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Semergen Mar 2018
Topics: Arm; Hand; Humans; Male; Middle Aged; Osteopoikilosis; Radiography
PubMed: 28579321
DOI: 10.1016/j.semerg.2017.04.008 -
Bone Aug 2017Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal...
Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic findings of MEL occur in OPK. However, germline mutation of LEMD3 does not explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy with polyostotic MEL and characteristic overlying scleroderma-like skin, a few bony lesions consistent with OPK, and a large epidermal nevus known to usually harbor a HRAS, FGFR3, or PIK3CA gene mutation. Exome sequencing was performed to ~100× average read depth for his two dermatoses, two areas of normal skin, and peripheral blood leukocytes. As expected for non-malignant tissues, the patient's mutation burden in his normal skin and leukocytes was low. He, his mother, and his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair deletion in LEMD3. Radiographs of the patient and his mother revealed bony foci consistent with OPK, but she showed no MEL. For the patient, somatic variant analysis, using four algorithms to compare all 20 possible pairwise combinations of his five DNA samples, identified only one high-confidence mutation, heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both his dermatoses but absent in his normal skin and blood. Thus, sparing our patient biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his scleroderma-like dermatosis considered a surrogate for MEL. This implicates postzygotic mosaicism of mutated KRAS, perhaps facilitated by germline LEMD3 haploinsufficiency, causing his MEL.
Topics: Adolescent; Exome; Genetic Predisposition to Disease; Humans; Male; Melorheostosis; Mosaicism; Mutation; Nevus; Osteopoikilosis; Osteosclerosis; Proto-Oncogene Proteins p21(ras)
PubMed: 28434888
DOI: 10.1016/j.bone.2017.04.010 -
American Journal of Medical Genetics.... Jul 2017The 12q14 microdeletion syndrome is a rare condition characterized by low birth weight, failure to thrive, short stature, learning disabilities, and osteopoikilosis. To...
The 12q14 microdeletion syndrome is a rare condition characterized by low birth weight, failure to thrive, short stature, learning disabilities, and osteopoikilosis. To date, 20 cases of 12q14 deletion have been reported in the literature, displaying both phenotypic than genetic variability. We report on three familial cases, a mother and two brothers, with severe short stature. The mother and elder brother presented with osteopoikilosis while the younger brother had severe short stature and developmental delay. SNP array analysis revealed a 1.9 Mb heterozygous 12q14.2q14.3 deletion in all three patients encompassing 14 genes and 3 miRNAs. In addition, the younger brother carried a paternal 11q13.4 duplication including the SHANK2 gene. This latter patient was investigated for developmental delay and did not show osteopoikilosis, confirming the role of age in the clinical presentation of this condition. To the best of our knowledge, this is the second family described with the syndrome. Comparing the clinical and molecular data of our patients with those previously reported we performed a detailed genotype-phenotype correlation confirming the association between growth retardation and osteopoikilosis when the rearrangement includes both LEMD3 and HMGA2 genes. In addition, we suggest the XPOT, TBK1, WIF1 genes as candidates for the clinical features observed in our patients and discuss for the first time the possible involvement of some microRNAs, when deleted, in the etiology of the phenotypes in 12q14 microdeletion syndrome patients. We expect the interpretation of our findings to be useful both from a molecular point of view and for genetic counseling.
PubMed: 28407409
DOI: 10.1002/ajmg.a.38253 -
Anais Brasileiros de Dermatologia 2016Elastoma is a connective tissue nevus characterized by changes in elastic fibers. It can be congenital or acquired, and is usually diagnosed before puberty. Associated...
Elastoma is a connective tissue nevus characterized by changes in elastic fibers. It can be congenital or acquired, and is usually diagnosed before puberty. Associated with osteopoikilosis, it is known as Buschke-Ollendorff syndrome. Histopathology with specific staining for elastic fibers is critical for a diagnostic conclusion. This report describes the case of a 7-year-old male patient with lesions diagnosed as elastoma, with absence of bone changes in the radiological imaging. This study aims to report the clinical presentation and histological examination of such unusual disease.
Topics: Biopsy; Child; Dermis; Diagnosis, Differential; Elastic Tissue; Humans; Male; Nevus; Osteopoikilosis; Rare Diseases; Skin Diseases, Genetic
PubMed: 28300889
DOI: 10.1590/abd1806-4841.20164541 -
Der Radiologe Apr 2017Increasing numbers of conventional X‑rays, computed tomography and magnetic resonance imaging in the inpatient, outpatient and scientific routine leads to an... (Review)
Review
BACKGROUND
Increasing numbers of conventional X‑rays, computed tomography and magnetic resonance imaging in the inpatient, outpatient and scientific routine leads to an increasing number of incidental findings. The correct interpretation of these incidental findings with respect to the relevance and the evaluation concerning further work-up is an important task of radiologists.
OBJECTIVE
Description of common incidental findings in musculoskeletal imaging and their clinical classification.
MATERIAL AND METHODS
A PubMed literature search was performed using the following terms: incidental findings, population-based imaging, musculoskeletal imaging, non-ossifying fibroma, enchondroma, osteodystrophia deformans, chondrosarcoma, fibrous dysplasia, simple bone cyst, unicameral bone cyst, solitary bone cyst, aneurysmal bone cyst, vertebral hemangioma, bone island, osteopoikilosis, Tarlov cyst and diffuse idiopathic skeletal hyperostosis (DISH).
RESULTS
Incidental findings are observed in up to 40% of imaging procedures. In up to 6% these incidental findings involve the skeletal system. Common incidental findings are discussed and their clinical relevance is explained.
Topics: Bone Cysts, Aneurysmal; Humans; Incidental Findings; Magnetic Resonance Imaging; Musculoskeletal Diseases; Musculoskeletal System; Radiography; Tomography, X-Ray Computed
PubMed: 28289785
DOI: 10.1007/s00117-017-0231-1 -
Nuklearmedizin. Nuclear Medicine Dec 2016
Topics: Aged; Diagnosis, Differential; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Humans; Male; Oligopeptides; Osteopoikilosis; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Spinal Neoplasms
PubMed: 27922151
DOI: No ID Found -
Internal Medicine (Tokyo, Japan) 2016
PubMed: 27725561
DOI: 10.2169/internalmedicine.55.7161 -
Skeletal Radiology Nov 2016To describe the bone imaging features of lipodystrophies in the largest cohort ever published.
OBJECTIVE
To describe the bone imaging features of lipodystrophies in the largest cohort ever published.
MATERIALS AND METHODS
We retrospectively examined bone imaging data in 24 patients with lipodystrophic syndromes. Twenty-two had genetic lipodystrophy: 12/22 familial partial lipodystrophy (FPLD) and 10/22 congenital generalized lipodystrophy (CGL), 8 with AGPAT2-linked CGL1 and 2 with seipin-linked CGL2. Two patients had acquired generalized lipodystrophy (AGL) in a context of non-specific autoimmune disorders. Skeletal radiographs were available for all patients, with radiographic follow-up for two. Four patients with CGL1 underwent MRI, and two of them also underwent CT.
RESULTS
Patients with FPLD showed non-specific degenerative radiographic abnormalities. Conversely, CGL patients showed three types of specific radiographic alterations: diffuse osteosclerosis (in 7 patients, 6 with CGL1 and 1 with CGL2), well-defined osteolytic lesions sparing the axial skeleton (7 CGL1 and 1 CGL2), and pseudo-osteopoikilosis (4 CGL1). Pseudo-osteopoikilosis was the sole bone abnormality observed in one of the two patients with AGL. Osteolytic lesions showed homogeneous low signal intensity (SI) on T1-weighted and high SI on T2-weighted MR images. Most of them were asymptomatic, although one osteolytic lesion resulted in a spontaneous knee fracture and secondary osteoarthritis in a patient with CGL1. MRI also showed diffuse fatty bone marrow alterations in patients with CGL1, with intermediate T1 and high T2 SI, notably in radiographically normal areas.
CONCLUSIONS
The three types of peculiar imaging bone abnormalities observed in generalized lipodystrophic syndromes (diffuse osteosclerosis, lytic lesions and/or pseudo-osteopoikilosis) may help clinicians with an early diagnosis in pauci-symptomatic patients.
Topics: Acyltransferases; Adolescent; Adult; Aged; Bone and Bones; Child; Child, Preschool; Chorionic Gonadotropin; Diagnosis, Differential; Female; Genetic Predisposition to Disease; Humans; Lipodystrophy, Congenital Generalized; Male; Middle Aged; Osteosclerosis; Syndrome; Young Adult
PubMed: 27631079
DOI: 10.1007/s00256-016-2457-9 -
Zhongguo Gu Shang = China Journal of... Jun 2016To analyze the imaging features of osteopoikilosis and its diagnosis knowledge.
OBJECTIVE
To analyze the imaging features of osteopoikilosis and its diagnosis knowledge.
METHODS
The imaging data of 9 patients with osteopoikilosis were analyzed retrospectively, including 6 familial cases and 3 sporadic cases. In 6 familial cases,there were 4 males and 2 females with an average age of 28 years old ranging from 10 to 63 years. Clinical manifestations of 1 familial case were left knee pain and limitation of activity for 3 years, and other 5 cases without clinical manifestation. In 3 sporadic cases, there were 2 males and 1 female with an average age of 33.7 years old ranging from 25 to 44 years. Three sporadic cases had obvious injury history with following up from 6 to 12 months. All imaging results of 9 cases were observed.
RESULTS
The imaging data of 6 familial osteopoikilosis showed the multiple round or oval nodes within bone with clear margins, uniform density, different size. The occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and carpus and tarus. X-ray features of 3 sporadic osteopoikilosis were similar to that of 6 familial cases and for 6 to 12 months follow-up X-ray features were unchanged.
CONCLUSION
The imaging features of osteopoikilosis are relatively specific such as the multiple mottling dense focal within bone with clear border and bilateral symmetry, and the focus located on cancellous bone and the diaphyses usually is unaffected. The imaging is a valuable examination for the accurate diagnosis of osteopoikilosis.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Osteopoikilosis; Pedigree; Radiography; Young Adult
PubMed: 27534091
DOI: No ID Found -
Case Reports in Dermatological Medicine 2016Introduction. Buschke-Ollendorf syndrome (BOS) is an uncommon syndrome characterized by osteopoikilosis and other bone abnormalities, accompanied by skin lesions, most...
Introduction. Buschke-Ollendorf syndrome (BOS) is an uncommon syndrome characterized by osteopoikilosis and other bone abnormalities, accompanied by skin lesions, most frequently connective tissue nevi. BOS is caused by mutations in the LEMD3 gene, which encodes the inner nuclear membrane protein Man1. We describe a unique case of osteopoikilosis associated with late-onset localized scleroderma and familial LEMD3 mutations. Case Report. A 72-year-old woman presented with adult-onset diffuse morphea and bullous skin lesions. Evaluation revealed multiple hyperostotic lesions (osteopoikilosis) suggestive of BOS. DNA sequencing identified a previously undescribed nonsense mutation (Trp621X) in the LEMD3 gene encoding Man1. Two additional family members were found to have osteopoikilosis and carry the same LEMD3 mutation. Conclusions and Relevance. We report a unique familial LEMD3 mutation in an individual with osteopoikilosis and late-onset morphea. We propose that this constellation represents a novel syndromic variant of BOS.
PubMed: 27382493
DOI: 10.1155/2016/2483041