover, by giving a precise indication of tumor extent, as well as of its relationships with the adjacent structures, CT was of great value also with regard to surgical treatment. Magnetic resonance imaging was useful in a suspected case of osteochondroma arising from the spine.

8,9 Magnetic resonance imaging demonstrates the relationship of the tumor, the nerve root, and adjacent soft tissue to each other. However, diagnosis by MRI may be made difficult due to unusual gadolinium enhancement by the tumor.

10 Lumbar facet synovial cysts must be kept in mind in the differential diagnosis. These cysts have intraspinal and extradural location and originate from the facet capsules caused by degeneration of the facet joints.
They can also cause myeloradiculopathy, depending on the level of occurrence due to compression of the nerve roots. On CT scans, a thick, cystic structure in the area with the facet joint, and on MRI, capsule with contrast enhancement are characteristic for synovial cysts.

11 Magnetic resonance imaging typically appears as a sharply marginated epidural mass in which the contents most commonly appear isointense to cerebrospinal fluid on T1-weighted images and hyperintense to cerebrospinal fluid on T2-weighted images.

12 Early diagnosis and therapy would most likely reduce the chance of permanent neurologic deficit from a spinal osteochondroma. Radical excision of the apophysis is the choice of treatment and is almost curative.2,8,10,13,14 Recurrences are rare.2,8,9

References
Bell MS. Benign cartilaginous tumours of the spine: A report of one case together with a review of the literature. Br J Surg. 1971; 58(9):707-711.
Sharma MC, Arora R, Deol PS, Mahapatra AK, Sarkar C. Osteochondroma of the spine: an enigmatic tumor of the spinal cord. A series of 10 cases. J Neurosurg Sci. 2002; 46(2):66-70.
Fiumara E, Scarabino T, Guglielmi G, Bisceglia M, D’Angelo V. Osteochondroma of the L-5 vertebra: a rare cause of sciatic pain. Case report. J Neurosurg. 1999; 91(2 Suppl):219-222.
Kouwenhoven JW, Wuisman PI, Ploegmakers JF. Headache due to an osteochondroma of the axis. Eur Spine J. 2004;13(8):746-749.
Byung-June J, Seung-Eun C, Sang-Ho L, Hyeop JS, Suk PS. Solitary lumbar osteochondroma causing sciatic pain. Joint Bone Spine. 2007; 74(4):400-401.
Tang WM, Luk KD, Leong JC. Costal osteochondroma. A rare cause of spinal cord compression. Spine. 1998; 23(17):1900-1903.
Ohtori S, Yamagata M, Hanaoka E, et al. Osteochondroma in the lumbar spinal canal causing sciatic pain: report of two cases. J Orthop Sci. 2003; 8(1):112-115.
Song KJ, Lee KB. Solitary osteochondroma of the thoracic spine causing myelopathy. Eur J Pediatr Surg. 2007; 17(3):210-213.
Faik A, Mahfoud Filali S, Lazrak N, El Hassani S, Hajjaj-Hassouni N. Spinal cord compression due to vertebral osteochondroma: report of two cases. Joint Bone Spine. 2005; 72(2):177-179.
Morikawa M, Numaguchi Y, Soliman JA. Osteochondroma of the cervical spine. MR findings. Clin Imaging. 1995; 19(4):275-278.
Karaeminogullari O, Sahin O, Demirörs H, Tandogan R. Symptomatic lumbar intraspinal synovial cyst: a case report [in Turkish]. Acta Orthop Traumatol Turc. 2006; 40(1):85-88.
Marichal DA, Bertozzi JC, Rechtine G, Murtagh FR. Case 101: lumbar facet synovial cyst. Radiology. 2006; 241:618-621.
Zhao CQ, Jiang SD, Jiang LS, Dai LY. Horner Syndrome due to a solitary osteochondroma of C7: a case report and review of the literature. Spine. 2007; 32(16):E471-E474.
Akagi S, Hashiguchi J, Sasai K, Kato I, Saito T, Ogawa R. Osteochondroma of the upper cervical spine presenting as vertigo. Orthopedics. 2003; 26(2):187-188.
Authors
Mr Xu (Jun) and Drs Pan and Tian are from the Department of Orthopedics, the Second Affiliated Hospital, Harbin Medical University, Mr Xu (Chao-rui) is from the Department of Geriatrics, Heilongjiang Provincial Hospital, and Dr Wu is from the Department of Pharmacology, Mudanjiang Medical College, China.
Messrs Xu (Jun) and Xu (Chao-rui) and Drs Wu, Pan, and Tian have no relevant financial relationships to disclose.
Correspondence should be addressed to: Jun Tian, MD, the Second Affiliated Hospital, Haerbin Medical University, 246 Xuefu Rd, Nangang District, Harbin, Heilongjiang 150081, P. R. of China.

Hallado un gen que hace "inmortales" los cánceres

http://www.elperiodico.com/default.asp?idpublicacio_PK=46&idioma=CAS&idnoticia_PK=584734&idseccio_PK=1021&h=090206
6/2/2009 SALUD
Hallado un gen que hace 'inmortales' los cánceres
EL PERIÓDICO BARCELONA.

La entrada en acción de un gen llamado CIRP es uno de los factores que propician que una célula humana suspenda su ciclo vital natural --es decir, nacer, ejercer una función y morir, lo que se denomina apoptosis-- y pase a ser inmortal, reproduciéndose indefinidamente y causando un cáncer.

La revista científica Molecular and Cellular Biology ha recogido este hallazgo, realizado en el Institut de Recerca del Hospital del Vall d'Hebron de Barcelona.
El descubrimiento, indicaron los investigadores, tal vez permitirá desarrollar un mecanismo que desactive esa condición de inmortalidad y convierta en temporales y transitorias las células de los tumores malignos, que en la actualidad invaden el cuerpo hasta acabar con él.

Los tratamientos químicos suprimen todo el tejido celular --el sano y el enfermo-- pero no revierten su inmortalidad.
El grupo del Vall d'Hebron ha seguido las pautas de las células madre para alcanzar al mencionado gen CIRP.

vidas marcadas por el dolor

http://www.20minutos.es/noticia/445991/0/enfermedades/raras/espana/
Vidas marcadas por el dolor
M. R. PRIEGO. 27.01.2009 - 04:39h

La ‘chica burbuja' o los ‘niños mariposa' son algunos ejemplos de las llamadas enfermedades raras.
En España 3 millones de personas sufren alguna de estas dolencias.
Hay registradas entre 5.000 y 7.000.

Esperas tu bebé con la mayor ilusión del mundo.
Durante el embarazo todo parece normal, las pruebas no reflejan nada extraño y tu hijo nace, aparentemente, sin problemas. Pero al tiempo, empiezas a notar que algo falla en tu bebé y comienza el baile de pruebas y hospitales.

Nadie sabe darte un diagnóstico y sigue la incertidumbre hasta que un día te dicen que tu hijo sufre una enfermedad de la que no has oído hablar. Además, no es precisamente sencillo acceder a un tratamiento.
Te hundes y no sabes qué hacer, pero continúas luchando.
Se dan menos de 5 casos por cada 10.000 habitantes.
Éste es un ejemplo de lo que pueden vivir unos padres cuyo hijo padezca una enfermedad rara, que se caracterizan por ser poco frecuentes (menos de 5 casos por cada 10.000 habitantes).
3 millones de españoles sufren dolencias de este tipo, y en todo el mundo, entre el 6% y el 8% de la población.

Pero hay casi tantas historias como enfermedades (se han registrado entre 5.000 y 7.000 dolencias raras), ya que en otras patologías los síntomas son más claros, como en los afectados por epidermolisis bullosa, los niños mariposa, que nacen con la piel tan frágil como las alas de los insectos, por lo que sufren heridas con cada contacto.
También tienen ampollas y hasta un abrazo puede dañarles.

Lo importante, no rendirse.
Sofía tiene 6 años y padece el síndrome 5p menos, conocido como Maullido de Gato, llamado así por el llanto de los afectados, ya que, debido a un estrechamiento de la laringe, éste suena como el maullido de estos animales.

Nadie te prepara para un diagnóstico tan fatal".
"Se lo detectaron a los dos meses de nacer", explica su madre, Sonia Saiz, a 20 Minutos. "Deseaba ser madre desde hacía mucho tiempo. Nadie te prepara para un diagnóstico tan fatal", cuenta esta madre, quien reconoce que cuando se lo dijeron los médicos quiso "salir corriendo".
A Sonia, vicepresidenta de la Fundación Síndrome 5p menos, le dijeron que lo máximo a lo que llegaría Sofía sería a vestirse sola de adulta, pero ella y su marido decidieron luchar.
Afirma que no recibieron mucha ayuda y que la información que hallaron era bastante negativa. Lo importante, dice, es "no rendirse".

SÍNDROME DEL MAULLIDO DEL GATO .
También llamado síndrome 5p menos por la pérdida de material genético del brazo corto del cromosoma 5. Sólo cuatro características son comunes en casi todos los afectados: llanto similar al maullido de los gatos, microcefalia, crecimiento lento y deficiencia mental.
Sonia. 38 años.
"No ve malicia en la gente"
"Sofía tiene seis años, es muy cariñosa y no ve la malicia en la gente", afirma su madre, Sonia, que desde la Fundación Síndrome 5p menos lucha por lograr que se hagan más estudios para que se beneficien todos los niños afectados.

SÍNDROME DE RETT
Es un trastorno neurológico de base genética que afecta a las niñas.
El desarrollo es normal, pero entre los 6 y los 18 meses de edad comienzan a tener problemas. La niña pierde el uso de las capacidades manuales y el desarrollo intelectual se retrasa de forma severa.
Josele. 39 años.
"Para los padres es duro"
Josele sale a correr con María (nueve años), aunque ella esté en silla de ruedas, porque a su hija le encanta. "Un club deportivo me regaló un carro especial", dice Josele.
"Para los padres es muy duro, preferirías que te pasara a ti", añade.

OTRAS PATOLOGÍAS POCO HABITUALES
Sensibilidad química múltiple. Los afectados no pueden tener contacto con productos químicos. Es el caso de la valenciana Elvira Roda , conocida también como ´la chica burbuja´.
Síndrome de Joubert. Es una dolencia neurológica por la que el cerebelo no se desarrolla correctamente.
Tricotiodistrofia. Nadia, una niña mallorquina de 3 años que la sufre, nació con una capa cubriendo su piel parecida a la de un reptil debido a la escasez de azufre en el pelo.

PRIMER REGISTRO NACIONAL
Desde la Federación Española de Enfermedades Raras (Feder) son conscientes de que hay una mayor concienciación para apoyar a los afectados y sus familias, pero apuntan que los esfuerzos deberían reconducirse hacia políticas y planes que les faciliten la vida y creen importante que se ayude en el acceso a los tratamientos.
Pero los avances se dan, como la reciente puesta en marcha del primer registro nacional de enfermedades raras (creado por el Instituto de Salud Carlos III y en el que colabora Feder), cuyo objetivo es favorecer la investigación de estas patologías, además de ser una herramienta de información para investigadores, médicos y afectados.

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El centro de enfermedades raras dedicará un tercio de instalaciones a la investigación
Las enfermedades genéticas raras afectan a entre el 3% y el 4% de los recién nacidos
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