-
Acta Dermatovenerologica Alpina,... Mar 2020Buschke-Ollendorff syndrome (BOS) is a rare genetic hereditary genodermatosis characterized by benign skeletal and cutaneous lesions. Skeletal alterations known as...
Buschke-Ollendorff syndrome (BOS) is a rare genetic hereditary genodermatosis characterized by benign skeletal and cutaneous lesions. Skeletal alterations known as osteopoikilosis (OPK) or "spotted bone disease" are asymptomatic areas of sclerosing dysplasia. Two skin lesion patterns have been described because they may be of either elastic tissue (juvenile elastoma) or collagenous composition (dermatofibrosis lenticularis disseminata). We present the case of a 6-year-old male patient with yellowish papules that coalesced to form plaques localized on both thighs and on the upper limbs consistent with a connective tissue nevus (CTN) diagnosis. X-ray examination of the skeletal system revealed the presence of multiple small areas (measuring between 1 and 7 mm) of increased bone density (OPK) bilaterally. A skin biopsy was performed and did not show striking alterations in the number or dimension of the extracellular matrix fibers, but it showed mucin deposition between them, which is compatible with a CTN. This study reports on the clinical presentation and histological examination of this unusual disease.
Topics: Child; Humans; Male; Osteopoikilosis; Skin Diseases, Genetic
PubMed: 32206820
DOI: No ID Found -
Journal of Pediatric Genetics Mar 2020Buschke-Ollendorf Syndrome (BOS) is a benign autosomal dominant disorder caused by pathogenic mutations in . Here, we describe a family diagnosed to have varied...
Buschke-Ollendorf Syndrome (BOS) is a benign autosomal dominant disorder caused by pathogenic mutations in . Here, we describe a family diagnosed to have varied phenotypes associated with BOS. Single gene testing of detected a heterozygous frameshift pathogenic variant in both the affected family members. Besides the phenotypic description, this report highlights the need for a comprehensive evaluation in connective tissue disorders and the importance of genotype-phenotype correlation in BOS.
PubMed: 31976147
DOI: 10.1055/s-0039-1694767 -
BMC Research Notes Jun 2016We describe a male with functionally impairing radial deviation of the thumb who presented to us at 24 years of age. Two sclerotic skin lesions had been excised...
BACKGROUND
We describe a male with functionally impairing radial deviation of the thumb who presented to us at 24 years of age. Two sclerotic skin lesions had been excised 7 years before because of consecutive skin contracture. Latest radiological examination showed a spotted pattern consistent with osteopoikilosis.
CASE PRESENTATION
A corrective osteotomy of the thumb was carried out due to the patients discomfort. Facing the simultaneous osteo-cutaneous malformation we postulated a Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome is a rare autosomal-dominant hereditary disorder of connective tissue with typical osteo-cutaneous manifestations. To explore our hypothesis, biopsies were taken from the affected bone lesions and surrounding skin and soft tissue for histological investigation and genetic testing of the LEMD3 gene was performed on blood of the patient. The histology showed typical changes of the bone architecture and a fibrotic collagenous nodule of the skin. The genetic testing on DNA extracted from peripheral blood leucocytes confirmed a heterozygous loss of function mutation in the LEM domain-containing protein 3 (LEMD3) gene coding for the inner nuclear membrane protein MAN1, which causes osteopoikilosis by antagonizing transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signalling.
CONCLUSIONS
In atypical cases of simultaneous occurrence of fibrotic skin lesions and a spotted pattern in the X-ray we recommend the genetic screening of the LEMD3 gene. A correct diagnosis of Buschke-Ollendorff syndrome is necessary to spare patients from expensive investigations and to provide reassurance about the benign nature of the disease.
Topics: Abnormalities, Multiple; Base Sequence; DNA Mutational Analysis; DNA-Binding Proteins; Humans; Male; Membrane Proteins; Mutation; Nuclear Proteins; Osteopoikilosis; Sequence Homology, Nucleic Acid; Skin Abnormalities; Skin Diseases, Genetic; Thumb; Young Adult
PubMed: 27267960
DOI: 10.1186/s13104-016-2095-2 -
Annals of Laboratory Medicine Nov 2017Osteopoikilosis is an autosomal dominant bone disorder characterized by symmetric multiple osteosclerotic lesions throughout the axial and appendicular skeleton....
Osteopoikilosis is an autosomal dominant bone disorder characterized by symmetric multiple osteosclerotic lesions throughout the axial and appendicular skeleton. Pathogenic variants in the LEMD3 have been identified as the cause of osteopoikilosis. LEMD3 encodes an inner nuclear membrane protein that interacts with bone morphogenetic protein (BMP) and transforming growth factor (TGF)-β pathways. We report the case of a 19-year-old man presenting with lower back pain and sciatica. His radiograph revealed bilateral and symmetrical multiple osteosclerotic bone lesions in both scapular areas. Sanger sequencing of LEMD3 revealed a four-base-pair deletion in intron 2 (c.1560+5_1560+8del), [corrected] which was inherited from his father. We found that this four-base-pair deletion in intron 2 causes aberrant splicing and consequent deletion of exon 2. To the best of our knowledge, this is the first report of genetically confirmed osteopoikilosis in Korea.
Topics: Asian People; Bones of Lower Extremity; Bones of Upper Extremity; DNA Mutational Analysis; DNA-Binding Proteins; Exons; Humans; Introns; Male; Membrane Proteins; Nuclear Proteins; Osteopoikilosis; RNA Splice Sites; Republic of Korea; Sequence Deletion; Young Adult
PubMed: 28840995
DOI: 10.3343/alm.2017.37.6.540 -
Journal of Bone and Mineral Research :... Feb 2007Autosomal dominant OPK and BOS feature widespread foci of osteosclerotic trabeculae without or with skin lesions, respectively. Occasionally, a larger area of dense bone...
UNLABELLED
Autosomal dominant OPK and BOS feature widespread foci of osteosclerotic trabeculae without or with skin lesions, respectively. Occasionally, a larger area of dense bone in OPK or BOS resembles MEL, a sporadic sclerosing disorder primarily involving cortical bone. Others, finding deactivating germline LEMD3 mutations in OPK or BOS, concluded such defects explain all three conditions. We found germline LEMD3 mutations in OPK and BOS but not in sporadic MEL.
INTRODUCTION
In 2004, others discovered that heterozygous, loss-of-function, germline mutations in the LEMD3 gene (LEMD3 or MAN1) cause both osteopoikilosis (OPK) and Buschke-Ollendorff syndrome (BOS). OPK is an autosomal dominant, usually benign, skeletal dysplasia featuring multiple, small, especially metaphyseal, oval or round, dense trabecular foci distributed symmetrically throughout the skeleton. BOS combines OPK with connective tissue nevi comprised of collagen and elastin. In some OPK and BOS families, an individual may have relatively large, asymmetric areas of dense cortical bone interpreted as melorheostosis (MEL). MEL, however, classically refers to a sporadic, troublesome skeletal dysostosis featuring large, asymmetric, "flowing hyperostosis" of long bone cortices often with overlying, constricting soft tissue abnormalities. However, a heterozygous germline mutation in LEMD3 was offered to explain MEL.
MATERIALS AND METHODS
We studied 11 unrelated individuals with sclerosing bone disorders where LEMD3 mutation was a potential etiology: familial OPK (1), familial BOS (2), previously reported familial OPK with MEL (1), sporadic MEL (3), sporadic MEL with mixed-sclerosing-bone dystrophy (1), and patients with other unusual sclerosing bone disorders (3). All coding exons and adjacent mRNA splice sites for LEMD3 were amplified by PCR and sequenced using genomic DNA from leukocytes. We did not study lesional tissue from bone or skin.
RESULTS
In the OPK family, a heterozygous nonsense mutation (c.1433T>A, p.L478X) was discovered in exon 1. In the two BOS families, a heterozygous nonsense mutation (exon 1, c.1323C>A, p.Y441X) and a heterozygous frame-shift mutation (exon 1, c.332_333insTC) were identified. In the individual with MEL and familial OPK, a heterozygous nonsense mutation (c.1963C>T, p.R655X) was detected in exon 7. However, no LEMD3 mutation was found for any other patient, including all four with sporadic MEL.
CONCLUSIONS
We confirm that OPK and BOS individuals, including those with MEL-like lesions, have heterozygous, deactivating, germline LEMD3 mutations. However, MEL remains of unknown etiology.
Topics: Child; Female; Germ-Line Mutation; Humans; Male; Melorheostosis; Nevus; Osteopoikilosis; Syndrome
PubMed: 17087626
DOI: 10.1359/jbmr.061102 -
Proceedings of the Royal Society of... Apr 1950
Topics: Bone and Bones; Foot; Humans; Osteopoikilosis; Osteosclerosis
PubMed: 15417576
DOI: No ID Found -
Acta Reumatologica Portuguesa 2006Osteopoikilosis is a rare, benign and autosomal dominant bone disease. It is usually asymptomatic and diagnosed as a radiological finding. Plain X- Ray films show...
Osteopoikilosis is a rare, benign and autosomal dominant bone disease. It is usually asymptomatic and diagnosed as a radiological finding. Plain X- Ray films show multiple sclerotic lesions on periarticular areas, epiphyses and metaphyses of long tubular bones. The authors describe two cases of osteopoikilosis in subjects belonging to the same family (brothers).
Topics: Adult; Humans; Male; Osteopoikilosis; Radiography
PubMed: 17094337
DOI: No ID Found -
Journal of Orthopaedic Case Reports 2020Prostate cancer is one of the leading causes of death due to carcinoma in developed countries due to metastasis. Most of the patient at the time of diagnosis has shown...
INTRODUCTION
Prostate cancer is one of the leading causes of death due to carcinoma in developed countries due to metastasis. Most of the patient at the time of diagnosis has shown metastasis. Metastasis to bone leads to various skeletal-related events such as fracture and neural compression leading to increase morbidity in such patients. An early diagnosis leads to favorable outcomes. Skeletal metastasis is usually presented as osteoblastic localized lesion in the spine or pelvis. Here, we like to present a case of prostatic metastasis in a patient with widespread metastasis making the diagnosis in such condition a challenging issue.
CASE REPORT
A 61-year-old male comes with a complaint of right hip pain who has been diagnosed in some other clinic as a case of osteopoikilosis after an X-ray of the pelvis with both hips. However, on the further skeletal analysis found to involve most of the skeletal system with the diffuse osteolytic lesion. A bone scan, lab investigations helped in the arrival of diagnosis of atypical prostatic metastasis.
CONCLUSION
Prostate cancer is less likely to present as widespread osteolytic lesions. A very few case reports have been found in the literature regarding such presentation. This case demonstrates how to differentiate between metastasis and other common condition showing such presentation leading to an early diagnosis and thus improving the overall mortality and morbidity of the patients.
PubMed: 32953655
DOI: 10.13107/jocr.2020.v10.i02.1692 -
Proceedings of the Royal Society of... Feb 1953
Topics: Humans; Osteopoikilosis; Osteosclerosis
PubMed: 13037717
DOI: No ID Found -
Sultan Qaboos University Medical Journal Dec 2007
PubMed: 21748116
DOI: No ID Found