Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis

Abstract

Melorheostosis is an exceptionally rare sclerosing hyperostosis that typically affects the appendicular skeleton in a limited segmental fashion. It occasionally occurs on a background of another benign generalised sclerosing bone condition, known as osteopoikilosis caused by germline mutations in LEMD3, encoding the inner nuclear membrane protein MAN1, which modulates TGFβ/bone morphogenetic protein signalling. Recent studies of melorheostosis lesional tissue indicate that most cases arise from somatic MAP2K1 mutations although a small number may arise from other genes in related pathways, such as KRAS. Those cases associated with MAP2K1 mutations are more likely to have the classic "dripping candle wax" appearance on radiographs. The relationship between these somatic mutations and those found in a variety of malignant conditions is discussed. There are also similar germline mutations involved in a group of genetic disorders known as the RASopathies (including Noonan syndrome, Costello syndrome and various cardiofaciocutaneous syndromes), successful treatments for which could be applied to melorheostosis. The diagnosis and management of melorheostosis are discussed; there are 4 distinct radiographic patterns of melorheostosis and substantial overlap with mixed sclerosing bone dysplasia. Medical treatments include bisphosphonates, but definitive guidance on their use is lacking given the small number of patients that have been studied. Surgical intervention may be required for those with large bone growths, nerve entrapments, joint impingement syndromes or major limb deformities. Bone regrowth is uncommon after surgery, but recurrent contractures represent a major issue in those with extensive associated soft tissue involvement.

Osteopoikilie – ein posttraumatischer Zufallsbefund mit Literaturübersicht

“…plantare und einer Dakryozystitis (Günal-Seber-Başaran-Syndrom) auf [13]. Des Weiteren findet sich eine ätiologische Verwandtschaft zur Osteopathia striata [14] und zur Melorheostose [15,16], diese sind jedoch in der Regel in der radiologischen Bildgebung gut von der Osteopoikilie zu diskriminieren [17]. Im CT-Schnittbild kommen die Herdbefunde einer Osteopoikilie als hyperdense, noduläre Areale zur Darstellung [17].…”

A Rare Case of Melorheostosis in the Hand of a Saudi Woman

“…Melorheostosis is diagnosed through standard radiographs, which show a linear area of osteosclerosis along with the affected bones, producing a dripping candle wax appearance [5]. This case study presents a case of melorheostosis diagnosed and treated at King Faisal Specialist Hospital and Research Centre.…”

“…Patients commonly present with pain, deformities, limitations of a range of motion, contractures, muscle atrophy, and limb swelling [5]. Most cases were diagnosed incidentally and may involve different skeletal regions such as vertebrae, sternum, or upper and lower extremities, with the lower limbs being the most affected [1,[6][7].…”

Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study

“…(1) Patients commonly present with pain, deformities, limitations of range of motion, contractures, muscle atrophy, and limb swelling Fig 1. Most patients present in childhood or adolescence, with 50% patients being diagnosed by age 20 years. (2) Germline mutations in LEMD3 were identified in a patient with melorheostosis and osteopoikilosis. (3) However, the findings could not be replicated in patients with sporadic melorheostosis.…”