Melorheostosis
Melorheostosis is a rare, benign bone disorder characterized by abnormal, "flowing" bone growth on existing bones, leading to chronic pain and joint deformities.
Overview
Melorheostosis is a rare, noncancerous (benign) bone disease characterized by the abnormal growth of new bone tissue on the surface of existing bones. On x-rays, this new bone has a distinctive appearance often described as "flowing" or resembling dripping candle wax. The name itself is derived from the Greek words "melos" (limb), "rheos" (flow), and "ostosis" (bone formation).
The excess bone growth typically affects the bones of a single arm or leg, though it can also occur in the pelvis, breastbone (sternum), ribs, or other bones. Because the abnormal growth is benign, it does not spread from one bone to another.
While melorheostosis can sometimes occur as part of another rare disease called Buschke-Ollendorff syndrome (which features skin growths called connective tissue nevi and areas of increased bone density called osteopoikilosis), the two are separate disorders. Melorheostosis that occurs alone is caused by different gene mutations than those that cause Buschke-Ollendorff syndrome.
Symptoms
The signs and symptoms of melorheostosis usually appear during childhood or adolescence. Common features include:
- Long-lasting (chronic) pain
- Permanent joint deformities (contractures)
- A limited range of motion in the affected body part
- A thickened or enlarged appearance of the affected limb
- Red, thick, and shiny skin overlying the affected area
Frequency
Melorheostosis affects approximately 1 in 1 million people. Around 400 cases of the condition have been reported worldwide.
Causes
Mutations in the MAP2K1 gene are estimated to cause about half of all cases of melorheostosis. This gene provides instructions for making the MEK1 protein kinase, which is active in many cell types, including bone cells. This protein is a component of the RAS/MAPK signaling pathway, which helps regulate cell growth, division (proliferation), maturation (differentiation), and movement (migration). This pathway is critical for normal bone development.
The MAP2K1 gene mutations responsible for melorheostosis are somatic, meaning they are acquired during a person's lifetime and are present only in certain cells—specifically, the bone cells in the affected area of the body. These mutations cause the MEK1 protein kinase to become overactive, increasing RAS/MAPK signaling in bone tissue. This overactivity disrupts normal bone cell proliferation and stimulates excess bone remodeling (the process of breaking down old bone and creating new bone), leading to abnormal bone growth.
In cases of melorheostosis where a MAP2K1 gene mutation is not identified, the cause remains unknown. However, studies suggest that somatic mutations in other genes, particularly those related to the RAS/MAPK signaling pathway, may also be responsible.
Inheritance
This condition is not inherited from a parent, and it cannot be passed down to children. It arises from somatic mutations in bone cells that occur spontaneously during an individual's lifetime.
Other Names for This Condition
- Candle wax disease
- Flowing hyperostosis
- Hyperostosis, monomelic
- Leri syndrome
- Leri's disease
- Melorheostoses
- Melorheostosis of Leri
- Melorheostosis, isolated
- Periostitis; monomelic
- Rheostosis