Osteopoikilosis and multiple exostoses caused by novel mutations in <Emphasis Type="Italic">LEMD3</Emphasis> and <Emphasis Type="Italic">EXT1</Emphasis> genes respectively - coincidence within one family

Background  

Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones 1]. Heterozygous LEMD3 gene mutations were shown to be the primary cause of the disease 2]. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) 3]. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones 4–6]. However, not all MRO affected individuals carry germ-line LEMD3 mutations 7]. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous LEMD3 mutation coincides with a novel mutation in EXT1, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both LEMD3 and EXT1 gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group.