Osteopoikilosis With Germline LEMD3 Mutation Mimicking Bone Metastases in a Girl With a Concurrent Secreting Mixed Germ Cell Tumor.

Osteopoikilosis (OPK) is a rare, benign, asymptomatic bone disease causing dense bone lesions, which could be interpreted as bone metastasis. The symmetric distribution, lack of bone destruction, and location differentiate OPK from metastatic disease. It is essential to be aware of this benign condition to prevent diagnostic errors. We present the case of a 10-year-old female patient with the concurrent diagnosis of secreting mixed germ cell tumor with Yolk Salk Tumor compound and OPK. Physical examination disclosed an abdominal mass, and blood tests showed increased alfa-fetoprotein and human chorionic gonadotropin levels. Computed tomography revealed a pelvic tumor associated with multiple radiodense lesions distributed throughout the bone skeleton. Lesions were inactive on scintigraphy and FDG-PET. Pathology of the bone showed normal bone tissue and ruled out metastasis. The patient achieved complete remission after chemotherapy and surgery and remains in continued complete remission 28 months from diagnosis. The genetic analysis confirmed the LEMD3 germline mutation confirming OPK.

Depressed indurated plaque with elastorrhexis as a distinctive lesion in Buschke-Ollendorff syndrome.

Buschke-Ollendorff syndrome (BOS) is a rare autosomal dominant genodermatosis caused by heterozygous mutations in LEMD3 and characterized by connective tissue nevi and sclerotic bone lesions known as osteopoikilosis. We report a family with three individuals affected by BOS, two of whom manifested clinical and histopathological peculiarities, presenting with a depressed indurated plaque as the main cutaneous manifestation instead of the classic connective tissue nevi. Notable elastorrhexis was present in both biopsies.

Buschke-Ollendorff syndrome: a novel case series and systematic review.

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.

Ossifying fibroma in Buschke-Ollendorff syndrome.

Buschke-Ollendorff syndrome represents an autosomal dominant disorder characterized by connective tissue nevi and osteopoikilosis. Cutaneous lesions may contain either predominantly elastic fibers or predominantly collagen fibers or may show both connective tissue components. The disease results from mutations in LEMD3 (MAN1), which lead to enhanced transforming growth factor-ß (TGF-ß) signaling and resultant changes in fibroblast function. TGF-ß alterations have been implicated in a number of fibrotic disorders, and it is therefore not surprising that a range of cutaneous and skeletal abnormalities have been associated with Buschke-Ollendorff syndrome. Herein, we report a novel association between ossifying fibroma and Buschke-Ollendorff syndrome and discuss how these conditions are likely to be mechanistically linked.

Case report of a patient with osteopoikilosis.

Osteopoikilosis (OPK) is an uncommon osteosclerotic dysplasia. There is no exact evidence of its etiology and pathogenesis. Usually, it is an asymptomatic disease, and the diagnosis is made incidentally from radiographs, which show multiple, small, well-defined, variably shaped and widely distributed sclerotic areas over the skeleton. In this study, we report a 54-year-old man who suffers from back and leg pain and was diagnosed OPK by radiologically and review literature.

Coexistence of osteopoikilosis with seronegative spondyloarthritis and Raynaud's phenomenon: first case report with evaluation of the nailfold capillary bed and literature review.

Osteopoikilosis (OPK) is a rare autosomal dominant bone disorder characterized by numerous hyperostotic areas that tend to localize in periarticular osseous regions. It is usually asymptomatic and is often diagnosed incidentally during X-rays. OPK may be an isolated finding or associated with other pathologies, e.g. skin manifestations, rheumatic and/or skeletal disorders. We report a literature review and, for the first time, the coexistence of OPK with seronegative spondyloarthritis and Raynaud's phenomenon in a 48-year old female. To the best of our knowledge, this is the first case of OPK studied by videocapillaroscopy, demonstrating the absence of specific microvascular abnormalities of nailfold capillaries.

De Quervain's syndrome associated with osteopoikilosis: a case report and review of the literature.

Osteopoikilosis is a rare, usually asymptomatic, autosomal-dominant bone disorder, which is generally diagnosed incidentally on X-ray. De Quervain's syndrome is a disorder characterized by pain on the radial (thumb) side of the wrist, impairment of thumb function and thickening of the ligamentous structure covering the tendons in the first dorsal compartment of the wrist. In this case report, we present a young woman with De Quervain's syndrome associated with osteopoikilosis.

A rare benign disorder mimicking metastasis on radiographic examination: a case report of osteopoikilosis.

Osteopoikilosis (OPK) is a rare, autosomal dominant bone disorder, characterized by multiple, discrete round or ovoid radio densities scattered throughout the axial and appendicular skeleton. OPK is usually asymptomatic but rarely there may be slight articular pain and joint effusions. OPK is generally diagnosed incidentally on radiographic examinations and may mimic different bone pathologies, including bone metastases. Radionuclide bone scan has a critical role in distinguishing OPK from osteoblastic bone metastases. In this case report, we present a young man with right hip pain due to OPK, whose plain radiogram and computerized tomography findings thought cancer metastasis.

Osteopoikilosis and multiple exostoses caused by novel mutations in LEMD3 and EXT1 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 456. 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. METHODS: We investigated LEMD3 and EXT1 in the three-generation family from Poland, with 5 patients affected with osteopoikilosis and one child affected with multiple exostoses. RESULTS: We found a novel c.2203C > T (p.R735X) mutation in exon 9 of LEMD3, resulting in a premature stop codon at amino acid position 735. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 200 ethnically matched controls. Another new substitution G > A was found in EXT1 gene at position 1732 (cDNA) in Exon 9 (p.A578T) in three out of five osteopoikilosis affected family members. Evolutionary conservation of the affected amino acid suggested possible functional relevance, however no additional skeletal manifestations were observed other then those specific for osteopoikilosis. Finally in one member of the family we found a splice site mutation in the EXT1 gene intron 5 (IVS5-2 A > G) resulting in the deletion of 9 bp of cDNA encoding three evolutionarily conserved amino acid residues. This child patient suffered from a severe form of exostoses, thus a causal relationship can be postulated. CONCLUSIONS: We identified a new mutation in LEMD3 gene, accounting for the familial case of osteopoikilosis. In the same family we identified two novel EXT1 gene mutations. One of them A598T co-incided with the LEMD3 mutation. Co-incidence of LEMD3 and EXT1 gene mutations was not associated with a more severe skeletal phenotype in those patients.

A cause for concern? Osteopoikilosis found incidentally in the emergency department: a case report.

Osteopoikilosis is a rare, inherited bone disorder, which is usually found incidentally on x ray. It may be mistaken for other, more serious disorders such as bony metastases, causing undue distress to the doctor and patient.

Gastric cancer bone metastases together with osteopoikilosis diagnosed using bone scintigraphy and 18F-FDG PET/CT. / Coexistencia de metástasis óseas por cáncer gástrico y osteopoiquilia diagnosticadas mediante gammagrafía ósea y 18F-FDG PET/TC.

The coexistence of different bone diseases in the same patient involves a complex differential diagnosis. A patient is presented who was studied due to a renal mass that showed many sclerotic lesions in spine and limbs in conventional radiology and CT. These lesions were evaluated with 99mTC-HDP bone scintigraphy and 18F-FDG PET/CT, which helped to obtain the definitive pathological diagnosis of osteopoikilosis (OP) co-existing with gastric cancer bone metastases. Of the different imaging scans performed, bone scintigraphy was particularly relevant due to its ability to discriminate between benign and metastatic bone disease.

[A twelve-year-old teenager with bone pain and white papules]. / Douleurs osseuses et papules blanchâtres chez un adolescent de 12 ans.

Here we present a case report in which a teenager, with papules on the arm and back since the infancy, complained of back and right knee pain at the age of 12 years. The radiological examination led to the diagnosis of osteopoikilosis and melorheostosis. The Buschke-Ollendorff syndrome (BOS) associates osteopoikilosis (asymptomatic bone dysplasia) and disseminated dermatofibrosis. The BOS is rare, and its association with melorheostosis (another bone dysplasia in which pain and deformity may occur) makes the prognosis uncertain. This case report highlights the diagnosis problems related with bone pain in paediatrics. The purpose of this manuscript is to present the characteristics of two bone dysplasias: osteopoikilosis and melorheostosis, and to discuss the involvement of each one in the clinical picture of our patient.

Melorheostosis in a family with autosomal dominant osteopoikilosis.

We describe a 19-year-old woman with melorheostosis and osteopoikilosis (mixed sclerosing bone dysplasia). Her sister and mother had osteopoikilosis, but no evidence of melorheostosis. Isolated melorheostosis and melorheostosis with osteopoikilosis are sporadic disorders. Osteopoikilosis is an autosomal dominant trait. Mixed sclerosing bone dysplasia in a family with autosomal dominant osteopoikilosis raises the possibility that the two bone disorders may be related. This family and that of Butkus et al. [1997: Am J Med Genet 72:43-46] suggest that the melorheostosis could be due to a second mutation at the same locus as that which causes autosomal dominant osteopoikilosis.

Melorheostosis in a patient with familial osteopoikilosis.

We report on a 40-year-old woman with melorheostosis who also had radiographic findings of generalized osteopoikilosis. Three of her sibs have osteopoikilosis, but none of them have melorheostosis. Several cases of "mixed sclerosing bone dysplasia" have been described previously, and all have been sporadic. Isolated melorheostosis without osteopoikilosis is also generally a sporadic condition, but osteopoikilosis has been described as an autosomal-dominant trait. The finding of mixed sclerosing bone dysplasia in a family with osteopoikilosis suggests that the melorheostotic component of this disorder may be due to a second mutation at the same locus that causes isolated familial osteopoikilosis.

Mixed sclerosing bone dystrophy. Report of a case and review of the literature.

A 63-year old woman was admitted because of hip pain. Radiographs showed multiple round and oval sclerotic lesions involving humeral heads, pelvis, vertebral bodies and both femoral bones. Diaphyseal periosteal proliferation was found in metatarsal bones. A diagnosis of mixed sclerosing bone dystrophy was made. We review clinical, epidemiological and radiological findings of this entity.

Buschke-Ollendorff syndrome in a grande multipara: a case report and short review of the literature.

A 36-year-old short-statured grande multipara (gravida 10, para 8) with diabetes mellitus and hyperlipidaemia was incidentally found to have Buschke-Ollendorff syndrome (osteopoikilosis and dermatofibrosis lenticularis disseminata). The pelvis and hips, followed by the knees, were the sites mainly affected by the osteopoikilosis. The lumbosacral spine was also affected. She had a single connective tissue naevus on the right thigh. Apart from two abortions, the repeated pregnancies were uneventful and all her deliveries were normal at full-term or nearly full-term. With regard to the relationship between Buschke-Ollendorff syndrome and multiparity, it was apparent that multiparity did not affect the involved weight bearing bony structures, nor did the disseminated osteopoikilosis interfere with the endurance of multiple pregnancies. Buschke-Ollendorff syndrome is known generally to have a benign course, a feature that is illustrated in this case, even when associated with the stresses of multiparity. The report also provides a short and updated review of various clinical aspects of the syndrome and its associations, some of which are of a serious nature.

Coexistence of osteopoikilosis and discoid lupus erythematosus: a case report.

Osteopoikilosis is an uncommon, benign sclerosing bone dysplasia characterised by typical roentgenographic findings and usually seen in patients with dermatological problems. We report a case of osteopoikilosis and discoid lupus erythematosus presenting with skin and mucosal involvement, an association that has never previously been reported. We also discuss the differential diagnosis and the clinical pathologies accompanying osteopoikilosis in the literature.