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Acta Reumatologica Portuguesa 2020
Topics: Humans; Male; Melorheostosis; Middle Aged; Trigger Finger Disorder
PubMed: 32578577
DOI: No ID Found -
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 -
The Journal of Experimental Medicine May 2020In the current issue of JEM, Kang et al. (https://doi.org/10.1084/jem.20191499) describe somatic mutations in the SMAD3 gene causing endosteal melorheostosis. Using...
In the current issue of JEM, Kang et al. (https://doi.org/10.1084/jem.20191499) describe somatic mutations in the SMAD3 gene causing endosteal melorheostosis. Using osteoblast models, the identified mutations are demonstrated to exert a gain-of-function mechanism, augmenting transforming growth factor (TGF) β signaling. These findings provide further insights into the genetic etiology of melorheostosis and consolidate the importance of the TGFβ pathway in skeletal disorders.
Topics: Humans; Melorheostosis; Mutation; Osteoblasts; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta
PubMed: 32289153
DOI: 10.1084/jem.20200185 -
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 -
Journal of Clinical Orthopaedics and... 2020Melorheostosis is a rare chronic bone disease, etiology of which remains unclear. It mostly affects lower limbs and clinical features vary in each case. Radiographs show...
Melorheostosis is a rare chronic bone disease, etiology of which remains unclear. It mostly affects lower limbs and clinical features vary in each case. Radiographs show characteristic "candle wax pattern" of hyperostosis. Herein we report four cases of upper limb affection with their symptoms, radiographic findings and treatment. First case presented with gradually progressive swelling in forearm which was initially misdiagnosed as filariasis. Plain radiograph eventually demonstrated melorheostosis of ulna. Second patient had deformity of index finger and pain in hand which was diagnosed on radiograph of hand. Third case presented with progressive flexion deformity of ring and little finger. Fourth patient had ulnar involvement which was an incidental diagnosis. First three patients were managed with bisphosphonates following which there was significant improvement in pain and fourth case was kept on follow-up as he was asymptomatic.
PubMed: 32099304
DOI: 10.1016/j.jcot.2019.06.009 -
Bone Jan 2020Recent clinical studies have revealed that a somatic mutation in MAP2K1, causing constitutive activation of MEK1 in osteogenic cells, occurs in melorheostotic bone...
Recent clinical studies have revealed that a somatic mutation in MAP2K1, causing constitutive activation of MEK1 in osteogenic cells, occurs in melorheostotic bone disease in humans. We have generated a mouse model which expresses an activated form of MEK1 (MEK1DD) specifically in osteoprogenitors postnatally. The skeletal phenotype of these mice recapitulates many features of melorheostosis observed in humans, including extra-cortical bone formation, abundant osteoid formation, decreased mineral density, and increased porosity. Paradoxically, in both humans and mice, MEK1 activation in osteoprogenitors results in bone that is not structurally compromised, but is hardened and stronger, which would not be predicted based on tissue and matrix properties. Thus, a specific activating mutation in MEK1, expressed only by osteoprogenitors postnatally, can have a significant impact on bone strength through complex alterations in whole bone geometry, bone micro-structure, and bone matrix.
Topics: Animals; Bone and Bones; Melorheostosis; Mice; Mutation; Osteogenesis; Phenotype
PubMed: 31689526
DOI: 10.1016/j.bone.2019.115106 -
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 -
JBMR Plus Aug 2019Melorheostosis is a rare dysostosis involving cortical bone overgrowth that affects the appendicular skeleton. Patients present with pain, deformities, contractures,...
Melorheostosis is a rare dysostosis involving cortical bone overgrowth that affects the appendicular skeleton. Patients present with pain, deformities, contractures, range of motion limitation(s), and limb swelling. It has been described in children as well as adults. We recently identified somatic mosaicism for gain-of-function mutations in in patients with melorheostosis. Despite these advances in genetic understanding, there are no effective therapies or clinical guidelines to help clinicians and patients in disease management. In a study to better characterize the clinical and genetic aspects of the disease, we recruited 30 adults with a radiographic appearance of melorheostosis and corresponding increased uptake on F-NaF positron emission tomography (PET)/CT. Patients underwent physical exam, imaging studies, and laboratory assessment. All patients underwent nerve conduction studies and ultrasound imaging of the nerve in the anatomic distribution of melorheostosis. We found sensory deficits in approximately 77% of patients, with evidence of focal nerve entrapment in five patients. All patients reported pain; 53% of patients had changes in skin overlying the affected bone. No significant laboratory abnormalities were noted. Our findings suggest that patients with melorheostosis may benefit from a multidisciplinary team of dermatologists, neurologists, orthopedic surgeons, pain and palliative care specialists, and physical medicine and rehabilitation specialists. Future studies focused on disease management are needed. © 2019 The Authors. Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
PubMed: 31485554
DOI: 10.1002/jbm4.10214 -
The American Journal of Surgical... Nov 2019Melorheostosis is a rare sclerosing bone disease characterized by excessive cortical bone deposition that is frequently on the differential diagnosis for bone biopsies.... (Clinical Trial)
Clinical Trial
Melorheostosis is a rare sclerosing bone disease characterized by excessive cortical bone deposition that is frequently on the differential diagnosis for bone biopsies. Although the radiologic pattern of "dripping candle wax" is well known, the pathologic findings have been poorly defined. Here, we comprehensively describe the histology of melorheostosis in 15 patients who underwent bone biopsies. Common histologic findings included: dense cortical bone (73.3%), woven bone (60%), and hypervascular features and increased porosity (66.7%). One third of the patients (5/15) also had prominent cement lines. Multiple patients had >1 histologic pattern (ie, dense cortical bone and hypervascularity). Overall, this study suggests that melorheostosis exists with several histologically distinct patterns. When confronted with a case of suspected melorheostosis, the clinical pathologist should use the histologic features common to melorheostotic lesions presented here in conjunction with the patient's clinical presentation and radiographic findings to arrive at a diagnosis. An illustrative case is presented.
Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Male; Melorheostosis; Middle Aged; Radiography
PubMed: 31386640
DOI: 10.1097/PAS.0000000000001310 -
Clinical Case Reports May 2019It is important to consider the rare case of a melorheostosis in patients presenting with soft tissue swelling, joint contractures, and "dripping candle wax"-like...
It is important to consider the rare case of a melorheostosis in patients presenting with soft tissue swelling, joint contractures, and "dripping candle wax"-like hyperostoses visible on hand radiographs. Clinical sequelae such as carpal tunnel syndrome or trigger finger have to be ruled out. Symptomatic therapy is usually sufficient.
PubMed: 31110758
DOI: 10.1002/ccr3.2160