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The estimated prevalence is of 1/1,100,000. More than 400 cases have been reported to date.

The disease usually presents in early childhood, and is frequently diagnosed before the age of 20, but can occur at any age. Patients can range from asymptomatic to those with joint contractures and/or chronic pain. The long bones of the extremities are most commonly affected and monostotic, polyostotic or monomelic presentations can occur. Usually, the initial manifestations are pain (from dull to sharp and penetrating), stiffness, limitation of joint movement or joint deformity. Pain is present in almost all cases and is usually aggravated by activity but it is rarely constant. Soft tissue fibrosis around the affected limb can also be noted. Other common associated manifestations include edema, hyperpigmented skin patches, circumscribed and linear scleroderma, vascular tumors and malformations. Limb shortening is rarely observed.

Etiology of melorheostosis is unknown and it is considered a sporadic disease probably due to somatic mosaicism for a genetic defect. The pathology is essentially that of abnormal proliferation of compact haversian bone distorting the contour of bone periosteal and endosteal surfaces.

Diagnosis is mainly based on conventional radiography. On plain radiographs, melorheostosis presents as linear lesions of increased bone density along the major axis (shafts or diaphyses) of the tubular bones. Lesions result in an increased thickness of the cortices and can expand to the external surface of the bones, giving the appearance of dripping wax along a candle. When there is polyostotic involvement, the linear lesions are typically continuous along the same side of the affected limb and ''jump'' across the joints. Soft tissue calcification and even ectopic ossification may be seen. Magnetic resonance imaging contributes to the assessment of soft tissue lesions. Radioisotope bone scanning can help distinguish melorheostosis from other bone lesions. Biopsy shows variable degrees of bone marrow fibrosis, along with markedly irregular bone with mixed areas of lamellar and woven bone. A mix of osteocartilagenous, fibrovascular, and adipose tissue is seen in the soft tissue masses.

The main differential diagnoses include bone tumors generating dense bone such as osteosarcoma, as well as osteopathia striata, osteopoikilosis, myositis ossificans progressiva (see these terms) and osteoma. Rarely, in families with osteopoikilosis or Buschke-Ollendorf syndrome, patients with melorheostosis may be present (as seen in melorheostosis with osteopoikilosis) (see these terms).

Melorheostosis is a sporadic disorder. There are no reports of parent to child transmission. For a parent with isolated melorheostosis, the risk of having an affected child is very low.

There is no curative treatment for melorheostosis. Management aims to relieve pain, correct deformity and restore movement of the affected limb(s). Bisphosphonates (pamidronate and etidronate) and most recently zoledronate have been shown to improve symptoms in some but not all patients (but further studies are needed). Physical therapy, serial casting, braces, manipulations, nerve blocks and sympathectomies are other conservative options. Surgical options include limb and tendon lengthening, fasciotomies, capsulotomies, osteotomies, excision of fibrous tissue and/or hyperostosis, contralateral epiphysiodesis, arthrodesis, callotasis and amputation. Surgical treatments are best performed after skeletal maturity is reached but deformities can recur.

Melorheostosis is not life-threatening but can greatly affect quality of life due to chronic pain that can worsen or reappear, even after surgery.