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Buschke-Ollendorff syndrome

Catherine McCuaig, MD
Barbara Miedzybrodzki, MD
Section Editor
Jennifer L Hand, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Buschke-Ollendorff syndrome (BOS) (MIM #166700) is a rare, inherited autosomal-dominant disorder with high penetrance and variable expressivity characterized by the presence of sclerotic bone lesions (osteopoikilosis, "spotted bones") and, rarely, melorheostosis in association with connective tissue nevi (CTN, elastomas and collagenomas) [1,2]. Most patients present both CTN and bone lesions, but some have only skin or skeletal lesions. Both skin and skeletal lesions are usually asymptomatic and in most cases discovered incidentally.


First described in 1928 by Buschke and Ollendorff as dermatofibrosis lenticularis disseminata, the disease has been reported under a variety of names, including dermatofibrosis lenticularis disseminata with osteopoikilosis, dermatofibrosis disseminated with osteopoikilosis, dermato-osteopoikilosis, dermato-osteopoikilosis with melorheostosis (a dripping wax appearance along the outer bone), osteopathia condensans disseminata, and connective tissue nevus syndrome.


BOS is a rare condition. The precise incidence and prevalence are unknown, as both the cutaneous and bone lesions are usually asymptomatic and detected incidentally [2-4]. Males and females are equally affected. Both inherited and sporadic forms have been described [5].


BOS is an autosomal dominant disorder with high penetrance and variable expressivity caused by loss-of-function germline mutations in the LEM domain-containing protein 3 (LEMD3) gene (also called MAN1) on chromosome 12q14 [6]. More than 125 pathogenic mutations of the LEMD3 gene have been detected, the vast majority of which are point mutations [7]. There is a single report of BOS occurring in a family without an LEMD3 mutation [5].

LEMD3 encodes an inner nuclear membrane protein that antagonizes the bone morphogenic proteins (BMPs) and transforming growth factor (TGF)-beta signalling pathways through interactions with specific SMAD family proteins. Loss-of-function mutations in LEMD3 result in upregulation of the downstream targets in both of these pathways, leading to alteration of fibroblast function and increased bone formation. Fibroblasts in affected patients produce more tropoelastin and elastin via enhanced TGF-beta and BMP signaling, resulting in the characteristic cutaneous phenotype [8,9].

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Literature review current through: Nov 2017. | This topic last updated: Aug 25, 2016.
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