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Melorheostosis(MEL)

MedGen UID:
460981
Concept ID:
C3149631
Disease or Syndrome
Synonyms: MEL; MELORHEOSTOSIS, ISOLATED
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): MAP2K1 (15q22.31)
 
HPO: HP:6000817
Monarch Initiative: MONDO:0007970
OMIM®: 155950
Orphanet: ORPHA2485

Definition

Melorheostosis (MEL) is characterized by 'flowing' hyperostosis of the cortex of tubular bones. The lesions are usually asymmetric and involve only 1 limb or correspond to a particular sclerotome. They may be accompanied by abnormalities of adjacent soft tissue, including joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangiomas (review by Hellemans et al., 2004). The designation combines root words meaning 'limb,' 'flow,' and 'bone.' Melorheostosis may sometimes be a feature of Buschke-Ollendorff syndrome (BOS; 166700), a benign disorder which is caused by mutation in the LEMD3 gene (607844). Although germline or somatic LEMD3 mutations had been postulated to cause isolated melorheostosis (Butkus et al., 1997; Debeer et al., 2003; Happle, 2004; Hellemans et al., 2004), several studies have not been able to prove this (Hellemans et al., 2004; Mumm et al., 2007; Zhang et al., 2009). [from OMIM]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/melorheostosis

Clinical features

From HPO
Hyperostosis
MedGen UID:
9366
Concept ID:
C0020492
Disease or Syndrome
Excessive growth or abnormal thickening of bone tissue.
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often referred to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Melorheostosis
MedGen UID:
460981
Concept ID:
C3149631
Disease or Syndrome
Melorheostosis (MEL) is characterized by 'flowing' hyperostosis of the cortex of tubular bones. The lesions are usually asymmetric and involve only 1 limb or correspond to a particular sclerotome. They may be accompanied by abnormalities of adjacent soft tissue, including joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangiomas (review by Hellemans et al., 2004). The designation combines root words meaning 'limb,' 'flow,' and 'bone.' Melorheostosis may sometimes be a feature of Buschke-Ollendorff syndrome (BOS; 166700), a benign disorder which is caused by mutation in the LEMD3 gene (607844). Although germline or somatic LEMD3 mutations had been postulated to cause isolated melorheostosis (Butkus et al., 1997; Debeer et al., 2003; Happle, 2004; Hellemans et al., 2004), several studies have not been able to prove this (Hellemans et al., 2004; Mumm et al., 2007; Zhang et al., 2009).

Conditions with this feature

Dermatofibrosis lenticularis disseminata
MedGen UID:
120545
Concept ID:
C0265514
Disease or Syndrome
Buschke-Ollendorff syndrome (BOS) is an autosomal dominant connective tissue disorder manifest by multiple subcutaneous nevi or nodules. They may be either elastin-rich (elastoma) or collagen-rich (dermatofibrosis lenticularis disseminata) on histologic examination. The lesions are usually nontender and firm. Affected individuals also have osteopoikilosis (OPK), literally meaning 'spotted bones,' which are osteosclerotic foci that occur in the epiphyses and metaphyses of long bones, wrist, foot, ankle, pelvis, and scapula. Some individuals have both skin and bone manifestations, whereas others may lack skin or bone manifestations. Some individuals may also have melorheostosis (155950), which is characterized by 'flowing' hyperostosis of the cortex of tubular bones. Most reported cases of BOS and OPK are benign, and the bone lesions are found incidentally, although some patients may have joint pain (reviews by Hellemans et al., 2004 and Zhang et al., 2009).
Melorheostosis
MedGen UID:
460981
Concept ID:
C3149631
Disease or Syndrome
Melorheostosis (MEL) is characterized by 'flowing' hyperostosis of the cortex of tubular bones. The lesions are usually asymmetric and involve only 1 limb or correspond to a particular sclerotome. They may be accompanied by abnormalities of adjacent soft tissue, including joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangiomas (review by Hellemans et al., 2004). The designation combines root words meaning 'limb,' 'flow,' and 'bone.' Melorheostosis may sometimes be a feature of Buschke-Ollendorff syndrome (BOS; 166700), a benign disorder which is caused by mutation in the LEMD3 gene (607844). Although germline or somatic LEMD3 mutations had been postulated to cause isolated melorheostosis (Butkus et al., 1997; Debeer et al., 2003; Happle, 2004; Hellemans et al., 2004), several studies have not been able to prove this (Hellemans et al., 2004; Mumm et al., 2007; Zhang et al., 2009).

Professional guidelines

PubMed

Jain VK, Arya RK, Bharadwaj M, Kumar S
Orthopedics 2009 Jul;32(7):512. doi: 10.3928/01477447-20090527-20. PMID: 19634844

Recent clinical studies

Etiology

Giardullo L, Altomare A, Rotondo C, Corrado A, Cantatore FP
Int J Mol Sci 2021 Jul 26;22(15) doi: 10.3390/ijms22157980. PMID: 34360745Free PMC Article
Wordsworth P, Chan M
Calcif Tissue Int 2019 May;104(5):530-543. Epub 2019 Apr 15 doi: 10.1007/s00223-019-00543-y. PMID: 30989250
De Ridder R, Boudin E, Mortier G, Van Hul W
Curr Osteoporos Rep 2018 Jun;16(3):256-268. doi: 10.1007/s11914-018-0439-7. PMID: 29656376
Dhillon MS, Saibaba B
Foot (Edinb) 2017 Jun;31:44-48. Epub 2017 Mar 1 doi: 10.1016/j.foot.2017.02.004. PMID: 28544914
Foti R, Leonardi R, Rondinone R, Di Gangi M, Leonetti C, Canova M, Doria A
Autoimmun Rev 2008 Feb;7(4):331-9. Epub 2008 Jan 11 doi: 10.1016/j.autrev.2007.12.004. PMID: 18295739

Diagnosis

Wordsworth P, Chan M
Calcif Tissue Int 2019 May;104(5):530-543. Epub 2019 Apr 15 doi: 10.1007/s00223-019-00543-y. PMID: 30989250
Kotwal A, Clarke BL
Curr Osteoporos Rep 2017 Aug;15(4):335-342. doi: 10.1007/s11914-017-0375-y. PMID: 28676968
Allen GM
Semin Musculoskelet Radiol 2011 Jul;15(3):247-56. Epub 2011 Jun 3 doi: 10.1055/s-0031-1278424. PMID: 21644198
de Vernejoul MC
Best Pract Res Clin Rheumatol 2008 Mar;22(1):71-83. doi: 10.1016/j.berh.2007.12.011. PMID: 18328982
Rozencwaig R, Wilson MR, McFarland GB Jr
Am J Orthop (Belle Mead NJ) 1997 Feb;26(2):83-9. PMID: 9040882

Therapy

Iordache S, Cursaru A, Serban B, Costache M, Spiridonica R, Cretu B, Cirstoiu C
Medicina (Kaunas) 2023 Apr 30;59(5) doi: 10.3390/medicina59050869. PMID: 37241101Free PMC Article
Farrell K, Comis LE, Casimir MM, Hodsdon B, Jiménez-Silva R, Dunigan T, Bhattacharyya T, Jha S
PM R 2023 May;15(5):587-595. Epub 2022 May 30 doi: 10.1002/pmrj.12817. PMID: 35403375Free PMC Article
Watts NB, Chesnut CH 3rd, Genant HK, Harris ST, Jackson RD, Licata AA, Miller PD, Mysiw WJ, Richmond B, Valent D
Bone 2020 May;134:115222. Epub 2020 Jan 3 doi: 10.1016/j.bone.2020.115222. PMID: 31911206
Jha S, Fratzl-Zelman N, Roschger P, Papadakis GZ, Cowen EW, Kang H, Lehky TJ, Alter K, Deng Z, Ivovic A, Flynn L, Reynolds JC, Dasgupta A, Miettinen M, Lange E, Katz J, Klaushofer K, Marini JC, Siegel RM, Bhattacharyya T
J Bone Miner Res 2019 Jan;34(1):145-156. Epub 2018 Sep 14 doi: 10.1002/jbmr.3577. PMID: 30138550Free PMC Article
Alothman M, Alkhamees L, Al Subaie AM
J Radiol Case Rep 2018 Nov;12(11):12-17. Epub 2018 Nov 30 doi: 10.3941/jrcr.v12i11.3539. PMID: 30647832Free PMC Article

Prognosis

Iordache S, Cursaru A, Serban B, Costache M, Spiridonica R, Cretu B, Cirstoiu C
Medicina (Kaunas) 2023 Apr 30;59(5) doi: 10.3390/medicina59050869. PMID: 37241101Free PMC Article
Tekin L, Akarsu S, Durmuş O, Kiralp MZ
Am J Phys Med Rehabil 2012 Jan;91(1):96. doi: 10.1097/PHM.0b013e318224166b. PMID: 21849883
Foti R, Leonardi R, Rondinone R, Di Gangi M, Leonetti C, Canova M, Doria A
Autoimmun Rev 2008 Feb;7(4):331-9. Epub 2008 Jan 11 doi: 10.1016/j.autrev.2007.12.004. PMID: 18295739
Ethunandan M, Khosla N, Tilley E, Webb A
J Craniofac Surg 2004 Nov;15(6):1062-5. doi: 10.1097/00001665-200411000-00038. PMID: 15547407
Taylor PM
J Foot Surg 1976 Summer;15(2):55-8. PMID: 1030721

Clinical prediction guides

Serttas MF, Saglam F, Kochai A, Cakir A, Kantarci F, Dervişoğlu S
JBJS Case Connect 2023 Jul 1;13(3) Epub 2023 Sep 8 doi: 10.2106/JBJS.CC.23.00307. PMID: 37683077
Farrell K, Comis LE, Casimir MM, Hodsdon B, Jiménez-Silva R, Dunigan T, Bhattacharyya T, Jha S
PM R 2023 May;15(5):587-595. Epub 2022 May 30 doi: 10.1002/pmrj.12817. PMID: 35403375Free PMC Article
De Ridder R, Boudin E, Zillikens MC, Ibrahim J, van der Eerden BCJ, Van Hul W, Mortier G
Bone 2020 Aug;137:115406. Epub 2020 May 7 doi: 10.1016/j.bone.2020.115406. PMID: 32387835
Gnoli M, Staals EL, Campanacci L, Bedeschi MF, Faletra F, Gallone S, Gaudio A, Mattina T, Gurrieri F, Percesepe A, Neri I, Virdi A, Tremosini M, Milanesi A, Brizola E, Pedrini E, Sangiorgi L
Calcif Tissue Int 2019 Aug;105(2):215-221. Epub 2019 May 25 doi: 10.1007/s00223-019-00565-6. PMID: 31129707
Reznik M, Fried GW
Arch Phys Med Rehabil 2005 Jul;86(7):1495-7. doi: 10.1016/j.apmr.2004.09.022. PMID: 16003689

Recent systematic reviews

Alsufyani NA, Aldosary RM, Alrasheed RS, Alsaif RF
Acta Odontol Scand 2021 Mar;79(2):124-131. Epub 2020 Jul 30 doi: 10.1080/00016357.2020.1797160. PMID: 32730731
Faruqi T, Dhawan N, Bahl J, Gupta V, Vohra S, Tu K, Abdelmagid SM
Biomed Res Int 2014;2014:670842. Epub 2014 Oct 22 doi: 10.1155/2014/670842. PMID: 25530967Free PMC Article

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