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.
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.
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.
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