Buschke–Ollendorff Syndrome: A Novel Case Series and Systematic Review

V. Pope; L. Dupuis; P. Kannu; R. Mendoza-Londono; D. Sajic; J. So; G. Yoon; I. Lara-Corrales

Disclosures

The British Journal of Dermatology. 2016;174(4):723-729. 

In This Article

Abstract and Introduction

Abstract

Buschke–Ollendorff syndrome (BOS) is a rare, often benign, autosomal skin disorder. BOS commonly presents with nontender connective tissue naevi and sclerotic bony lesions (osteopoikilosis [OPK]). Herein, we summarize the presenting features of BOS and potential associations by conducting a systematic review of the literature and summarizing a cohort seen at the Hospital for Sick Children (HSC), Toronto, Canada. PubMed was searched using the following terms: 'BOS'; 'dermatofibrosis lenticularis'; 'OPK'; 'LEMD3'; 'elastoma'; 'collagenoma'. Only case reports were included, without date or language restrictions. Cases were further narrowed to those where patients or their families had a combination of skin and bony lesions, or a positive genetic test. Data were summarized using frequencies. In total, 594 reports were discovered, of which 546 (92%) were excluded. The remaining 48 accounted for 164 cases. Skin lesions were noted in 24% of cases and bony lesions in 20%, while 54% of patients had both. In 1% of cases the diagnosis was made on genetic testing alone. A family history was noted in 92% of cases. All patients with spinal stenosis (2%) or shortened status (7%) had OPK. Six per cent of patients had neurological problems. However, 50% of the cohort from HSC had cognitive delays, and only cases from 2007 onwards reported cognitive delays (the prevalence was 17% among those cases). This review confirms the classical diagnostic features of BOS. In addition, it highlights a previously unreported association between a shortened stature and OPK, as well as a possible association with cognitive delays.

Introduction

Buschke–Ollendorff syndrome (BOS) is a rare autosomal dominant genetic skin disorder with variable expression presenting as elastic or collagenous naevi, with or without several possible bony manifestations, especially osteopoikilosis (OPK). The skin manifestations were first described by Buschke and Ollendorff in 1928 as disseminated dermatofibrosis lenticularis.[1] BOS has an estimated incidence of 1 in 20 000 (0·0005%)[2] and is caused by loss-of-function mutations in LEMD3 (MIM 607844). The exact mechanism by which LEMD3 causes lesions is not yet understood.[3,4] Skin lesions typically appear in childhood, followed by OPK during the pubescent years. The skin lesions may increase in size and number as the patient ages, and, with time, numerous lesions may coalesce into one or more large plaques. Alternatively, small lesions may resolve naturally with age. Of the possible bony manifestations, OPK is by far the most common. This symptom typically manifests as asymptomatic dense 'bony islands', which appear as bright spots on radiographs. Melorheostosis, another rare associated symptom, presents with a dripping wax appearance along the outer bone. Unlike OPK, these rare bony lesions can be quite painful and hinder growth. The lower back, buttocks and legs are most affected by skin lesions, while the ends of long bones, hands and feet are most commonly affected by OPK. The head and neck area is almost always unaffected. There are no treatments and no mitigating factors for BOS. The skin lesions are generally small and asymptomatic, so intervention is often not required. However, an awareness of the bone lesions is important to prevent misdiagnosis if radiographs are taken for an unrelated reason.

The paucity of case reports complicates a full understanding of the disorder and its course. For this reason, we conducted a study reviewing all available literature on BOS, in order to better understand the symptoms, progression and associations of this disease. In addition, six previously unreported cases seen at the Hospital for Sick Children in Toronto were included with the literature.

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