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Current Opinion in Pharmacology Jun 2018Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective... (Review)
Review
Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective tissues. There are common forms of HO that are triggered by extensive trauma, burns and other bodily insults, and there are also rare congenital severe forms of HO that occur in children with Fibrodysplasia Ossificans Progressiva or Progressive Osseous Heteroplasia. Given that HO is often preceded by inflammation, current treatments usually involve anti-inflammatory drugs alone or in combination with local irradiation, but are not very effective. Recent studies have provided novel insights into the pathogenesis of acquired and genetic forms of HO and have used the information to conceive and test new and more specific therapies in animal models. In this review, I provide salient examples of these exciting and promising advances that are undoubtedly paving the way toward resolution of this debilitating and at times fatal disease.
Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Bone Diseases, Metabolic; Bone and Bones; Drug Discovery; Genetic Predisposition to Disease; Humans; Molecular Targeted Therapy; Myositis Ossificans; Ossification, Heterotopic; Osteogenesis; Phenotype; Skin Diseases, Genetic
PubMed: 29614433
DOI: 10.1016/j.coph.2018.03.007 -
Cureus Aug 2018Osteoma cutis is the formation of bone within the skin. It can present as either primary osteoma cutis or secondary osteoma cutis. Secondary osteoma cutis is more common...
Osteoma cutis is the formation of bone within the skin. It can present as either primary osteoma cutis or secondary osteoma cutis. Secondary osteoma cutis is more common and is associated with inflammatory, infectious, and neoplastic disorders, including basal cell carcinoma. A 79-year-old Caucasian man without underlying kidney disease or calcium abnormalities presented with a basal cell carcinoma with osteoma cutis on the chin. Basal cell carcinoma with osteoma cutis has seldom been described; however, the occurrence of this phenomenon may be more common than suggested by the currently published literature. The preferred treatment is surgical excision-with or without using Mohs micrographic technique. When the histopathologic examination reveals bone formation in the skin, clinicians should consider the possible presence of an adjacent malignancy, such as a basal cell carcinoma.
PubMed: 30357056
DOI: 10.7759/cureus.3170 -
Human Mutation Jan 2015Pseudohypoparathyroidism type 1a (PHP1a) is characterized by hypocalcaemia and hyperphosphatemia due to parathyroid hormone resistance, in association with the features... (Review)
Review
Pseudohypoparathyroidism type 1a (PHP1a) is characterized by hypocalcaemia and hyperphosphatemia due to parathyroid hormone resistance, in association with the features of Albright's hereditary osteodystrophy (AHO). PHP1a is caused by maternally inherited inactivating mutations of Gs-alpha, which is encoded by a complex imprinted locus termed GNAS. Paternally inherited mutations can lead either to pseudopseudohypoparathyroidism (PPHP) characterized by AHO alone, or to progressive osseous heteroplasia (POH), characterized by severe heterotopic ossification. The clinical aspects and molecular genetics of PHP1a and its related disorders are reviewed together with the 343 kindreds with Gs-alpha germline mutations reported so far in the literature. These 343 (176 different) mutations are scattered throughout the 13 exons that encode Gs-alpha and consist of 44.9% frameshift, 28.0% missense, 14.0% nonsense, and 9.0% splice-site mutations, 3.2% in-frame deletions or insertions, and 0.9% whole or partial gene deletions. Frameshift and other highly disruptive mutations were more frequent in the reported 37 POH kindreds than in PHP1a/PPHP kindreds (97.3% vs. 68.7%, P < 0.0001). This mutation update and respective genotype-phenotype data may be of use for diagnostic and research purposes and contribute to a better understanding of these complex disorders.
Topics: Animals; Bone Diseases, Metabolic; Chromogranins; GTP-Binding Protein alpha Subunits, Gs; Genetic Association Studies; Genetic Predisposition to Disease; Genomic Imprinting; Humans; Mutation; Ossification, Heterotopic; Pseudohypoparathyroidism; Skin Diseases, Genetic
PubMed: 25219572
DOI: 10.1002/humu.22696 -
JAAD Case Reports Mar 2023
PubMed: 36873053
DOI: 10.1016/j.jdcr.2023.01.010 -
Endocrine Jun 2021Pseudohypoparathyroidism (PHP), the first known post-receptorial hormone resistance, derives from a partial deficiency of the α subunit of the stimulatory G protein... (Review)
Review
Pseudohypoparathyroidism (PHP), the first known post-receptorial hormone resistance, derives from a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key component of the PTH/PTHrP signaling pathway. Since its first description, different studies unveiled, beside the molecular basis for PHP, the existence of different subtypes and of diseases in differential diagnosis associated with genetic alterations in other genes of the PTH/PTHrP pathway. The clinical and molecular overlap among PHP subtypes and with different but related disorders make both differential diagnosis and genetic counseling challenging. Recently, a proposal to group all these conditions under the novel term "inactivating PTH/PTHrP signaling disorders (iPPSD)" was promoted and, soon afterwards, the first international consensus statement on the diagnosis and management of these disorders has been published. This review will focus on the major and minor features characterizing PHP/iPPSDs as a group and on the specificities as well as the overlap associated with the most frequent subtypes.
Topics: Bone Diseases, Metabolic; Dysostoses; Humans; Intellectual Disability; Ossification, Heterotopic; Osteochondrodysplasias; Parathyroid Hormone; Pseudohypoparathyroidism; Skin Diseases, Genetic
PubMed: 33179219
DOI: 10.1007/s12020-020-02533-9 -
Dermatology Online Journal Mar 2018Osteoma cutis, the development of bone in the dermis and/or subcutaneous fat, can occur as either a primary or secondary condition. Perforating osteoma cutis is rare. A...
Osteoma cutis, the development of bone in the dermis and/or subcutaneous fat, can occur as either a primary or secondary condition. Perforating osteoma cutis is rare. A man with a solitary lesion of perforating osteoma cutis is described and the features of individuals with a single perforating osteoma cutis skin lesion are reviewed. A solitary lesion of either primary or secondary perforating osteoma cutis has only been observed in two men and one woman; the lesions had been present from less than one month to 19 or 20 years prior to establishing the diagnosis. The lesion was either located on the forehead (two men) or the breast (one woman). The erythematous (two lesions) or flesh-colored nodules ranged in size from 8×8 millimeters to 1.5×0.5 centimeters. Each had epidermal perforation by bone through a central area that was either crateriform or crusted or keratotic. The clinical differential diagnosis included keratoacanthoma, phlebolith, pilomatricoma, pilomatrical carcinoma, and squamous cell carcinoma. The perforating osteoma cutis lesion was successfully treated with either excision or shave biopsy without recurrence at either 10 or 12-months follow-up.
Topics: Biopsy; Bone Diseases, Metabolic; Dermis; Diagnosis, Differential; Facial Neoplasms; Forehead; Humans; Male; Ossification, Heterotopic; Skin Diseases, Genetic
PubMed: 29634878
DOI: No ID Found -
Dermatology Online Journal Apr 2017We report a healthy, 44-year-old woman presenting with an at least a 20-year history of hardened papules in the forehead region, extending to the scalp. The biopsy and... (Review)
Review
We report a healthy, 44-year-old woman presenting with an at least a 20-year history of hardened papules in the forehead region, extending to the scalp. The biopsy and histopathologic exam confirmed a diagnosis of osteoma cutis. We review the literature review and discuss the classification of the cutaneous ossification process presented, along with the results of the surgical treatment.
Topics: Adult; Biopsy; Bone Diseases, Metabolic; Dermoscopy; Facial Dermatoses; Female; Forehead; Humans; Ossification, Heterotopic; Skin; Skin Diseases, Genetic
PubMed: 28541879
DOI: No ID Found -
Annals of Dermatology Nov 2023
PubMed: 38061755
DOI: 10.5021/ad.22.120 -
Journal of Cutaneous and Aesthetic... 2018Multiple miliary osteoma cutis is an uncommon condition presenting as multiple skin-colored papules of variable sizes on the face. A 48-year-old woman presented with...
Multiple miliary osteoma cutis is an uncommon condition presenting as multiple skin-colored papules of variable sizes on the face. A 48-year-old woman presented with multiple skin-colored hard papules on both cheeks. Examination revealed firm-to-hard dome-shaped asymptomatic papules in cluster over both cheeks. A punch biopsy was performed, which showed evidence of focal bony trabeculae with associated normal appendages. Few larger papules were incised and followed up with curettage of bony material and closed. All lesions could not be incised and removed because of large number of lesions in cluster.
PubMed: 30210214
DOI: 10.4103/JCAS.JCAS_54_17 -
Journal of the American Academy of... Sep 1991Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1)... (Review)
Review
Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8.
Topics: Bone Diseases; Bone and Bones; Humans; Radiography; Skin Diseases
PubMed: 1918486
DOI: 10.1016/0190-9622(91)70226-r