The skeletal system is affected by melorheostosis, an enigmatic bone disorder. Characterised by irregular and excessive bone growth, this condition often leads to physical deformities and can have a significant impact on an individual's quality of life. Melorheostosis sheds light on the complicated processes underlying bone development and emphasises the importance of studying rare diseases.
Melorheostosis is a rare condition that commonly affects children and young adults. In this condition, one side of the affected bones gradually thickens, resulting in irregular and asymmetrical thickening. This gives the affected bones a "dripped candle wax" appearance on radiological imaging, which is where the name "melorheostosis" originates.
A mutation in mesenchymal stem cells, precursors of osteoblasts, the bone-forming cells, may be linked to melorheostosis. The excessive bone growth observed in this disorder may be caused by these mutations, causing abnormal signalling pathways.1,2
Causes of melorheostosis
Melorheostosis, often occurring on its own, can also be found in a few families with related syndromes like osteopoikilosis or Buschke-Ollendorff. These connections arise from changes in the LEMD3 gene. The disorder's random appearance and lack of inheritance led scientists to suspect post-conception DNA changes causing it, especially since bone problems localise. The recent confirmation comes from discoveries in the MAP2K1 and SMAD3 genes, suggesting other genes could also be involved. These genetic shifts occur post-conception and do not pass from parents.
Clinical signs of melorheostosis vary, depending on the bone's extent and location. Affected bones can thicken and deform, causing limb differences and limiting joint movement, causing pain. Common spots include arms, legs, hands, feet, and severe cases might affect the spine, leading to curvature and nerve issues.
While melorheostosis's exact cause is being studied, recent research has spotted a genetic link. MAP2K1 gene mosaic mutations appear in some cases. These changes aren't inherited but happen spontaneously in some cells during early development, leading to the observed bone issues.3
Symptoms of melorheostosis
- Pain, stiffness, and limited joint movement or deformity are common initial symptoms.
- Gradual onset of symptoms, ranging from none to severe deformities caused by contracture.
- Observations may include cranial nerve paralysis, misplaced bone formation in muscles, increased bone density, and excessive bone growth (hyperostosis).
- Uneven muscle size and asymmetry in the upper and lower limbs.
- Bone involvement can be in one or multiple bones, often limited to a single limb, but can affect both sides.
- Uneven limb length due to uneven growth plate fusion.
- Early onset and involvement of multiple limbs might indicate a higher risk of complications.
- Characterized by irregular thickening of cortical bone, resembling "melted wax flowing down a candle" in classic cases.
Diagnosing melorheostosis can be challenging due to its rarity and variable presentation. Radiological imaging plays a crucial role in diagnosis, with X-rays, CT scans, and MRI helping to visualise characteristic bone changes. In some cases, a histopathological examination of affected bone tissue may be necessary to confirm the diagnosis.4
- Clinical Procedures: Healthcare providers often suggest clinical procedures for diagnosing issues. These tests vary based on the body system. Different professionals, like nurses, physician assistants, and lab technicians, perform these outpatient procedures. Referrals from your primary care provider (PCP) are usually needed.
- Laboratory Tests: Healthcare providers use lab tests to diagnose diseases by examining blood, urine, or tissues based on symptoms and possible conditions.
- Imaging studies: Imaging studies to diagnose or manage a disease is recommended by a doctor. These studies allow doctors to examine the body internally to identify disease clues. The choice of imaging depends on symptoms and the specific body area.5
Management and treatment
Currently, there is no cure for melorheostosis. Treatment focuses on managing symptoms and improving quality of life. Pain management strategies, physical therapy and assistive devices are often used to address pain and functional limitations. Surgical interventions may be considered in severe cases to alleviate pain, correct deformities and improve joint function.
Research is ongoing to explore potential targeted therapies that could inhibit the abnormal signalling pathways responsible for excessive bone growth. These emerging therapies hold promise for more effective and focused treatments in the future.
Living with melorheostosis can pose significant challenges, both physical and emotional. Individuals affected by this disorder may experience pain, limited mobility and body image concerns due to visible deformities. Coping mechanisms, support networks and access to specialised medical care play vital roles in helping individuals manage the impacts of melorheostosis on their daily lives. https://rarediseases.org/rare-diseases/melorheostosis/#therapies
What are alternative names for melorheostosis?
Melorheostosis, also known as candle bone disease, melting wax syndrome or Leri disease, was initially identified by Leri and Joanny in 1922. It's a rare non-cancerous bone condition categorized as benign sclerosing bone dysplasia, marked by mesodermal bone dysplasia.
How common is melorheostosis?
About 1 out of every 1 million people suffer from melorheostosis, affecting genders equally. Globally, 400 cases have been reported. Melorheostosis manifests itself with symptoms like pain, joint stiffness, deformities and differences in limb length. On X-rays, it displays a unique look similar to melted wax running along the sides of a candle.6
What is the age at the onset of melorheostosis?
The age of onset of melorheostosis varies, but symptoms typically start showing during late childhood or adolescence.
Is melorheostosis a severe condition?
Melorheostosis impacts the growth and development of bones and soft tissues. While it is not cancerous, this disorder can lead to significant functional restrictions, chronic pain, joint tightness and deformities in the limbs, hands, or feet.
What is a differential diagnosis for melorheostosis?
A differential diagnosis of melorheostosis involves considering conditions that share similar symptoms or features. These conditions include:
- Buschke-Ollendorff Syndrome
- Osteopathic Striata7
- Linear Scleroderma
- Desmoid Tumors
Distinguishing between these conditions relies on clinical features, imaging studies and specific diagnostic criteria.
Can melorheostosis be treated?
While there is no complete cure for melorheostosis, treatments are available to help manage its symptoms. Healthcare providers might recommend strategies to alleviate pain and enhance function. These could include interventions like physical therapy aimed at strengthening muscles and improving flexibility.
Other conditions similar to melorheostosis
Conditions that share similar symptoms with melorheostosis include:
- Osteopoikilosis: A rare bone disorder where there are rounded or oval areas of increased bone density at the ends of long bones. These areas are often on both sides of the body.
- Buschke-Ollendorff Syndrome: A hereditary condition involving both skin growths (connective tissue nevi) and osteopoikilosis.
- Osteopathia Striata: A benign bone disorder with longitudinal "stripes" of increased density in affected bones.
- Linear Scleroderma: Characterized by band-like skin thickening in the arms and legs, which can cause one limb to grow slower than the other.
- Desmoid Tumors: Tumors that grow in fibrous tissues, like tendons or ligaments, and can be invasive and difficult to control.
- Haemangiomas: Growth of small blood vessels appearing in infancy, usually as skin growths.5
Melorheostosis is an unusual bone problem where extra bone tissue grows on top of existing bones. Symptoms usually start showing during the late childhood or teenage years. These can include deformities, stiffness, pain, limited movement and tightening of the skin and soft tissue, which might become thicker, shinier, redder or swollen. This condition usually affects long bones, with legs being more commonly affected than arms. Sometimes, smaller hand or foot bones are involved, and very rarely, it can affect the skull or trunk bones. It might also be linked to other bone or connective tissue issues. The diagnosis relies on both clinical and imaging features to differentiate it from other bone disorders.
Isolated melorheostosis, where there are no other related issues, usually happens in individuals without a family history of the condition. In about half of these cases, changes in the MAP2K1 gene, occurring randomly during a person's lifetime and not inherited, are responsible. The cause in the remaining cases is still unknown.
- Kumar R, Sankhala SS, Bijarnia I. Melorheostosis - Case Report of Rare Disease. J Orthop Case Rep. 2014 Apr-Jun;4(2):25-7. doi: 10.13107/jocr.2250-0685.162. PMID: 27298954; PMCID: PMC4719368.
- Clinical Imaging [Internet]. Elsevier; 2014 [cited 2023 Nov 20]. Available from: https://linkinghub.elsevier.com/retrieve/pii/C20090428009.
- Melorheostosis - Symptoms, Causes, Treatment | NORD [Internet]. [cited 2023 Aug 14]. Available from: https://rarediseases.org/rare-diseases/melorheostosis/.
- Gurcan MN, Boucheron LE, Can A, Madabhushi A, Rajpoot NM, Yener B. Histopathological image analysis: a review. IEEE Rev Biomed Eng. 2009;2:147-71. doi: 10.1109/RBME.2009.2034865. Epub 2009 Oct 30. PMID: 20671804; PMCID: PMC2910932.
- Melorheostosis - getting a diagnosis [Internet]. U.S. Department of Health and Human Services; [cited 2023 Nov 20]. Available from: https://rarediseases.info.nih.gov/diseases/9474/melorheostosis/diagnosis.
- Ambatkar SY, Rudey MD. Melorheostosis - a rare and progressive disease. Pan Afr Med J. 2023 Feb 6;44:69.
- Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.