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The Indian Journal of Radiology &... Apr 2014Melorheostosis is an uncommon mesenchymal dysplasia that rarely affects the axial skeleton. We describe two atypical cases of melorheostosis with classical imaging...
Melorheostosis is an uncommon mesenchymal dysplasia that rarely affects the axial skeleton. We describe two atypical cases of melorheostosis with classical imaging findings - the first one involving the cervico-dorsal spine with encroachment of left vertebral artery canal causing attenuation of the left vertebral artery and the second one of mixed sclerosing bony dysplasia (monomelic involvement coexisting with osteopoikilosis).
PubMed: 25024532
DOI: 10.4103/0971-3026.134415 -
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 -
Acta Radiologica Open Dec 2019Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome (BSCL), is a part of lipodystrophic syndromes that constitute a heterogeneous group of genetic...
Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome (BSCL), is a part of lipodystrophic syndromes that constitute a heterogeneous group of genetic or acquired generalized or partial body fat loss disorders. It is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. CGL is classified as type 1-4, depending on the gene involved, and bone lytic lesion is found frequently in type 1 especially in long bones, but reported to be rare in type 2. Here we report an active lifestyle 25-year-old woman with type 2 CGL showing multiple bone lytic and pseudo-osteopoikilosis lesions in hands and feet. Radiograph bone survey showed no apparent abnormality in pelvic bone or axial skeletons. Bone marrow was completely absent and extra-skeletal general fat loss was also evident in whole-body magnetic resonance imaging sparing the orbital, axial, sole, and palmar regions. Radiographic bone survey is important even for type 2 CGL to find the change of bones to provide direction of preventing excessive overload or activity.
PubMed: 31853371
DOI: 10.1177/2058460119892407 -
European Journal of Human Genetics :... May 2011We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and...
We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.
Topics: Abnormalities, Multiple; Adolescent; Body Height; Child; Child, Preschool; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 12; Dwarfism; Female; HMGA2 Protein; Humans; Male; Silver-Russell Syndrome; Syndrome
PubMed: 21267005
DOI: 10.1038/ejhg.2010.215 -
Journal of Medical Genetics Apr 2007This report presents the detection of a heterozygous deletion at chromosome 12q14 in three unrelated patients with a similar phenotype consisting of mild mental...
This report presents the detection of a heterozygous deletion at chromosome 12q14 in three unrelated patients with a similar phenotype consisting of mild mental retardation, failure to thrive in infancy, proportionate short stature and osteopoikilosis as the most characteristic features. In each case, this interstitial deletion was found using molecular karyotyping. The deletion occurred as a de novo event and varied between 3.44 and 6 megabases (Mb) in size with a 3.44 Mb common deleted region. The deleted interval was not flanked by low-copy repeats or segmental duplications. It contains 13 RefSeq genes, including LEMD3, which was previously shown to be the causal gene for osteopoikilosis. The observation of osteopoikilosis lesions should facilitate recognition of this new microdeletion syndrome among children with failure to thrive, short stature and learning disabilities.
Topics: Abnormalities, Multiple; Adult; Carrier Proteins; Chromosome Breakage; Chromosome Deletion; Chromosome Disorders; Chromosome Mapping; Chromosomes, Artificial, Bacterial; Chromosomes, Human, Pair 12; DNA-Binding Proteins; Dwarfism; Failure to Thrive; Female; HMGA2 Protein; Heterozygote; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Intellectual Disability; Learning Disabilities; Male; Membrane Proteins; Nerve Tissue Proteins; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Osteopoikilosis; Phenotype; Scoliosis; Sequence Deletion; Syndrome
PubMed: 17220210
DOI: 10.1136/jmg.2006.047860 -
Polish Archives of Internal Medicine Mar 2020
Topics: Adrenal Gland Neoplasms; Female; Humans; Low Back Pain; Middle Aged; Myelolipoma; Osteopoikilosis; Osteosclerosis
PubMed: 31976926
DOI: 10.20452/pamw.15158 -
Cureus Sep 2018Osteopoikilosis is a rare condition that is characterized by multiple small non-aggressive appearing sclerotic foci in a periarticular distribution. Typically, it does...
Osteopoikilosis is a rare condition that is characterized by multiple small non-aggressive appearing sclerotic foci in a periarticular distribution. Typically, it does not cause any symptoms and is diagnosed incidentally on imaging studies done for other reasons. We present a case of osteopoikilosis in a 37-year-old male, which was diagnosed incidentally on radiographs.
PubMed: 30430046
DOI: 10.7759/cureus.3253 -
Molecular Imaging and Radionuclide... Feb 2018Osteopoikilosis is an inherited condition with autosomal dominant trait resulting in sclerotic foci throughout the skeleton. It has been suggested that loss-of-function...
Osteopoikilosis is an inherited condition with autosomal dominant trait resulting in sclerotic foci throughout the skeleton. It has been suggested that loss-of-function mutations of LEMD3 gene located on 12q14.3 result in osetopoikilosis. A bp heterozygote deletion was detected in our patient at the cytosine nucleotide at position 1105 with molecular genetic analysis. Although this mutation has not been previously described, it was considered to be the most likely cause of the disease in our patient due to frame shift and premature stop codon formation. As in our case, three phase bone scintigraphy and whole body imaging did not reflect the true extent of lesion sites and lesion activity. SPECT/CT images could reflect lesion location and activity more accurately, and could be a good alternative for differential diagnosis of unexplained bone pain and sclerotic lesions in one examination.
PubMed: 29393055
DOI: 10.4274/mirt.25743 -
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 -
JAAD Case Reports Mar 2015
PubMed: 27051689
DOI: 10.1016/j.jdcr.2015.01.004