MCID: MLR003
MIFTS: 48

Melorheostosis

Categories: Bone diseases, Rare diseases, Skin diseases

Aliases & Classifications for Melorheostosis

MalaCards integrated aliases for Melorheostosis:

Name: Melorheostosis 12 20 43 29 54 6 44 15 70
Melorheostosis, Isolated 43
Hyperostosis, Monomelic 43
Melorheostosis of Leri 43
Periostitis; Monomelic 43
Flowing Hyperostosis 43
Candle Wax Disease 43
Leri's Disease 43
Melorheostoses 43
Leri Syndrome 43
Rheostosis 43

Classifications:



Summaries for Melorheostosis

GARD : 20 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 MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1), and among its related pathways/superpathways are TGF-Beta Pathway and Pathways in cancer. Affiliated tissues include bone, cortex and skeletal muscle, and related phenotypes are failure to thrive and skeletal dysplasia

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

MedlinePlus Genetics : 43 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 : 73 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 117)
# Related Disease Score Top Affiliating Genes
1 buschke-ollendorff syndrome 32.0 SMAD2 SMAD1 LEMD3 EMD
2 osteopoikilosis 30.3 SMAD2 SMAD1 MAP2K1 LEMD3 EMD
3 melorheostosis, isolated 11.6
4 melorheostosis with osteopoikilosis 11.6
5 roch-leri mesosomatous lipomatosis 11.1
6 hyperostosis 10.7
7 systemic scleroderma 10.5
8 bone disease 10.4
9 primary bone dysplasia with increased bone density 10.4
10 linear scleroderma 10.4
11 autosomal dominant non-syndromic intellectual disability 19 10.2 SMAD3 SMAD2
12 loeys-dietz syndrome 5 10.2 SMAD3 SMAD2
13 albinism, ocular, with late-onset sensorineural deafness 10.2 SMAD3 SMAD2
14 nephrogenic systemic fibrosis 10.2 SMAD3 SMAD2
15 loeys-dietz syndrome 3 10.2 SMAD3 SMAD2
16 myositis 10.1
17 dysostosis 10.1
18 osteochondrodysplasia 10.1
19 myositis ossificans 10.1
20 loeys-dietz syndrome 4 10.1 SMAD3 SMAD2
21 emery-dreifuss muscular dystrophy 1, x-linked 10.1 LEMD3 EMD
22 keloid disorder 10.1 CD36 BMP6
23 scleroderma, familial progressive 10.1 CD36 BMP6
24 osteogenic sarcoma 10.1
25 hypertrichosis 10.1
26 fibromatosis 10.1
27 synovial chondromatosis 10.1
28 spinal muscular atrophy, type ii 10.1 SMAD3 SMAD2 SMAD1
29 dupuytren contracture 10.1 FGF2 BMP6
30 spastic paraplegia 3, autosomal dominant 10.0 SMAD3 SMAD2 POSTN
31 juvenile nasopharyngeal angiofibroma 10.0 FGF2 BMP6
32 carpal tunnel syndrome 10.0
33 fibrous dysplasia 10.0
34 neurofibromatosis 10.0
35 aneurysm 10.0
36 overgrowth syndrome 10.0
37 osteofibrous dysplasia 10.0 SPARC CD36
38 idiopathic hypercalciuria 10.0 FGF2 BMP6
39 greenberg dysplasia 10.0 LEMD3 EMD
40 neural tube defects 9.9
41 facial hemiatrophy 9.9
42 lipomatosis, multiple 9.9
43 nevus, epidermal 9.9
44 dowling-degos disease 1 9.9
45 bone resorption disease 9.9
46 desmoid tumor 9.9
47 pleomorphic lipoma 9.9
48 nephrotic syndrome 9.9
49 telangiectasis 9.9
50 osteopetrosis 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 failure to thrive 31 hallmark (90%) HP:0001508
2 skeletal dysplasia 31 hallmark (90%) HP:0002652
3 joint stiffness 31 hallmark (90%) HP:0001387
4 cranial nerve paralysis 31 hallmark (90%) HP:0006824
5 skeletal muscle atrophy 31 hallmark (90%) HP:0003202
6 lymphedema 31 hallmark (90%) HP:0001004
7 arthralgia 31 hallmark (90%) HP:0002829
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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.97 CD36 EMD FGF2 LEMD3 MAP2K1 POSTN
2 cellular MP:0005384 9.91 CD36 EMD FGF2 LEMD3 MAP2K1 POSTN
3 craniofacial MP:0005382 9.63 MAP2K1 POSTN SMAD1 SMAD2 SMAD3 SPARC
4 neoplasm MP:0002006 9.5 FGF2 MAP2K1 POSTN SMAD1 SMAD2 SMAD3
5 skeleton MP:0005390 9.28 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 Investigations of Bone-Related Connective Tissue Disorders Recruiting NCT00076830

Search NIH Clinical Center for Melorheostosis

Cochrane evidence based reviews: 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, Cortex, Skeletal Muscle, Spinal Cord, Bone Marrow, Heart, Ovary

Publications for Melorheostosis

Articles related to Melorheostosis:

(show top 50) (show all 438)
# Title Authors PMID Year
1
Melorheostosis: a Rare Sclerosing Bone Dysplasia. 61 20
28676968 2017
2
Melorheostosis: A Retrospective Clinical Analysis of 24 Patients at the Mayo Clinic. 61 20
27485676 2017
3
Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. 54 61
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
Meralgia Paresthetica Caused by Melorheostosis Affecting the Ipsilateral Ilium: A Case Report. 61
33798122 2021
6
A systematic review of the clinical and radiographic features of hybrid central giant cell granuloma lesions of the jaws. 61
32730731 2021
7
Distribution and Functional Consequences of Somatic MAP2K1 Variants in Affected Skin Associated with Bone Lesions in Melorheostosis. 61
32791068 2021
8
Open Excision of Olecranon Melorheostosis to Relieve Elbow Extension Block. 61
33648811 2021
9
Axial melorheostosis: A rare presentation. 61
32994853 2020
10
Bone Features of Unaffected Skeletal Sites in Melorheostosis: A Case Report. 61
32057643 2020
11
A rare case of melorheostosis with intra-articular extension causing medial patellar impingement. 61
33737781 2020
12
A Highly Unusual Clinical Presentation and Imaging Appearance of a Rare Diseases: Melorheostosis. 61
33489974 2020
13
Case of melorheostosis associated with ipsilateral verrucous epidermal nevus, linear connective tissue nevus, diffuse hyperpigmentation and hypertrichosis: A fortuitous coincidence? 61
32656852 2020
14
A multi-omics approach expands the mutational spectrum of MAP2K1-related melorheostosis. 61
32387835 2020
15
A Rare Case of Melorheostosis in the Hand of a Saudi Woman. 61
32626632 2020
16
Somatic SMAD3-activating mutations cause melorheostosis by up-regulating the TGF-β/SMAD pathway. 61
32232430 2020
17
History of etidronate. 61
31911206 2020
18
Hide and seek: Somatic SMAD3 mutations in melorheostosis. 61
32289153 2020
19
Spinal Melorheostosis: A Rare Cause for Thoracic Radiculopathy. 61
32355627 2020
20
Melorheostosis of upper limb: A report of four rare cases. 61
32099304 2020
21
Constitutive activation of MEK1 in osteoprogenitors increases strength of bone despite impairing mineralization. 61
31689526 2020
22
The dripping candle wax sign of melorheostosis. 61
32922791 2020
23
Monostotic melorheostosis and trigger finger. 61
32578577 2020
24
Response to: letter to the editor re: Osteoma-like melorheostosis: a rare type of skeletal dysplasia depicted on FDG PET/CT. 61
31656975 2020
25
Re: Osteoma-like melorheostosis: a rare type of skeletal dysplasia depicted on FDG PET/CT. 61
31701180 2020
26
Melorheostosis: A Clinical, Pathologic, and Radiologic Case Series. 61
31386640 2019
27
A rare case of melorheostosis of the hand in a pediatric patient. 61
31528051 2019
28
Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study. 61
31485554 2019
29
Melorheostosis Causing Compression of Common Peroneal Nerve at Fibular Tunnel. 61
31051308 2019
30
Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series. 61
31129707 2019
31
Osteoma-like melorheostosis: a rare type of skeletal dysplasia depicted on FDG PET/CT. 61
30680447 2019
32
Melorheostosis: a rare sclerosing bone dysplasia. Usefulness of bone scintigraphy. 61
30975488 2019
33
Melorheostosis with an associated para-articular enhancing soft tissue mass. 61
30825667 2019
34
Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis. 61
30989250 2019
35
Melorheostosis in the pediatric hand. 61
31110758 2019
36
Melorheostotic Bone Lesions Caused by Somatic Mutations in MAP2K1 Have Deteriorated Microarchitecture and Periosteal Reaction. 61
30667555 2019
37
Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations. 61
30138550 2019
38
Melorheostosis in an Adolescent with Limb Length Discrepancy and Management with Epiphysiodesis with Eight Plates. 61
32547993 2019
39
CT analysis of anatomical distribution of melorheostosis challenges the sclerotome hypothesis. 61
30218789 2018
40
Structural basis for receptor-regulated SMAD recognition by MAN1. 61
30321401 2018
41
Melorheostosis of The Leg: A Case Report. 61
30647832 2018
42
Clinical improvement in a patient with monostotic melorheostosis after treatment with denosumab: a case report. 61
30257703 2018
43
Melorheostosis of a rib. 61
29997717 2018
44
Somatic activating mutations in MAP2K1 cause melorheostosis. 61
29643386 2018
45
Arthritis in Melorheostosis-An Uncommon Feature in a Rare Disease. 61
29108116 2018
46
Debridement arthroplasty of a rare case of elbow stiffness. A case report and literature review. 61
30312962 2018
47
Managing Recurrence in Intraarticular Melorheostosis Involving the Knee Joint: A Case Report. 61
29242791 2017
48
Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS. 61
28434888 2017
49
18F-NaF PET/CT in Extensive Melorheostosis of the Axial and Appendicular Skeleton With Soft-Tissue Involvement. 61
28319505 2017
50
Melorheostosis-Foot and ankle perspective. 61
28544914 2017

Variations for Melorheostosis

ClinVar genetic disease variations for Melorheostosis:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MAP2K1 NM_002755.4(MAP2K1):c.389A>G (p.Tyr130Cys) SNV Pathogenic 13351 rs121908595 GRCh37: 15:66729181-66729181
GRCh38: 15:66436843-66436843

Expression for Melorheostosis

Search GEO for disease gene expression data for Melorheostosis.

Pathways for Melorheostosis

Pathways related to Melorheostosis according to GeneCards Suite gene sharing:

(show all 31)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.36 SMAD3 SMAD2 SMAD1 MAP2K1 FGF2 BMP6
2 12.66 SMAD3 SMAD2 MAP2K1 FGF2
3
Show member pathways
12.57 SMAD3 SMAD2 MAP2K1 FGF2
4
Show member pathways
12.24 SMAD3 SMAD2 SMAD1 FGF2
5 12.14 SMAD2 MAP2K1 FGF2
6 12 SMAD3 SMAD2 MAP2K1
7 11.96 SMAD3 SMAD2 MAP2K1
8 11.9 SMAD3 SMAD2 SMAD1 BMP6
9 11.89 SMAD3 SMAD2 MAP2K1
10 11.86 SMAD3 SMAD2 MAP2K1
11 11.74 SPARC SMAD3 MAP2K1
12 11.68 SPARC FGF2 BMP6
13
Show member pathways
11.65 SMAD3 SMAD2 SMAD1
14 11.6 SMAD3 SMAD2 SMAD1 MAP2K1
15 11.53 SMAD3 SMAD2 BMP6
16 11.53 SMAD3 SMAD2 SMAD1 BMP6
17 11.51 SMAD3 SMAD2 MAP2K1
18 11.51 SMAD3 SMAD2 SMAD1 MAP2K1 FGF2
19 11.45 SMAD3 SMAD2 MAP2K1
20
Show member pathways
11.41 SMAD3 SMAD2 MAP2K1
21 11.37 SMAD3 SMAD2 SMAD1
22 11.36 SPARC SMAD3 SMAD2 SMAD1 EMD BMP6
23 11.3 SMAD3 SMAD2 SMAD1 MAP2K1
24
Show member pathways
11.17 LEMD3 EMD
25 11.13 SMAD3 SMAD2
26 11.1 SMAD3 SMAD2
27 11.03 SMAD2 FGF2
28 10.99 SMAD1 FGF2
29 10.94 SMAD3 SMAD2 POSTN
30 10.86 SMAD3 SMAD2
31 10.82 SMAD3 SMAD2

GO Terms for Melorheostosis

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10 SPARC SMAD3 SMAD2 SMAD1 POSTN MAP2K1
2 nuclear inner membrane GO:0005637 9.46 SMAD3 SMAD1 LEMD3 EMD
3 platelet alpha granule membrane GO:0031092 9.32 SPARC CD36
4 heteromeric SMAD protein complex GO:0071144 9.13 SMAD3 SMAD2 SMAD1
5 SMAD protein complex GO:0071141 8.8 SMAD3 SMAD2 SMAD1

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

(show all 31)
# Name GO ID Score Top Affiliating Genes
1 cell differentiation GO:0030154 10.04 SMAD3 SMAD2 SMAD1 FGF2 BMP6
2 negative regulation of cell proliferation GO:0008285 9.92 SMAD3 SMAD2 SMAD1 MAP2K1
3 negative regulation of gene expression GO:0010629 9.87 SMAD2 MAP2K1 FGF2 CD36
4 anatomical structure morphogenesis GO:0009653 9.79 SMAD3 SMAD2 SMAD1
5 transforming growth factor beta receptor signaling pathway GO:0007179 9.75 SMAD3 SMAD2 SMAD1
6 lung development GO:0030324 9.73 SPARC SMAD2 FGF2
7 negative regulation of transforming growth factor beta receptor signaling pathway GO:0030512 9.71 SMAD3 SMAD2 LEMD3
8 BMP signaling pathway GO:0030509 9.67 SMAD3 SMAD2 SMAD1 BMP6
9 positive regulation of sprouting angiogenesis GO:1903672 9.65 SMAD1 FGF2
10 endoderm development GO:0007492 9.65 SMAD3 SMAD2
11 positive regulation of pri-miRNA transcription by RNA polymerase II GO:1902895 9.65 SMAD3 SMAD1 FGF2
12 developmental growth GO:0048589 9.64 SMAD3 SMAD2
13 regulation of transforming growth factor beta receptor signaling pathway GO:0017015 9.63 SMAD3 SMAD2
14 thyroid gland development GO:0030878 9.63 SMAD3 MAP2K1
15 ureteric bud development GO:0001657 9.63 SMAD3 SMAD2 SMAD1
16 SMAD protein signal transduction GO:0060395 9.62 SMAD3 SMAD2 SMAD1 BMP6
17 negative regulation of wound healing GO:0061045 9.61 SMAD3 FGF2
18 activin receptor signaling pathway GO:0032924 9.61 SMAD3 SMAD2
19 adrenal gland development GO:0030325 9.6 SMAD3 SMAD2
20 signal transduction involved in regulation of gene expression GO:0023019 9.59 SMAD3 SMAD2
21 positive regulation of chondrocyte differentiation GO:0032332 9.58 SMAD3 BMP6
22 embryonic pattern specification GO:0009880 9.58 SMAD3 SMAD2 SMAD1
23 nodal signaling pathway GO:0038092 9.55 SMAD3 SMAD2
24 pericardium development GO:0060039 9.52 SMAD3 SMAD2
25 embryonic foregut morphogenesis GO:0048617 9.51 SMAD3 SMAD2
26 positive regulation of gene expression GO:0010628 9.5 SMAD3 SMAD2 SMAD1 MAP2K1 FGF2 CD36
27 regulation of binding GO:0051098 9.49 SMAD3 SMAD2
28 paraxial mesoderm morphogenesis GO:0048340 9.43 SMAD3 SMAD2
29 primary miRNA processing GO:0031053 9.43 SMAD3 SMAD2 SMAD1
30 SMAD protein complex assembly GO:0007183 9.33 SMAD3 SMAD2 SMAD1
31 wound healing GO:0042060 9.02 SPARC SMAD3 SMAD2 POSTN FGF2

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

# Name GO ID Score Top Affiliating Genes
1 R-SMAD binding GO:0070412 9.32 SMAD3 SMAD2
2 transforming growth factor beta receptor binding GO:0005160 9.26 SMAD3 SMAD2
3 DEAD/H-box RNA helicase binding GO:0017151 9.16 SMAD3 SMAD1
4 I-SMAD binding GO:0070411 9.13 SMAD3 SMAD2 SMAD1
5 co-SMAD binding GO:0070410 8.8 SMAD3 SMAD2 SMAD1

Sources for Melorheostosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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