We're celebrating
40 years!
Last updated:
March 25, 2021
Years published: 2006, 2014, 2017, 2021
NORD gratefully acknowledges Kristina Bundra, Pharm. D, NORD Editorial Intern, and Geert Mortier, MD, PhD, Chairman, Department of Medical Genetics, Antwerp University Hospital, and Professor of Medical Genetics, University of Antwerp, Belgium, for assistance in the preparation of this report.
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; joint contractures and/or stiff 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; 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.
Melorheostosis is usually an isolated disorder. However, it has also been observed in a few families with osteopoikilosis or the Buschke- Ollendorff syndrome due to a change (mutation) in the LEMD3 gene. The sporadic occurrence of the disorder with no reports of parent to child transmission and the localized distribution of bone lesions led to the hypothesis that a somatic mutation may be responsible for the disease. This hypothesis was recently proven by the identification of somatic mutations in the MAP2K1 gene and the SMAD3 gene. There is also indication that somatic mutations in other, yet unknown, genes may be responsible for the disorder. Somatic mutations are changes in DNA that occur after conception, so they are not present in egg or sperm cells and are not passed down in families.
The estimated incidence of melorheostosis is 1 in 1,000,000. Males and females 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.
Treatment
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: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
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.
JOURNAL ARTICLES
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.
INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Melorheostosis. Entry Number;155950. Last Update 06/22/2020. Available at: http://omim.org/entry/155950 Accessed March 25, 2021.
Azouz EM, Greenspan A. Melorhesostosis. Orphanet Encyclopedia. February 2005. Available at: https://www.orpha.net/data/patho/GB/uk-Melorheostosis.pdf Accessed March 25, 2021.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/
