Natural History, Pathogenesis and Outcome of Melorheostosis A Rare Osteosclerotic Disease

Overview

Background: \- The rare disease melorheostosis causes bones to thicken. This may lead to pain, and can affect bones, joints, and muscles. Researchers want to learn more about the disease and how it progresses. Objective: -To see what happens to people with melorheostosis over time and understand the causes of the disease. Eligibility: * People 18 and over with melorheostosis. * Their unaffected relatives. Design: * All participants will have a medical history and physical exam. * Participants who are relatives will give samples of blood or cheek cells. * Other participants will be in the study for about 1 week. * They will have blood and urine collected. * Strength, walking, and range of motion will be measured. * Participants may also have * X-rays and scans. * A pain and neurological evaluation. * Their skin evaluated by a dermatologist. * A small sample of bone taken. * Nerve conduction studies. Small electrodes with to wires will be put on the skin. A metal probe will give a small electrical shock. * Electromyography. A thin needle will be placed into the muscles. * An ultrasound, which uses sound waves to examine the muscles and nerves. An ultrasound probe will be placed over the skin. * A bone scan. They will get a small amount of radioactive fluid through a needle in an arm vein. This fluid travels to the bones. The bones will be photographed in a machine. * Bone Densitometry, a low-level x-ray. * Photographs taken. * A small circle of skin removed with a surgical instrument. * Questionnaires about their quality of life. * Participants will be asked to return about every 2 years. At these visits, participants may have blood and urine tests and x-rays.

Melorheostosis is a rare osteosclerotic disease resulting in exuberant excessive bone growth with a characteristic radiographic appearance often described as dripping candle wax. As a result of these bony formations, patients report mild-moderate pain that interferes with their routine activities. It is usually diagnosed on radiographs but bone biopsy may be performed to exclude other osteosclerotic diseases and/or osteosarcoma. Deformities, limb-length discrepancy, muscle atrophy, neurological deficit have been reported as complications. A subset of patients have somatic mutations in MAP2K1. The cause of this disease is not known in all patients, the natural history poorly described and there is no clearly-defined systemic therapy. We propose a prospective observational study to investigate the natural history and pathogenesis of the disease. Subjects will undergo standardized initial evaluation and medically indicated testing. Skin biopsies may be performed to test for known mutations related to melorheotosis, and if negative affected bone and/or skin may be sent for genetic testing for acquired somatic mutations in genes that control bone homeostasis. Enrolled subjects will be followed every two to three years for assessment of disease progression and receive testing and treatment. The study of this rare bone disease offers the potential to generate new insights, provide answers as well as generate new questions into the biology of the skeletal and mineral metabolism.