Melorheostosis (associated with osteopokilosis)

(OMIM phenotype number #155950)

Melorheostosis, also called "Leri disease", is a type of mixed sclerosing bone dysplasia, with alterations in both endochondral and intramembranous ossification. The radiographic findings are characterized by hardened wax that has dripped down the side of a candle. Dense, irregular and eccentric hyperostosis of both the cortex and the adjacent medullary canal of a single bone, or several adjacent bones have been described in this disorder. The bone lesions avidly accumulate radionuclide in a bone scan. The distribution of melorheostosis and its associated soft tissue lesions in sclerotomes, myotomes and dermatomes suggests a segmentary, embryogenetic defect. This may be an acquired defect related to spinal sensory nerves. Clinically, patients affected may have pain and stiffness of the involved bones, contractures when the osseous abnormality involves a joint, muscular atrophy and overlying skin changes. The skeletal lesions manifest in late childhood or early adulthood and progress during childhood and may or may not gradually extend in the adult years. Melorheostosis-like changes can be associated with osteopoikilosis. Less than 5 families have been reported in the literature to date. Osteopoikilosis is caused by a germline mutation in the LEMD3 gene (12q14), and a germline mutation in the LEMD3 gene may predispose individuals with osteopoikilosis to develop melorheostosis. However, the exact pathogenesis is currently unknown.

Differential diagnosis includes osteosarcoma in localised forms, myositis ossificans or calcified haematoma in cases associated with soft tissue calcifications. The therapeutic management is generally symptomatic, in case of severe deformity or contractures might be necessary surgery.

Gene

LEMD3 gene, 12q14.3 (OMIM gene/locus number #607844)

Phenotype

Joint contractures, contractures over affected bones, sclerodermatous skin lesions, skin atrophy over affected bones, sclerotic soft tissue over affected bones, muscle atrophy, hemangiomas, lymphedema, bone deformities with linear hyperostosis of the cortex of long bones reminiscent of dripping candle wax, flexion deformities over affected bones, flowing hyperostosis of bone cortex, osteosclerosis (lesions mainly affect diaphyses of long bones, hands, feet, and pelvis although epiphyses may also be affected).

Images

Fig. Radiograph shows: dense sclerosis involving the posterior cortex and adjacent medullary cavity of the proximal ulna with wavy margin. The elbow joint is not involved. The radius appeared normal.

Reproduced from J Chin Med Assoc, Vol 74, Abdullah S, Pang GM, Mohamed-Haflah NH, et al., Melorheostosis of the ulna., Pages 469-72, Copyright 2011, with permission from Elsevier.


References

  1. Jain VK, Arya RK, Bharadwaj M, et al. Melorheostosis: clinicopathological features, diagnosis, and management. Orthopedics. 2009 Jul;32(7):512.
  2. Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. 2004 Nov;36(11):1213-8.
  3. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  4. Ihde LL, Forrester DM, Gottsegen CJ, et al. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82.
  5. www.omim.org