Rare Nephrology News

Disease Profile

Melorheostosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

All ages

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ICD-10

M85.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Congenital and Genetic Diseases; Connective tissue diseases; Musculoskeletal Diseases

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]

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.

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.

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

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

    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]

    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

      Social Networking Websites

        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.

            References

            1. 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.
            2. 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.
            3. 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.
            4. 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.
            5. Melorheostosis. Genetics Home Reference (GHR). May, 2018; https://ghr.nlm.nih.gov/condition/melorheostosis.
            6. Mortier G. Melorheostosis. Orphanet. November, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2485.
            7. 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.

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