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Orphanet Journal of Rare Diseases Feb 2009Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density... (Review)
Review
Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs. The overall incidence of these conditions is difficult to estimate but autosomal recessive osteopetrosis (ARO) has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis (ADO) has an incidence of 1 in 20,000 births. Osteopetrotic conditions vary greatly in their presentation and severity, ranging from neonatal onset with life-threatening complications such as bone marrow failure (e.g. classic or "malignant" ARO), to the incidental finding of osteopetrosis on radiographs (e.g. osteopoikilosis). Classic ARO is characterised by fractures, short stature, compressive neuropathies, hypocalcaemia with attendant tetanic seizures, and life-threatening pancytopaenia. The presence of primary neurodegeneration, mental retardation, skin and immune system involvement, or renal tubular acidosis may point to rarer osteopetrosis variants, whereas onset of primarily skeletal manifestations such as fractures and osteomyelitis in late childhood or adolescence is typical of ADO. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X-linked traits with the most severe forms being autosomal recessive. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable, and paves the way to understanding natural history, specific treatment where available, counselling regarding recurrence risks, and prenatal diagnosis in severe forms. Treatment of osteopetrotic conditions is largely symptomatic, although haematopoietic stem cell transplantation is employed for the most severe forms associated with bone marrow failure and currently offers the best chance of longer-term survival in this group. The severe infantile forms of osteopetrosis are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal. It is anticipated that further understanding of the molecular pathogenesis of these conditions will reveal new targets for pharmacotherapy.
Topics: Adult; Bone Marrow Diseases; Child, Preschool; Fractures, Spontaneous; Genes, Dominant; Genes, Recessive; Humans; Infant, Newborn; Osteoclasts; Osteopetrosis; Prevalence
PubMed: 19232111
DOI: 10.1186/1750-1172-4-5 -
Acta Reumatologica Portuguesa 2009
Topics: Female; Humans; Osteopoikilosis; Radiography; Skin Diseases, Genetic; Young Adult
PubMed: 20852581
DOI: No ID Found -
Journal of Medical Case Reports Jul 2023Osteopoikilosis, also referred to as disseminated condensing osteopathy, spotted bone disease, or osteopecilia, is a rare bone disorder. The case presented here...
BACKGROUND
Osteopoikilosis, also referred to as disseminated condensing osteopathy, spotted bone disease, or osteopecilia, is a rare bone disorder. The case presented here showcases multiple disc lesions in the spine, extensive multifocal skin lesions, and positive test results for dermatomyositis and multifocal enthesopathy, accompanied by neurological symptoms. This manifestation represents a novel variant of the disease.
CASE PRESENTATION
Our patient is a 46-year-old mosque Kurdish servant presenting with complaints of pain in the right leg, lower back, right hand, and neck. Additionally, the patient has been experiencing redness in the right buttock and ipsilateral thigh, as well as gradually expanding and stiffening skin lesions on the left shin for the past 3 weeks. Painful neck movements and a positive Lasegue test were also observed in the right leg. The patient reports pain in the right buttock accompanied by a substantial erythematous area with induration measuring 8 × 15 cm, as well as an erythematous and maculopapular lesion measuring 6 × 18 cm on the left shin.
CONCLUSIONS
Our patient is a 46-year-old man presenting with complaints of skin lesions and pain in the lower back, pelvis, neck, and limbs. The X-ray reveals shoulder, pelvis, knee, and ankle involvement, while spinal involvement is observed in the neck and lumbar region. Furthermore, the bone scan indicates extensive enthesopathy in various regions, a unique manifestation not previously reported in similar cases.
Topics: Male; Humans; Middle Aged; Osteopoikilosis; Enthesopathy; Tomography, X-Ray Computed; Leg; Bone Diseases; Lumbosacral Region
PubMed: 37434212
DOI: 10.1186/s13256-023-04025-6 -
BMC Medical Genetics Jul 2010Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and...
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.
Topics: Adult; DNA-Binding Proteins; Exostoses, Multiple Hereditary; Female; Humans; Male; Membrane Proteins; Middle Aged; Mutation; N-Acetylglucosaminyltransferases; Nuclear Proteins; Osteopoikilosis; Pedigree
PubMed: 20618940
DOI: 10.1186/1471-2350-11-110 -
Medicina 2023
Topics: Humans; Osteopoikilosis; Incidental Findings; Radiography
PubMed: 38117729
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Oct 2020Bone islands (BI; enostoses) may be solitary or occur in the setting of osteopoikilosis (multiple bone islands) and are sometimes associated with Gardner's Syndrome... (Review)
Review
Bone islands (BI; enostoses) may be solitary or occur in the setting of osteopoikilosis (multiple bone islands) and are sometimes associated with Gardner's Syndrome (osteopoikilosis and colonic polyposis). Characteristic features of bone islands are (1) absence of pain or local tenderness, (2) typical radio dense central appearance with peripheral radiating spicules (rose thorn), (3) Mean CT (computerized tomography) attenuation values above 885 Hounsfield units (HU) (4) absence of uptake on bone scan and (5) radiographic stability over time. However, when enostoses display atypical features of pain, unusual radiographic appearance, aberrant HU, increased radiotracer uptake, and/or enlargement, they can be difficult to differentiate from more sinister bony lesions such as osteoblastic metastasis, low grade central osteosarcoma, osteoid osteoma and osteoblastoma. In this retrospective case series, the demographic, clinical, radiographic, treatment and outcome for ten patients with eleven atypical bone islands (ABI) are presented, some showing associated pain (5), some with atypical radiographic appearance (3), some with increased activity on BS (4), some with documented enlargement over time (7), one with abnormal CT attenuation value, some in the setting of osteopoikilosis (2), one in the setting of Gardner's Syndrome and one osteoid osteoma simulating a bone island. This series represents the spectrum of presentations of ABI. Comprehensive review of the literature reveals that the previous largest series of ABI showing enlargement as the atypical feature was in younger patients with jaw BI. Hence, this represents one of the largest series reported of ABI of all types in adults.
Topics: Adult; Bone Diseases; Bone Neoplasms; Humans; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 33065973
DOI: 10.3390/medicina56100534 -
Anales de Pediatria (Barcelona, Spain :... Dec 2014
Topics: Child; Child, Preschool; Female; Humans; Male; Osteopoikilosis; Skin Diseases, Genetic
PubMed: 24857429
DOI: 10.1016/j.anpedi.2014.03.001 -
Anales de Pediatria (Barcelona, Spain :... Oct 2014
Topics: Humans; Infant; Male; Osteopoikilosis; Skin Diseases, Genetic
PubMed: 24378571
DOI: 10.1016/j.anpedi.2013.11.008 -
International Journal of Paleopathology Jun 2021This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the... (Review)
Review
OBJECTIVE
This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the reasons for this.
MATERIALS
A 45-year bibliometric study of publications in seven bioarchaeological journals, along with two journals and editorial groups of broader scientific focus.
METHODS
Analyses of distribution patterns of the search hits and diachronic trends for achondroplasia, autosomal-dominant osteopetrosis, osteogenesis imperfecta, and osteopoikilosis, compared to those for tuberculosis as control measure of coverage.
RESULTS
Studies of ancient rare diseases (ARD) are mostly published as case reports in specialized journals and their number did not benefit from the introduction of biomolecular studies. The higher frequency of cases of achondroplasia suggests that not all rare diseases are equally under-represented.
CONCLUSIONS
Rare diseases are still largely under-represented in bioarchaeological literature. Their marginality likely results from a combination of taphonomic, methodological and public visibility factors.
SIGNIFICANCE
This article is the first attempt to provide a quantitative assessment of the under-representation of ARD and to outline the factors behind it.
LIMITATIONS
Rare diseases are an etiologically heterogeneous group. The number of surveyed journals and articles, as well as targeted diseases might be limiting factors.
SUGGESTIONS FOR FURTHER RESEARCH
Increasing collection and dissemination of data on ARD; opening a wide-ranging debate on their definition; implementation of biomolecular studies.
Topics: Bibliometrics; Humans; Paleopathology; Rare Diseases
PubMed: 33813348
DOI: 10.1016/j.ijpp.2021.03.003 -
The British Journal of Radiology Jun 2016There is a wide variety of hereditary and non-hereditary bone dysplasias, many with unique radiographic findings. Hereditary bony dysplasias include osteopoikilosis,... (Review)
Review
There is a wide variety of hereditary and non-hereditary bone dysplasias, many with unique radiographic findings. Hereditary bony dysplasias include osteopoikilosis, osteopathia striata, osteopetrosis, progressive diaphyseal dysplasia, hereditary multiple diaphyseal sclerosis and pyknodysostosis. Non-hereditary dysplasias include melorheostosis, intramedullary osteosclerosis and overlap syndromes. Although many of these dysplasias are uncommon, radiologists should be familiar with their genetic, clinical and imaging findings to allow for differentiation from acquired causes of bony sclerosis. We present an overview of hereditary and non-hereditary bony dysplasias with focus on the pathogenesis, clinical and radiographic findings of each disorder.
Topics: Bone Diseases, Developmental; Diagnosis, Differential; Evidence-Based Medicine; Genetic Predisposition to Disease; Humans; Osteosclerosis
PubMed: 26898950
DOI: 10.1259/bjr.20150349