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Proceedings of the Royal Society of... Apr 1950
Topics: Humans; Melorheostosis
PubMed: 15417575
DOI: No ID Found -
The Indian Journal of Radiology &... Sep 2022Axial melorheostosis is rare with only few cases reported and even fewer with symptoms. While symptoms secondary to neural foramen or spinal canal stenosis caused by...
Spinal Melorheostosis Associated with Intradural Fibrous Band and Extensive Lipomatosis Causing Thoracic Cord Tethering and Myelomalacia: A Unique Case Highlighting Importance of MRI in Management.
Axial melorheostosis is rare with only few cases reported and even fewer with symptoms. While symptoms secondary to neural foramen or spinal canal stenosis caused by hyperostotic bone are common, only three symptomatic cases of spinal melorheostosis with associated intradural lipomatous lesions have been reported to date. In none of them the fibrous component of lipofibromatous lesion was identified preoperatively on magnetic resonance imaging. We report here a case of 18-year-old male who presented with thoracic myelopathy secondary to widespread spinal melorheostosis associated with extensive intradural lipomatosis and fibrous component in thoracic lipoma, causing tethering of thoracic spinal cord and myelomalacia. The patient was treated with T2 to T9 posterior instrumented stabilization followed by T3 to T8 laminectomy along with selective thoracic lipofibromatous tumor debulking. Detection of the fibromatous component in multilevel extensive intradural lipomatosis associated with melorheostosis is helpful in planning selection of the level of surgical excision and decompression.
PubMed: 36177288
DOI: 10.1055/s-0042-1748883 -
Nature Communications Apr 2018Melorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we...
Melorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we identify somatic mosaic MAP2K1 mutations in affected, but not unaffected, bone of eight unrelated patients with melorheostosis. The activating mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2 activation, and increased cell proliferation. However, these MAP2K1 mutations inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro, underlying the markedly increased osteoid detected in affected bone histology. Mosaicism is also detected in the skin overlying bone lesions in four of five patients tested. Our data show that the MAP2K1 oncogene is important in human bone formation and implicate MEK1 inhibition as a potential treatment avenue for melorheostosis.
Topics: Bone Morphogenetic Protein 2; Bone and Bones; Calcification, Physiologic; Cell Differentiation; Cell Proliferation; Gene Expression Regulation; Humans; MAP Kinase Kinase 1; Melorheostosis; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mosaicism; Mutation; Osteoblasts; Osteogenesis; Primary Cell Culture; Signal Transduction; Skin; Exome Sequencing
PubMed: 29643386
DOI: 10.1038/s41467-018-03720-z -
The Journal of Experimental Medicine May 2020Melorheostosis is a rare sclerosing dysostosis characterized by asymmetric exuberant bone formation. Recently, we reported that somatic mosaicism for MAP2K1-activating...
Melorheostosis is a rare sclerosing dysostosis characterized by asymmetric exuberant bone formation. Recently, we reported that somatic mosaicism for MAP2K1-activating mutations causes radiographical "dripping candle wax" melorheostosis. We now report somatic SMAD3 mutations in bone lesions of four unrelated patients with endosteal pattern melorheostosis. In vitro, the SMAD3 mutations stimulated the TGF-β pathway in osteoblasts, enhanced nuclear translocation and target gene expression, and inhibited proliferation. Osteoblast differentiation and mineralization were stimulated by the SMAD3 mutation, consistent with higher mineralization in affected than in unaffected bone, but differing from MAP2K1 mutation-positive melorheostosis. Conversely, osteoblast differentiation and mineralization were inhibited when osteogenesis of affected osteoblasts was driven in the presence of BMP2. Transcriptome profiling displayed that TGF-β pathway activation and ossification-related processes were significantly influenced by the SMAD3 mutation. Co-expression clustering illuminated melorheostosis pathophysiology, including alterations in ECM organization, cell growth, and interferon signaling. These data reveal antagonism of TGF-β/SMAD3 activation by BMP signaling in SMAD3 mutation-positive endosteal melorheostosis, which may guide future therapies.
Topics: Animals; Bone Morphogenetic Protein 2; Bone and Bones; Calcification, Physiologic; Cell Differentiation; Cell Line; Cell Nucleus; Cell Proliferation; Extracellular Matrix; Gain of Function Mutation; Gene Expression Regulation; Humans; MAP Kinase Kinase 1; Melorheostosis; Mice; Models, Biological; Mutation; Osteoblasts; Osteogenesis; Protein Transport; Signal Transduction; Smad3 Protein; Transcriptome; Transforming Growth Factor beta; Up-Regulation
PubMed: 32232430
DOI: 10.1084/jem.20191499 -
Molecular Genetics & Genomic Medicine Oct 2022Melorheostosis (MEL) is an exceptionally rare sclerosing bone dysplasia with asymmetrically exuberant bone formation and soft tissue lesions in a segmental distribution....
BACKGROUND
Melorheostosis (MEL) is an exceptionally rare sclerosing bone dysplasia with asymmetrically exuberant bone formation and soft tissue lesions in a segmental distribution. We aimed to summarize the clinical characteristics of Chinese MEL patients and identify their pathogenic cause.
METHODS
In total, 10 Chinese MEL patients were recruited, and clinical manifestations and radiological characteristics were recorded. Sanger sequencing of the LEMD3 gene was performed on peripheral blood samples of all patients, while the exome sequencing of matched peripheral blood, melorheostotic bone, and skin lesion samples was conducted on one patient who provided affected bone and skin tissues. Micro-computed tomography (micro-CT) was also used to scan the melorheostotic bone tissue.
RESULTS
We found the average age of the 10 MEL patients was 29.5 years (range 11-40 years), and the major symptoms were bone pain, restricted movement, and bone deformity. The lesions sites were mainly located in femur (8/10), tibia (8/10), fibula (6/10), and foot (7/10), the next was pelvis (4/10), and the last were patella (1/10), hand (1/10) and spine (1/10). Radiological examinations showed a mixture of hyperostosis consisting of classic "dripping candle wax," "osteoma-like," or "myositis ossificans-like" patterns in most patients. No germline pathogenic variants in the LEMD3 gene were found in all patients, but a disease-causing somatic variant of MAP2K1 (c.167A > C, p.Gln56Pro) was detected in melorheostotic bone from one patient. Moreover, the micro-CT analysis showed increased porosity in the melorheostotic bone with somatic MAP2K1 variant.
CONCLUSION
This is a summary of the clinical characteristics of Chinese MEL patients and we first identify the somatic MAP2K1 variant in Chinese patients. Our findings validate the molecular genetic mechanism of MEL and broaden its phenotype spectrum in the Chinese population.
Topics: Bone and Bones; China; Humans; MAP Kinase Kinase 1; Melorheostosis; Exome Sequencing; X-Ray Microtomography
PubMed: 36004822
DOI: 10.1002/mgg3.2043 -
Reumatismo Mar 2024Melorheostosis is a rare, non-hereditary, benign bone disease characterized by abnormal bone growth. Generally, melorheostosis develops during childhood or adolescence... (Review)
Review
OBJECTIVE
Melorheostosis is a rare, non-hereditary, benign bone disease characterized by abnormal bone growth. Generally, melorheostosis develops during childhood or adolescence and progresses gradually over time. This disease represents a true challenge to the physician because of its variability due to location, extension of the affected bone, and involvement of associated soft tissue. Pain management, physical therapy, and surgery may be recommended, depending on the individual case. This review aims to get an overview of the latest evidence relating to epidemiology, clinical and radiographic characteristics, diagnosis, and possible therapeutic strategies for melorheostosis and describe our experience through a clinical case.
METHODS
We designed a comprehensive literature search on melorheostosis in MEDLINE (via Pubmed) up to April 2023 and reviewed reports published in international journals.
RESULTS
The purpose is to highlight the importance of a multidisciplinary approach in the management of a rare disease such as melorheostosis. We discuss the role of different physicians, including genetists, rheumatologists, physiatrists, physical therapists, and orthopedic surgeons, in providing accurate diagnoses and effective treatments. We conducted a comprehensive review of the literature on the treatment of melorheostosis to support these findings. In addition, the article presents a case study of a patient suffering from melorheostosis, focusing on difficulties in reaching a correct diagnosis and attempts towards conservative and surgical interventions. The patient underwent hip arthroplasty, and the final result was an improvement in function and a reduction in pain.
CONCLUSIONS
Managing melorheostosis can be challenging, and there is no standardized treatment for this condition at the moment.
Topics: Adolescent; Humans; Melorheostosis; Pain; Pain Management; Treatment Outcome; Rare Diseases
PubMed: 38523583
DOI: 10.4081/reumatismo.2024.1621 -
International Journal of Spine Surgery Apr 2020Symptomatic spinal melorheostosis is a rare entity, and its surgical management is even rarer. Our objective is to highlight the importance of considering spinal...
BACKGROUND
Symptomatic spinal melorheostosis is a rare entity, and its surgical management is even rarer. Our objective is to highlight the importance of considering spinal melorheostosis among the differential diagnosis of thoracic radiculopathy.
METHODS
We report a case of melorheostosis involving the T9 vertebra presenting with unilateral radicular pain managed surgically by decompression and posterior stabilization.
RESULTS
Our patient had complete symptomatic relief following surgical resection without any perioperative complications.
CONCLUSIONS
Spinal melorheostosis, although rare, forms an important differential diagnosis in patients presenting with thoracic radiculopathy where surgical management can be a viable option in cases refractory to conservative treatment.
LEVEL OF EVIDENCE
5.
PubMed: 32355627
DOI: 10.14444/7027 -
Journal of Orthopaedic Case Reports Dec 2020Melorheostosis is a rare condition affecting the bones and has only been occasionally reported. We herein report a case of melorheostosis affecting left femur and tibia...
INTRODUCTION
Melorheostosis is a rare condition affecting the bones and has only been occasionally reported. We herein report a case of melorheostosis affecting left femur and tibia which was diagnosed based on clinical and radiological features and managed with bisphosphonates.
CASE REPORT
A 28-year-old female patient presented with complaints of pain over left knee and thigh for the past 3 months. To evaluate the cause of pain X-ray and magnetic resonance imaging were done, which revealed characteristic candle dripping wax appearance suggestive of melorheostosis. After arriving at the diagnosis patient was started on nonsteroidal anti-inflammatory drugs and pamidronate which provided symptomatic betterment patient has now been followed up for past 1 year and is symptom free.
CONCLUSION
Melorheostosis is an uncommon cause of a common symptom. Positive clinical and imaging features helped us to arrive at the diagnosis. Proper work up would help in early diagnosis and management. More evidence is needed to illustrate the effectiveness of medical or surgical treatments for patients with this rare diagnosis.
PubMed: 34169026
DOI: 10.13107/jocr.2020.v10.i09.1918 -
Journal of Orthopaedics 2019Melorheostosis, a rare mesenchymal dysplasia of bone, generally affects about 0.001% of people globally with about 400 cases total being reported. Melorheostosis of the...
Melorheostosis, a rare mesenchymal dysplasia of bone, generally affects about 0.001% of people globally with about 400 cases total being reported. Melorheostosis of the hand, especially in the pediatric population, has been seldom reported. Previous studies have investigated potential genetic mutations associated with melorheostosis however, questions still remain regarding effective treatment options for this disease. This case report describes a unique case of pediatric melorheostosis of the hand and further clarifies current theories on melorheostosis with regards to pathogenesis, best treatment practices, and future research.
PubMed: 31528051
DOI: 10.1016/j.jor.2019.06.023 -
SAGE Open Medical Case Reports 2020Melorheostosis is a rare benign bone disease including dysostosis and sclerosis. Dripping candle wax presence is a common and typical sign of melorheostosis. This sign...
Melorheostosis is a rare benign bone disease including dysostosis and sclerosis. Dripping candle wax presence is a common and typical sign of melorheostosis. This sign appears as irregular hyperostosis of the cortical bone which is likened to melted wax flowing down one side of a candle. It can sometimes cause pain, stiffness joint, or limitation of motion in the affected areas implicitly but mostly has no symptoms. It is usually observed on plain radiography; its appearance is generally hyperplasia on one side of the bone. We report a 33-year-old male who has an incidental diagnosis of melorheostosis post-trauma.
PubMed: 32922791
DOI: 10.1177/2050313X20940564