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Journal of Cranio-maxillo-facial... Nov 2018Osteopetrosis is a rare condition which presents increased bone density and deficient bone remodeling. The consequential complications include cranial nerve impairment...
Osteopetrosis is a rare condition which presents increased bone density and deficient bone remodeling. The consequential complications include cranial nerve impairment due compression, bone fractures, and osteomyelitis. Maxillary osteomyelitis is uncommon even in osteopetrosis patients. This is a systematic review of the literature regarding the management and outcomes of maxillary osteomyelitis in patients with autosomal dominant osteopetrosis (ADO) type II. A case of this specific pathology is reported. There are 18 cases of maxillary osteomyelitis associated with ADO type II reported in the literature. The mean age of the patients reported was 33.5 (SD 15.9) years, and the male:female ratio was 1:1. Antibiotic therapy was variable, and amoxicillin with clavulanic acid was the main choice (33.33%). Surgery or sequestrectomy was performed in 88.89% of the studies. Complete healing was achieved in only 44.4% of cases. The treatment protocols remain controversial and often do not lead to complete healing. In the case that we report, complete healing was achieved after prolonged antibiotic therapy, hyperbaric oxygen therapy, and partial resection. In conclusion, the management of maxillary osteomyelitis in ADO type II patients is challenging, and complete resolution of the process is dependent on multiple interventions.
Topics: Humans; Maxillary Diseases; Osteomyelitis; Osteopetrosis
PubMed: 30309794
DOI: 10.1016/j.jcms.2018.09.004 -
Orphanet Journal of Rare Diseases Jun 2023CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain... (Review)
Review
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
Topics: Humans; Neuroglia; Leukoencephalopathies; Brain; Mutation; Nervous System Malformations; Atrophy
PubMed: 37349768
DOI: 10.1186/s13023-023-02772-9 -
Orphanet Journal of Rare Diseases Aug 2012Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs) in China. This study systematically... (Review)
Review
Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs) in China. This study systematically reviewed GSDs as defined in "Nosology and Classification of genetic skeletal disorders (2010 version)" using Chinese biomedical literature published over the past 34 years from 1978 to 2012. In total, 16,099 GSDs have been reported. The most frequently reported disorders were Marfan syndrome, osteogenesis imperfecta, fibrous dysplasia, mucopolysaccharidosis, multiple cartilaginous exostoses, neurofibromatosis type 1 (NF1), osteopetrosis, achondroplasia, enchondromatosis (Ollier), and osteopoikilosis, accounting for 76.5% (12,312 cases) of the total cases. Five groups (group 8, 12, 14, 18, 21) defined by "Nosology and Classification of genetic skeletal disorders" have not been reported in the Chinese biomedical literature. Gene mutation testing was performed in only a minor portion of the 16,099 cases of GSDs (187 cases, 1.16%). In total, 37 genes for 41 different GSDs were reported in Chinese biomedical literature, including 43 novel mutations. This review revealed a significant imbalance in rare disease identification in terms of geographic regions and hospital levels, suggesting the need to create a national multi-level network to meet the specific challenge of care for rare diseases in China.
Topics: Bone Diseases; China; Genetic Diseases, Inborn; Humans; Publishing
PubMed: 22913777
DOI: 10.1186/1750-1172-7-55 -
Bone Sep 2020To identify epigenetic and transcriptional factors controlling osteoclastogenesis (OCG), that have been shown to play a role in the pathogenesis of skeletal diseases.
OBJECTIVES
To identify epigenetic and transcriptional factors controlling osteoclastogenesis (OCG), that have been shown to play a role in the pathogenesis of skeletal diseases.
METHODS
A systematic review was conducted in accordance with the PRISMA guidelines. The PubMed and EMBASE databases were searched up to 30th April 2020; references of included articles and pertinent review articles were also screened to identify eligible studies. Studies were included if they described epigenetic and/or transcriptional regulation of OCG in a specific skeletal disorder, and quantified alterations in OCG by any well-described experimental method. Risk of bias was assessed by a previously described modification of the CAMARADES tool.
RESULTS
The combined searches yielded 2265 records. Out of these, 24 studies investigating 12 different skeletal disorders were included in the review. Osteoporosis, followed by osteopetrosis, was the most commonly evaluated disorder. A total of 22 different epigenetic and transcriptional regulators of OCG were identified; key epigenetic regulators included DNA methylation, histone methylation, histone acetylation, miRNAs and lncRNAs. In majority of the disorders, dysregulated OCG was noted to occur at the stage of formation of committed osteoclast from preosteoclast. Dysregulation the stage of formation of the preosteoclast from late monocyte was noted in rheumatoid arthritis and fracture, whereas dysregulation at stage of formation of late monocyte from early monocyte was noted in osteopetrosis and spondyloarthritis. Quality assessment revealed a high risk of bias in domains pertaining to randomization, allocation concealment, blinding of outcome assessors and determination of sample size.
CONCLUSIONS
A variety of epigenetic and transcriptional factors can result in dysregulated osteoclastogenesis in different skeletal disorders. Dysregulation can occur at any stage; however, the formation of committed osteoclasts from preosteoclasts is the most common target. Although the published literature on this subject seems promising, the overall strength of evidence is limited by the small number of studies evaluating individual skeletal disorders, and also by deficiencies in key aspects of study design.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Expression Regulation; Osteogenesis
PubMed: 32610074
DOI: 10.1016/j.bone.2020.115507 -
Clinical Genetics Sep 2023Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process.... (Meta-Analysis)
Meta-Analysis Review
Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process. Here we aimed to find the failure pattern of tooth eruption among five genetic diseases. Both systematic review and meta-analysis were used to identify the genotype-phenotype associations of unerupted teeth. The meta-analysis was based on the characteristics of abnormal tooth eruption in 223 patients with the mutations in PTH1R, RUNX2, COL1A1/2, CLCN7, and FAM20A respectively. We found all the patients presented selective failure of tooth eruption (SFTE). Primary failure of eruption patients with PTH1R mutations showed primary or isolated SFTE1 in the first and second molars (59.3% and 52% respectively). RUNX2 related cleidocranial dysplasia usually had SFTE2 in canines and premolars, while COL1A1/2 related osteogenesis imperfecta mostly caused SFTE3 in the maxillary second molars (22.9%). In CLCN7 related osteopetrosis, the second molars and mandibular first molars were the most affected. While FAM20A related enamel renal syndrome most caused SFTE5 in the second molars (86.2%) and maxillary canines. In conclusion, the SFTE was the common characteristics of most genetic diseases with abnormal isolated or syndromic tooth eruption. The selective pattern of unerupted teeth was gene-dependent. Here we recommend SFTE to classify those genetic unerupted teeth and guide for precise molecular diagnosis and treatment.
Topics: Humans; Tooth Eruption; Tooth, Unerupted; Core Binding Factor Alpha 1 Subunit; Tooth Abnormalities; Phenotype; Genotype; Chloride Channels
PubMed: 37448157
DOI: 10.1111/cge.14400 -
Pediatric Radiology Jan 2013Rickets is a complication of infantile osteopetrosis and pre-treatment recognition of this complication is important. (Review)
Review
BACKGROUND
Rickets is a complication of infantile osteopetrosis and pre-treatment recognition of this complication is important.
OBJECTIVE
To describe four children with infantile osteopetrosis complicated by rickets (osteopetrorickets) and review the relevant literature.
MATERIALS AND METHODS
Retrospective chart analysis of four infants with osteopetrorickets and a systematic review of the relevant literature.
RESULTS
We saw five children with infantile osteopetrosis, of whom four had superimposed rickets, for a period of 12 years. The review of the literature (including the current four children), yielded 20 children with infantile osteopetrorickets. The children ranged in age from 2 months to 12 months. In all children, hepatosplenomegaly was found. Sixteen (80%) children had visual impairments and eight (40%) children had hearing impairments. Serum calcium-phosphorus product was less than 30 in 18 children (90%). Twelve children (60%) were hypocalcemic and 18 (90%) were hypophosphatemic. In all children, the radiological examination demonstrated diffuse bony sclerosis and metaphyseal splaying and fraying of long bones. Five children (25%) had pathological fracture of extremities and 15 (75%) had rachitic rosary.
CONCLUSION
Rickets as a complication to infantile osteopetrosis is not uncommon. Skeletal roentgenograms are of critical importance in the diagnosis of both osteopetrosis and superimposed rickets.
Topics: Diagnosis, Differential; Female; Humans; Infant; Male; Osteoporosis; Radiography; Rickets
PubMed: 23151726
DOI: 10.1007/s00247-012-2511-2 -
JBMR Plus Jan 2018Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the... (Review)
Review
Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate-naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand-searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders (): osteogenesis imperfecta (), pycnodysostosis (), hypophosphatasia (), X-linked osteoporosis (), osteopetrosis, X-linked hypophosphatemia (), and osteoporosis pseudoglioma syndrome (). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate-naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted gene sequencing, an heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in . Targeted sequencing of , , , and genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs. A large multicenter collaborative study of well-phenotyped AFF cases and controls is needed to understand the role of genetics in this uncommon condition.
PubMed: 30283886
DOI: 10.1002/jbm4.10024 -
Frontiers in Endocrinology 2020Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive...
Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive radiographic imaging techniques and genetic analyses, bone biopsies are still valuable in the diagnosis of bone diseases. Advanced techniques for the assessment of bone quality in bone biopsies, which have emerged during the last decades, allows in-depth tissue analyses beyond structural changes visible in bone histology. In this review, we give an overview of the application and advantages of the advanced techniques for the analysis of bone biopsies in the clinical setting of various rare metabolic bone diseases. A systematic literature search on rare metabolic bone diseases and analyzing techniques of bone biopsies was performed in PubMed up to 2019 week 34. Advanced techniques for the analysis of bone biopsies were described for rare metabolic bone disorders including Paget's disease of bone, osteogenesis imperfecta, fibrous dysplasia, Fibrodysplasia ossificans progressiva, X-linked osteoporosis, Loeys-Diets syndrome, osteopetrosis, Erdheim-Chester disease, and Cherubism. A variety of advanced available analytical techniques were identified that may help to provide additional detail on cellular, structural, and compositional characteristics in rare bone diseases complementing classical histopathology. To date, these techniques have only been used in research and not in daily clinical practice. Clinical application of bone quality assessment techniques depends upon several aspects such as availability of the technique in hospitals, the existence of reference data, and a cooperative network of researchers and clinicians. The evaluation of rare metabolic bone disorders requires a repertoire of different methods, owing to their distinct bone tissue characteristics. The broader use of bone material obtained from biopsies could provide much more information about pathophysiology or treatment options and establish bone biopsies as a valuable tool in rare metabolic bone diseases.
Topics: Biopsy; Bone Diseases; Fibrous Dysplasia of Bone; Humans; Loeys-Dietz Syndrome; Myositis Ossificans; Osteitis Deformans; Osteogenesis Imperfecta; Osteopetrosis; Osteoporosis; Rare Diseases
PubMed: 32714279
DOI: 10.3389/fendo.2020.00399