Melorheostosis

Title

Categories:

Congenital and Genetic Diseases; Connective tissue diseases; Musculoskeletal Diseases

Summary Summary

Melorheostosis is a rare skeletal abnormality that causes abnormal growth of new bone tissue on top of existing bones. Signs and symptoms typically appear by late childhood or adolescence.^[1]^[2] Signs and symptoms may include deformity, contracture, chronic pain, stiffness, and limited range of motion. In some cases, the overlying skin and soft tissue may show thickening, shininess, reddening or darkening, linear scleroderma, and/or swelling. The condition typically affects the long bones, and the legs are affected more often than the arms. Sometimes the small bones of the hand or foot are affected, and rarely, bones of the skull or trunk are affected. The condition is sometimes associated with other bone or connective tissue abnormalities.^[2] The diagnosis is based on a combination of clinical and radiological features, which are used to distinguish melorheostosis from other bone disorders.^[3]

Isolated melorheostosis (with no other associated disorders) is typically sporadic, occurring in people with no family history of the condition.^[4] Around half of cases of isolated melorheostosis are due to acquired, somatic mutations in the MAP2K1 gene; these mutations are not inherited from a parent and occur randomly during a person's lifetime.^[4]^[5] In the remainder of cases, the cause is not yet known. Somatic mutations in other, unidentified genes may also cause the disorder.^[5] Some people with melorheostosis associated with other bone disorders (specifically osteopoikilosis and Buschke–Ollendorff syndrome) have heritable mutations in the LEMD3 gene, but mutations in this gene are not thought to be responsible for isolated melorheostosis.^[3]^[4]

Management depends on the severity and symptoms in each person and aims to relieve pain, correct deformity, and restore movement.^[6] Management options may include medications, physical therapy, occupational therapy, and/or orthopedic surgery.^[2]^[3] Melorheostosis is not life-threatening, but chronic pain can greatly impact quality of life.^[6]

Last updated: 5/29/2018

Symptoms Symptoms

Signs and symptoms of melorheostosis vary. Symptoms tend to appear by late childhood or early adulthood.^[1] The condition typically affects the long bones, and the legs are affected more often than the arms. Sometimes the small bones of the hand or foot are affected. Rarely it affects the spinal column, pelvis, skull, ribs, or other bones. It most often affects just one area of the body, but it can affect multiple areas.^[1]^[2]^[5]

Most people with melorheostosis have pain, which can be chronic (long-lasting) and may range from from dull to sharp and penetrating. Hardening of the skin and tissues around the affected bone can cause stiffness, and the involved skin may be tense, shiny, reddish, swollen, or with prominent veins.^[1]^[5] When melorheostosis involves a joint, it may result in a joint contracture (i.e., limited joint movement). Melorheostosis can also affect growth; for example, the affected limb can be shorter than the unaffected limb.^[1] If melorheostosis is associated with another bone disorder or syndrome, additional signs and symptoms may be present.

Last updated: 5/31/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 18 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Arthralgia	Joint pain	0002829
Bone pain		0002653
Cranial nerve paralysis		0006824
Ectopic ossification in muscle tissue	Calcification of muscle tissue	0011987
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Hyperostosis	Bone overgrowth	0100774
Increased bone mineral density	Increased bone density	0011001
Joint stiffness	Stiff joint Stiff joints [ more ]	0001387
Lymphedema	Swelling caused by excess lymph fluid under skin	0001004
Skeletal dysplasia		0002652
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
30%-79% of people have these symptoms
Lower limb asymmetry	Left and right leg differ in length or width	0100559
Upper limb asymmetry	Unequal size of arms	0100560
5%-29% of people have these symptoms
Arthritis	Joint inflammation	0001369
Atypical scarring of skin	Atypical scarring	0000987
Peripheral arteriovenous fistula		0100784
Percent of people who have these symptoms is not available through HPO
Progressive	Worsens with time	0003676
Sporadic	No previous family history	0003745

Showing of 18 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

There is no standard treatment for melorheostosis, and options are individualized based on the specific symptoms and severity in each person. Management aims to relieve pain, correct deformity, and restore movement.^[6] Physical therapy is an essential part of management both for pain relief and maintaining or improving range of motion. Other management options include bisphosphonates, pain medications, spinal cord stimulation, nerve blocks, and sympathectomy. Surgical options vary from person to person depending on the bone(s) and tissues involved and the severity.^[1]^[2]^[3]^[6] In some cases, bone deformities recur after surgical treatment.^[6]

Last updated: 5/29/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The main differential diagnoses include bone tumors generating dense bone such as osteosarcoma, as well as osteopathia striata, osteopoikilosis, myositis ossificans progressiva (see these terms) and osteoma. Rarely, in families with osteopoikilosis or Buschke-Ollendorf syndrome, patients with melorheostosis may be present (as seen in melorheostosis with osteopoikilosis) (see these terms). Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

The main differential diagnoses include bone tumors generating dense bone such as osteosarcoma, as well as osteopathia striata, osteopoikilosis, myositis ossificans progressiva (see these terms) and osteoma. Rarely, in families with osteopoikilosis or Buschke-Ollendorf syndrome, patients with melorheostosis may be present (as seen in melorheostosis with osteopoikilosis) (see these terms).

Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.
ClinicalTrials.gov lists trials that are related to Melorheostosis. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Melorheostosis Association
410 East 50th Street
New York, NY 10022
E-mail: Kathleen@harpervision.com; gordyjm@yahoo.com
Website: http://www.melorheostosis.com/

Social Networking Websites

Visit Melorheostosis Patients & Friends on Facebook.

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Melorheostosis. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Melorheostosis. Click on the link to view a sample search on this topic.

News & Events News & Events

News

NIH Researchers Discover Gene for Rare Disease of Excess Bone Tissue Growth
March 31, 2020

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

What is the prognosis or life expectancy for people diagnosed with melorheostosis? See answer

Have a question? Contact a GARD Information Specialist.

References References

Gagliardi GG, Mahan KT. Melorheostosis: a literature review and case report with surgical considerations. J Foot Ankle Surg. 2010 Jan-Feb; 49(1):80-5. Accessed 6/16/2015.
Smith GC, Pingree MJ, Freeman LA, et al. Melorheostosis: A Retrospective Clinical Analysis of 24 Patients at the Mayo Clinic. PM R. March, 2017; 9(3):283-288. https://www.ncbi.nlm.nih.gov/pubmed/27485676.
Kotwal A, Clarke BL. Melorheostosis: a Rare Sclerosing Bone Dysplasia. Curr Osteoporos Rep. August, 2017; 15(4):335-342. https://www.ncbi.nlm.nih.gov/pubmed/28676968.
Kang H, Jha S, Deng Z, et al. Somatic activating mutations in MAP2K1 cause melorheostosis. Nat Commun. April 11, 2018; 9(1):1390. https://www.nature.com/articles/s41467-018-03720-z.
Melorheostosis. Genetics Home Reference (GHR). May, 2018; https://ghr.nlm.nih.gov/condition/melorheostosis.
Mortier G. Melorheostosis. Orphanet. November, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2485.
Roger D, Bonnetblanc JM, Leroux-Robert C. Melorheostosis with associated minimal change nephrotic syndrome, mesenteric fibromatosis and capillary haemangiomas. Dermatology. 1994; 188:166-168. Accessed 6/17/2015.