MCID: MLR003
MIFTS: 45

Melorheostosis

Categories: Bone diseases, Rare diseases, Skin diseases

Aliases & Classifications for Melorheostosis

MalaCards integrated aliases for Melorheostosis:

Name: Melorheostosis 12 52 25 29 54 15 71
Melorheostosis, Isolated 25
Hyperostosis, Monomelic 25
Melorheostosis of Leri 25
Periostitis; Monomelic 25
Flowing Hyperostosis 25
Candle Wax Disease 25
Leri's Disease 25
Melorheostoses 25
Leri Syndrome 25
Rheostosis 25

Classifications:



Summaries for Melorheostosis

NIH Rare Diseases : 52 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. 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. The diagnosis is based on a combination of clinical and radiological features, which are used to distinguish melorheostosis from other bone disorders. Isolated melorheostosis (with no other associated disorders) is typically sporadic, occurring in people with no family history of the condition. 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. In the remainder of cases, the cause is not yet known. Somatic mutations in other, unidentified genes may also cause the disorder. 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. Management depends on the severity and symptoms in each person and aims to relieve pain, correct deformity, and restore movement. Management options may include medications, physical therapy , occupational therapy, and/or orthopedic surgery. Melorheostosis is not life-threatening, but chronic pain can greatly impact quality of life.

MalaCards based summary : Melorheostosis, also known as melorheostosis, isolated, is related to buschke-ollendorff syndrome and osteopoikilosis. An important gene associated with Melorheostosis is LEMD3 (LEM Domain Containing 3), and among its related pathways/superpathways are Proteoglycans in cancer and VEGF Signaling. Affiliated tissues include bone, skin and cortex, and related phenotypes are skeletal dysplasia and joint stiffness

Disease Ontology : 12 An osteosclerosis that has material basis in a mutation of the LEMD3 gene which results in a hyperdense bony cortex.

Genetics Home Reference : 25 Melorheostosis is a rare bone disease. It causes the abnormal growth of new bone tissue on the surface of existing bones. The new bone has a characteristic appearance on x-rays, often described as "flowing" or like dripping candle wax. The excess bone growth typically occurs on the bones in one arm or leg, although it can also affect the pelvis, breastbone (sternum), ribs, or other bones. (The term "melorheostosis" is derived from the Greek words "melos," which means limb; "rheos," which means flow; and "ostosis," which refers to bone formation.) The abnormal bone growth associated with melorheostosis is noncancerous (benign), and it does not spread from one bone to another. The signs and symptoms of melorheostosis usually appear in childhood or adolescence. The condition can cause long-lasting (chronic) pain, permanent joint deformities (contractures), and a limited range of motion of the affected body part. In some people, the limb may appear thickened or enlarged, and the skin overlying the affected area can become red, thick, and shiny. Another rare disease, Buschke-Ollendorff syndrome, can include melorheostosis. Buschke-Ollendorff syndrome is characterized by skin growths called connective tissue nevi and areas of increased bone density called osteopoikilosis. A small percentage of affected individuals also have melorheostosis or other bone abnormalities. Scientists originally speculated that melorheostosis that occurs without the other features of Buschke-Ollendorff syndrome might have the same genetic cause as that syndrome. However, it has since been determined that Buschke-Ollendorff syndrome and melorheostosis that occurs alone are caused by mutations in different genes, and the two conditions are considered separate disorders.

Wikipedia : 74 Melorheostosis is a medical developmental disorder and mesenchymal dysplasia in which the bony cortex... more...

Related Diseases for Melorheostosis

Diseases related to Melorheostosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 114)
# Related Disease Score Top Affiliating Genes
1 buschke-ollendorff syndrome 31.9 SMAD2 SMAD1 LEXM LEMD3 EMD
2 osteopoikilosis 29.7 SMAD2 SMAD1 LEXM LEMD3 EMD
3 melorheostosis, isolated 12.8
4 melorheostosis with osteopoikilosis 12.8
5 roch-leri mesosomatous lipomatosis 11.6
6 hyperostosis 10.8
7 systemic scleroderma 10.6
8 bone disease 10.5
9 primary bone dysplasia with increased bone density 10.5
10 linear scleroderma 10.5
11 endosteal hyperostosis, autosomal dominant 10.3
12 myositis 10.2
13 osteogenic sarcoma 10.2
14 dysostosis 10.2
15 myositis ossificans 10.2
16 fibromatosis 10.2
17 neural tube defects 10.2
18 facial hemiatrophy 10.2
19 carpal tunnel syndrome 10.2
20 fibrous dysplasia 10.2
21 lymphangioma 10.2
22 hypertrichosis 10.2
23 neurofibromatosis 10.2
24 synovial chondromatosis 10.2
25 aneurysm 10.2
26 back pain 10.2
27 chronic pain 10.2
28 overgrowth syndrome 10.2
29 keloid disorder 10.1 CD36 BMP6
30 scleroderma, familial progressive 10.1 CD36 BMP6
31 lipomatosis, multiple 10.1
32 bone resorption disease 10.1
33 desmoid tumor 10.1
34 pleomorphic lipoma 10.1
35 nephrotic syndrome 10.1
36 osteopetrosis 10.1
37 hemangioma 10.1
38 radiculopathy 10.1
39 arthritis 10.1
40 neurofibroma 10.1
41 skeletal dysplasias 10.1
42 purpura 10.0
43 osteofibrous dysplasia 10.0 SPARC CD36
44 dupuytren contracture 10.0 FGF2 BMP6
45 juvenile nasopharyngeal angiofibroma 10.0 FGF2 BMP6
46 idiopathic hypercalciuria 10.0 FGF2 BMP6
47 hypertrophic scars 9.9 SMAD2 CD36 BMP6
48 renal cell carcinoma, nonpapillary 9.9
49 klippel-trenaunay-weber syndrome 9.9
50 nevus, epidermal 9.9

Graphical network of the top 20 diseases related to Melorheostosis:



Diseases related to Melorheostosis

Symptoms & Phenotypes for Melorheostosis

Human phenotypes related to Melorheostosis:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 skeletal dysplasia 31 hallmark (90%) HP:0002652
2 joint stiffness 31 hallmark (90%) HP:0001387
3 failure to thrive 31 hallmark (90%) HP:0001508
4 cranial nerve paralysis 31 hallmark (90%) HP:0006824
5 skeletal muscle atrophy 31 hallmark (90%) HP:0003202
6 arthralgia 31 hallmark (90%) HP:0002829
7 lymphedema 31 hallmark (90%) HP:0001004
8 increased bone mineral density 31 hallmark (90%) HP:0011001
9 hyperostosis 31 hallmark (90%) HP:0100774
10 ectopic ossification in muscle tissue 31 hallmark (90%) HP:0011987
11 bone pain 31 hallmark (90%) HP:0002653
12 lower limb asymmetry 31 frequent (33%) HP:0100559
13 upper limb asymmetry 31 frequent (33%) HP:0100560
14 arthritis 31 occasional (7.5%) HP:0001369
15 atypical scarring of skin 31 occasional (7.5%) HP:0000987
16 peripheral arteriovenous fistula 31 occasional (7.5%) HP:0100784

MGI Mouse Phenotypes related to Melorheostosis:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.86 CD36 EMD FGF2 LEMD3 MAP2K1 POSTN
2 cellular MP:0005384 9.81 CD36 EMD FGF2 LEMD3 LEXM MAP2K1
3 neoplasm MP:0002006 9.5 FGF2 LEXM MAP2K1 POSTN SMAD1 SMAD2
4 skeleton MP:0005390 9.23 BMP6 CD36 FGF2 MAP2K1 POSTN SMAD1

Drugs & Therapeutics for Melorheostosis

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of the Natural History, Pathogenesis and Outcome of Melorheostosis - a Rare Osteosclerotic Disease Recruiting NCT02504879
2 Screening and Diagnosis of Patients With Connective Tissue Disorders Recruiting NCT00076830

Search NIH Clinical Center for Melorheostosis

Genetic Tests for Melorheostosis

Genetic tests related to Melorheostosis:

# Genetic test Affiliating Genes
1 Melorheostosis 29

Anatomical Context for Melorheostosis

MalaCards organs/tissues related to Melorheostosis:

40
Bone, Skin, Cortex, Skeletal Muscle, Spinal Cord, Bone Marrow

Publications for Melorheostosis

Articles related to Melorheostosis:

(show top 50) (show all 424)
# Title Authors PMID Year
1
Melorheostosis: a Rare Sclerosing Bone Dysplasia. 61 52
28676968 2017
2
Melorheostosis: A Retrospective Clinical Analysis of 24 Patients at the Mayo Clinic. 61 52
27485676 2017
3
Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. 61 54
17087626 2007
4
MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. 54 61
15601644 2005
5
A multi-omics approach expands the mutational spectrum of MAP2K1-related melorheostosis. 61
32387835 2020
6
Somatic SMAD3-activating mutations cause melorheostosis by up-regulating the TGF-β/SMAD pathway. 61
32232430 2020
7
History of etidronate. 61
31911206 2020
8
Hide and seek: Somatic SMAD3 mutations in melorheostosis. 61
32289153 2020
9
Spinal Melorheostosis: A Rare Cause for Thoracic Radiculopathy. 61
32355627 2020
10
Melorheostosis of upper limb: A report of four rare cases. 61
32099304 2020
11
Monostotic melorheostosis and trigger finger. 61
32578577 2020
12
Bone Features of Unaffected Skeletal Sites in Melorheostosis: A Case Report. 61
32057643 2020
13
Re: Osteoma-like melorheostosis: a rare type of skeletal dysplasia depicted on FDG PET/CT. 61
31701180 2020
14
Constitutive activation of MEK1 in osteoprogenitors increases strength of bone despite impairing mineralization. 61
31689526 2020
15
Response to: letter to the editor re: Osteoma-like melorheostosis: a rare type of skeletal dysplasia depicted on FDG PET/CT. 61
31656975 2020
16
Melorheostosis: A Clinical, Pathologic, and Radiologic Case Series. 61
31386640 2019
17
A rare case of melorheostosis of the hand in a pediatric patient. 61
31528051 2019
18
Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study. 61
31485554 2019
19
Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series. 61
31129707 2019
20
Osteoma-like melorheostosis: a rare type of skeletal dysplasia depicted on FDG PET/CT. 61
30680447 2019
21
Melorheostosis Causing Compression of Common Peroneal Nerve at Fibular Tunnel. 61
31051308 2019
22
Melorheostosis: a rare sclerosing bone dysplasia. Usefulness of bone scintigraphy. 61
30975488 2019
23
Melorheostosis with an associated para-articular enhancing soft tissue mass. 61
30825667 2019
24
Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis. 61
30989250 2019
25
Melorheostosis in the pediatric hand. 61
31110758 2019
26
Melorheostotic Bone Lesions Caused by Somatic Mutations in MAP2K1 Have Deteriorated Microarchitecture and Periosteal Reaction. 61
30667555 2019
27
Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations. 61
30138550 2019
28
Melorheostosis in an Adolescent with Limb Length Discrepancy and Management with Epiphysiodesis with Eight Plates. 61
32547993 2019
29
CT analysis of anatomical distribution of melorheostosis challenges the sclerotome hypothesis. 61
30218789 2018
30
Structural basis for receptor-regulated SMAD recognition by MAN1. 61
30321401 2018
31
Melorheostosis of The Leg: A Case Report. 61
30647832 2018
32
Clinical improvement in a patient with monostotic melorheostosis after treatment with denosumab: a case report. 61
30257703 2018
33
Melorheostosis of a rib. 61
29997717 2018
34
Somatic activating mutations in MAP2K1 cause melorheostosis. 61
29643386 2018
35
Arthritis in Melorheostosis-An Uncommon Feature in a Rare Disease. 61
29108116 2018
36
Debridement arthroplasty of a rare case of elbow stiffness. A case report and literature review. 61
30312962 2018
37
Managing Recurrence in Intraarticular Melorheostosis Involving the Knee Joint: A Case Report. 61
29242791 2017
38
Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS. 61
28434888 2017
39
18F-NaF PET/CT in Extensive Melorheostosis of the Axial and Appendicular Skeleton With Soft-Tissue Involvement. 61
28319505 2017
40
Melorheostosis-Foot and ankle perspective. 61
28544914 2017
41
Melorheostosis with recurrent soft-tissue components: a histologically confirmed case. 61
28062900 2017
42
A Unique Case of Melorheostosis Presenting with Two Radiologically Distinct Lesions in the Shoulder. 61
29234550 2017
43
Pelvic Pain Due to Ischial Tuberosity and Acetabular Melorheostosis-Multimodal Image Presentation. 61
26968610 2016
44
Poster 442 Intractable Pelvic Pain Due to Melorheostosis Managed with Spinal Cord Stimulation: A Case Report. 61
27673191 2016
45
Sclerosing bone dysplasias: genetic, clinical and radiology update of hereditary and non-hereditary disorders. 61
26898950 2016
46
Characterization of hypertrophic osteoarthropathy in an identified skeleton from Évora, Portugal, using combined and comparative morphology and microscopy. 61
29539516 2016
47
Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT. 61
27252746 2016
48
Melorheostosis of the Foot: A Case Report of A rare entity with a Review of Multimodality Imaging Emphasizing the Importance of Conventional Radiography in Diagnosis. 61
27299136 2016
49
A skeletal case of hypertrophic osteoarthropathy from the Canary Islands dating from 1000 BP. 61
28802962 2015
50
Melorheostosis involving the hand. 61
25708729 2015

Variations for Melorheostosis

Expression for Melorheostosis

Search GEO for disease gene expression data for Melorheostosis.

Pathways for Melorheostosis

GO Terms for Melorheostosis

Cellular components related to Melorheostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 platelet alpha granule membrane GO:0031092 9.16 SPARC CD36
2 SMAD protein complex GO:0071141 8.96 SMAD2 SMAD1
3 nuclear inner membrane GO:0005637 8.8 SMAD1 LEMD3 EMD

Biological processes related to Melorheostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of gene expression GO:0010629 9.67 SMAD2 MAP2K1 FGF2 CD36
2 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.65 MAP2K1 FGF2 CD36
3 cellular response to BMP stimulus GO:0071773 9.46 SMAD1 BMP6
4 positive regulation of sprouting angiogenesis GO:1903672 9.43 SMAD1 FGF2
5 embryonic pattern specification GO:0009880 9.4 SMAD2 SMAD1
6 positive regulation of gene expression GO:0010628 9.35 SMAD2 SMAD1 MAP2K1 CD36 BMP6
7 SMAD protein signal transduction GO:0060395 9.33 SMAD2 SMAD1 BMP6
8 primary miRNA processing GO:0031053 9.32 SMAD2 SMAD1
9 SMAD protein complex assembly GO:0007183 9.26 SMAD2 SMAD1
10 wound healing GO:0042060 8.92 SPARC SMAD2 POSTN FGF2

Molecular functions related to Melorheostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 co-SMAD binding GO:0070410 9.26 SMAD2 SMAD1
2 I-SMAD binding GO:0070411 9.16 SMAD2 SMAD1
3 primary miRNA binding GO:0070878 8.96 SMAD2 SMAD1
4 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity GO:0030618 8.62 SMAD2 SMAD1

Sources for Melorheostosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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