NORD gratefully acknowledges Kristina Bundra, Pharm. D, NORD Editorial Intern, and Geert Mortier, MD, PhD, Chairman, Department of Medical Genetics, Antwerp University Hospital, Professor of Medical Genetics, University of Antwerp, Belgium, for assistance in the preparation of this report.
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; soft tissue abnormalities, including tendon and ligament shortening, absent or abnormal muscles, subcutaneous calcification, joint swelling 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 very small number of melorheostosis patients, who belong to a family where osteopoikilosis or Buschke-Ollendorff syndrome does occur, a mutation in the LEMD3 gene has been identified. Mutations in the LEMD3 gene have been predominantly found in patients with osteopoikilosis or the Buschke-Ollendorff syndrome.
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.
The estimated incidence of melorheostosis is 1 in 1,000,000. Both sexes are affected and approximately 400 cases have been reported.
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.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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 Rep. 2013 Jun 21;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. Last Update 04/15/2015. Available at http://omim.org/entry/155950 Accessed January 9, 2017.
Azouz EM, Greenspan A. Melorhesostosis. Orphanet Encyclopedia. February 2005. Available at https://www.orpha.net/data/patho/GB/uk-Melorheostosis.pdf Accessed January 9, 2017.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100