Diseases title

Buschke-Ollendorff syndrome )

Lab mat 2
Orpha Number: 1306
Disseminated dermatofibrosis with osteopoikilosis

Buschke-Ollendorff syndrome (BOS) is a benign disorder characterized by the association of osteopoikilosis lesions (``spotted bones'') in the skeleton and connective tissue nevi in the skin. The exact prevalence is unknown but BOS is believed to affect around 1 in 20,000 individuals. Onset may occur at any age and expression of the bone and skin lesions is variable. Osteopoikilosis is characterized by small and round spots of increased bone density that are mainly located in the epiphyseal regions of the tubular bones. They are harmless and usually found by chance when radiographs are taken for other purposes, although pain and limited joint mobility have been reported in a minority of patients. The number of lesions can vary from a few to many lesions, usually found in the shoulders, elbows, wrists, pelvis, knees and ankles. The skin lesions encountered in the BOS are connective tissue nevi. These lesions can present as either widely disseminated, skin-colored to yellow small papules or as more localized larger lesions referred to as yellow plaques. In families with BOS, affected individuals can have both bone and skin lesions, or just one of these manifestations. Melorheostosis (see this term) has been described in some patients from BOS families. BOS is inherited in an autosomal dominant manner and is caused by heterozygous loss-of-function mutations in the LEMD3 gene (12q14). This gene codes for the inner nuclear membrane protein, LEMD3, which interacts with both the BMP and TGF-beta signaling pathways. Diagnosis of BOS is made by histological analysis of skin lesions and radiographic bone evaluation. Histologically, the skin lesions show a variable degree of connective tissue anomalies, mainly affecting the collagen and elastic fibers. The collagen bundles can be thickened and broad and the elastic fibers increased, irregular or fragmented but not calcified as is seen in pseudoxanthoma elasticum (see this term). The bone lesions can be scarce at a youngage and therefore be missed early in life. Ultrastructural examination of the bone lesions shows that they represent foci of numerous bone trabeculae that are slightly thicker than normal. These bone lesions should be differentiated from melorheostosis and sclerotic bone metastases. Osteopoikilosis also occurs as an isolated finding in individuals without a family history of BOS, as well as in association with other sclerosing dysplasias and as part of the 12q14 microdeletion syndrome (see these terms). As both the bone and skin lesions in BOS are generally asymptomatic, correct diagnosis is important to avoid unnecessary examinations and treatment. The prognosis for patients is good.
source: Orphanet