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.
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