Buschke-Ollendorff Syndrome: Sparing Unnecessary Investigations

Comment

In 1928, Buschke and Ollendorff¹ first reported the association between osteopoikilosis and dermatofibrosis lenticularis disseminata, which showed autosomal-dominant inheritance. Skin and bone lesions can occur independently in different family members. Two different clinical cutaneous patterns are described in BOS.^2-4 The first and most frequent form is characterized by yellowish nodules often grouped in plaques that are asymmetrically distributed, such as those seen in patient 1. The second form is known as dermatofibrosis lenticularis disseminata, which was seen in patient 2. Histologically, most lesions show normal collagen fibrils and an increased number of elastic fibers.

Osteopoikilosis, also known as spotted bone disease or osteopathia condensans, is a rare asymptomatic bone dysplasia of unknown etiology. It is characterized by an abnormality in the bone maturation process and often is found incidentally on radiologic examination, as seen in patient 1. Radiologic signs of osteopoikilosis consist of small, disseminated, well-circumscribed areas of increased radiodensity located in the epiphyses and metaphyses of long bones, as well as the pelvis, hands, and feet. These lesions, which typically are asymptomatic, could sometimes be associated with bone and/or joint pain but do not cause a predisposition to fractures. Documentation of these bone lesions by early adult life is important to avoid confusion with osteoblastic metastases on the skeleton.⁶

Buschke-Ollendorff syndrome is characterized by a variable expression. Loss-of-function mutations of the LEMD3 gene have been described in association with this disorder.⁷ This gene encodes an inner nuclear protein membrane with a C-terminal domain that binds SMAD2 and SMAD3 and antagonizes the bone morphogenetic proteins and transforming growth factor b. These proteins are involved in connective tissue morphogenesis, inducing elastin production from fibroblasts.⁷ Seven novel loss-of-function mutations of LEMD3 have been identified.⁸ The segmental manifestation of BOS could be a consequence of the mosaicism resulting from a somatic mutation.^9,10 A case describing the absence of LEMD3 mutation in an affected family suggested the genetic heterogeneity of BOS.¹¹

Conclusion

Buschke-Ollendorff syndrome is a benign condition with no repercussions on the patient’s health or quality of life. It does not require any specific treatment because the lesions generally remain asymptomatic and do not generate any substantial cosmetic burden. Mutation analysis was not performed in our patients because BOS has a good prognosis and the parents refused further investigation in both patients; therefore, a correct diagnosis was essential in our cases to rule out malignant bone disease in patient 1 whose osteopoikilosis prompted the workup and other disorders (eg, tuberous sclerosis, pseudoxanthoma elasticum) in patient 2 whose cutaneous lesions were the primary cause for presentation. A correct diagnosis of BOS is necessary to spare patients from expensive investigations and to provide reassurance about the benign nature of the disease.