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It is possible that the main title of the report Melorheostosis is not the name you expected.
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Melorheostosis is a rare and progressive disease characterized by thickening or widening (hyperostosis) of the outer layers of the bone (cortical bone). Melorheostosis affects both bone and soft tissue growth and development. This disorder is benign (noncancerous), but it often results in severe functional limitation; chronic pain; malformed or immobilized muscles, tendons or ligaments; and limb, hand, or foot deformities.
Signs and symptoms of melorheostosis include irregular bone growth, including cortical thickening and "dripping candle wax" appearance on x-ray imaging; unequal length of limbs; joint swelling and fusion; soft tissue abnormalities, including tendon and ligament shortening, absent or abnormal muscles, subcutaneous calcification, and contractures resulting in malformed or immobilized joints; range of motion limitations; pain and stiffness; limb swelling (edema) and vascular abnormalities. Less commonly, but severe, the bone lesions may compress the surrounding nerves.
Melorheostosis usually affects one particular segment of the appendicular skeleton (arms and legs). It is usually limited to one side of the body (rarely bilateral) and within a limb restricted to either the medial or lateral side of the bones. The disease can also affect the axial skeleton: pelvis, sternum, ribs and, more rarely, the spine and skull. Symptoms may progressively worsen over time.
In children, the condition usually presents with limb length inequality, deformity, or joint contractures. In adults, symptoms of pain, joint stiffness, and progressive deformity are more apparent.
The age of diagnosis is typically based on severity of onset and symptoms and varies widely in children and adults. Melorheostosis is usually observed in early childhood and may even be apparent in the first days of life. Fifty percent of patients with melorheostosis will develop symptoms by age 20.
Up to now the precise cause of melorheostosis is still unknown. In a small number of melorheostosis patients, a mutation in the LEMD3 gene has been identified. The LEMD3 gene codes for a protein that is part of the nuclear membrane. This membrane protein plays an inhibitory role in bone formation. However, the vast majority of sporadic patients with melorheostosis do not have a LEMD3 germline (egg or sperm) mutation. The current hypothesis is that melorheostosis is caused by a somatic mutation that is only present in the affected tissues. Mutations in the LEMD3 gene have also been associated with other bone disorders (osteopoikilosis or Buschke-Ollendorff syndrome).
The estimated incidence of melorheostosis is 1 in 1,000,000. Both sexes are affected and approximately 400 cases have been reported.
Symptoms of the following disorders can be similar to those of melorheostosis. Comparison may be useful for a differential diagnosis:
Osteopoikilosis is a rare and benign bone disorder characterized by multiple round or oval areas of increased bone density.
Osteopathia striata is a benign bone disorder characterized by longitudinal "stripes" of increased density in affected bones.
Buschke-Ollendorf syndrome is a rare hereditary disorder of connective tissue characterized by skin growths called connective tissue nevi and osteopoikilosis.
Linear scleroderma appears as a band-like thickening of skin on the arms and legs. It typically appears first during early childhood and is characterized by the failure of one limb to grow as rapidly as its counterpart.
Desmoid tumors commonly develop in the fibrous (connective) tissue of the body that forms tendons and ligaments, usually in the arms, legs or midsection, and also in the head and neck. Desmoid tumors can be invasive to surrounding tissues and difficult to control. (For more information on this disorder, choose "desmoid tumor" as your search term in the Rare Disease Database.)
Hemangiomas appear in early infancy and are growths made up of small blood vessels.
Scoliosis refers to side-to-side curvature of the spine. In the person with scoliosis, the spine may resemble an "S" rather than a straight line.
In melorheostosis, bone scans appear to be markedly positive. However, on magnetic resonance imaging (MRI) there is usually a low signal. X-ray imaging is the preferred diagnostic tool for melorheostosis. X-rays often reveal a pattern of thickened bone (sclerotic bone lesions) that resembles dripping candle wax.
Treatments are limited at the present time and are predominantly aimed at reducing symptoms. No treatment option has been found to be fully effective, and what may be helpful to one person may be ineffective or even detrimental to another. Treatment options may include surgery, physical and occupational therapy, hydrotherapy, and medications to alter the bone remodeling process.
Pain management may be challenging. Medications prescribed for pain may include non-steroidal anti-inflammatory drugs (NSAIDs),steroids or rarely narcotics. These medications are sometimes helpful in the early stages of the chronic progression of the disease but may be less so for the severely affected. However, some patients have shown benefit in either symptoms or on bone scans.
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Kasper, DL, Fauci AS, Longo DL, et al., eds. Harrison's Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:2283.
James WD, Berger T, Elston DM, eds. Andrew's Diseases of the Skin: Clinical Dermatology. 10th ed. Saunders Elsevier. Philadelphia, PA. 2006:171.
Beighton P, ed. Mckusick's Heritable Disorders of Connective Tissue. 5th ed. St. Louis, MO: Mosby-Year Book, Inc; 1993:657
Slimani S, Nezzar A, Makhloufi H. Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy. BMJ Case Reports. 2013.
Motimaya AM, Meyers SP. Melorheostosis Involving the Cervical and Upper Thoracic Spine: Radiographic, CT, and MR Imaging Findings. AJNR Am J Neuroradiol. 2006;27:1198-1200.
Zeiler SC, Vaccaro AR, Wimberley DW, Albert TJ, Harrop JS, Hilibrand AS. Severe myelopathy resulting from melorheostosis of the cervicothoracic spine. A case report. J Bone Joint Surg Am. 2005;87:2759-62.
Wollridge B, Stone NC, Denic N. Melorheostosis isolated to the calcaneus: a case report and review of the literature. Foot Ankle Int. 2005;26:660-63.
Reznik M, Fried GW. Myelopathy associated with melorheostosis: a case report. Arch Phys Med Rehabil. 2005;86:1495-97.
Schreck MA. Melorheostosis in a pediatric patient. J Am Podiatr Med Assoc. 2005;95:167-70.
Ethunandan M, Khosla N, Tilley E, Webb A. Melorheostosis involving the craniofacial skeleton. J Craniofac Surg. 2004;11:1062-65.
Shivanand G. Srivastava DN. Melorheostosis with scleroderma. Clin Imaging. 2004;28:214-15.
Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. 2004;36:1213-18.
Happle R. Melorheostosis may originate as a type 2 segmental manifestation of osteopoikilosis. Am J Med Genet A. 2004;15:221-23.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Melorheostosis. Entry Number;155950. Available at http://omim.org/entry/155950 Last Edit Date; 04/04/2013. Accessed March 10, 2014.
Azouz EM, Greenspan A. Melorhesostosis. Orphanet Encyclopedia. February 2005. Available at https://www.orpha.net/data/patho/GB/uk-Melorheostosis.pdf Accessed March 10, 2014.
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Last Updated: 3/20/2014
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