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Nature Medicine Nov 2013Heterotopic ossification, the pathologic formation of extraskeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and...
Heterotopic ossification, the pathologic formation of extraskeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and lethal. However, the underlying molecular mechanisms are largely unknown. Here we demonstrate that Gαs restricts bone formation to the skeleton by inhibiting Hedgehog signaling in mesenchymal progenitor cells. In progressive osseous heteroplasia, a human disease caused by null mutations in GNAS, which encodes Gαs, Hedgehog signaling is upregulated in ectopic osteoblasts and progenitor cells. In animal models, we show that genetically-mediated ectopic Hedgehog signaling is sufficient to induce heterotopic ossification, whereas inhibition of this signaling pathway by genetic or pharmacological means strongly reduces the severity of this condition. As our previous work has shown that GNAS gain-of-function mutations upregulate WNT-β-catenin signaling in osteoblast progenitor cells, resulting in their defective differentiation and fibrous dysplasia, we identify Gαs as a key regulator of proper osteoblast differentiation through its maintenance of a balance between the Wnt-β-catenin and Hedgehog pathways. Also, given the results here of the pharmacological studies in our mouse model, we propose that Hedgehog inhibitors currently used in the clinic for other conditions, such as cancer, may possibly be repurposed for treating heterotopic ossification and other diseases caused by GNAS inactivation.
Topics: Animals; Bone Diseases, Metabolic; Cell Differentiation; Chromogranins; Female; GTP-Binding Protein alpha Subunits, Gs; Hedgehog Proteins; Humans; Male; Mice; Mice, Knockout; Mutation; Ossification, Heterotopic; Osteoblasts; Signal Transduction; Skin Diseases, Genetic; Wnt Signaling Pathway; beta Catenin
PubMed: 24076664
DOI: 10.1038/nm.3314 -
World Journal of Clinical Cases Feb 2020Pseudohypoparathyroidism type Ia (PHP Ia) is a rare hereditary syndrome, and patients with early PHP Ia are generally not diagnosed based on the presentation of...
BACKGROUND
Pseudohypoparathyroidism type Ia (PHP Ia) is a rare hereditary syndrome, and patients with early PHP Ia are generally not diagnosed based on the presentation of cutaneous nodules as the main clinical feature. Here, we describe a Chinese boy with PHP Ia in whom the main clinical feature was cutaneous nodules, and the patient exhibited a novel mutation.
CASE SUMMARY
A 5-year-old boy presented with a 5-year history of cutaneous nodules scattered over his entire body. The patient had a short stature, round face, short neck, and slightly flattened nose; he also had multiple hard papules and cutaneous nodules scattered over his entire body. The patient had a significantly elevated parathyroid hormone level. His serum calcium level was reduced, while his serum phosphorus level was increased and his serum thyroid-stimulating hormone level was elevated. Skin biopsy showed osteoma cutis in subcutaneous tissue. Sanger sequencing revealed a frameshift mutation, c.399delT (p.Ser133Argfs*2) in exon 5 of the gene. The patient was diagnosed with PHP Ia and subclinical hypothyroidism. He was given 1,25-dihydroxyvitamin D, calcium carbonate, and synthetic L-thyroxine. After 3 months of treatment, the patient's parathyroid hormone level decreased, and his serum calcium and serum phosphorus levels were normal. Moreover, his thyroid-stimulating hormone level decreased.
CONCLUSION
These findings can help dermatologists to diagnose PHP Ia in patients with cutaneous nodules as the main early clinical feature.
PubMed: 32110670
DOI: 10.12998/wjcc.v8.i3.587 -
Medical Journal, Armed Forces India Apr 1994A case of osteoma cutis in a woman of 48 years is reported. The primary cutaneous ossification has a unique congenital and noninvasive nature. The histological features...
A case of osteoma cutis in a woman of 48 years is reported. The primary cutaneous ossification has a unique congenital and noninvasive nature. The histological features of the lesion are illustrated.
PubMed: 28769194
DOI: 10.1016/S0377-1237(17)31025-0 -
BMC Ophthalmology Mar 2024An ocular osseous choristoma is a growth of mature, compact bone in the ocular or periocular soft tissue, and it is the rarest form of ocular choristoma, accounting for...
BACKGROUND
An ocular osseous choristoma is a growth of mature, compact bone in the ocular or periocular soft tissue, and it is the rarest form of ocular choristoma, accounting for only 1.7% of all epibulbar choristomas.
CASE PRESENTATION
Herein we present the case of a 20-month-old girl who was referred to the oculoplasty clinic with a progressively growing mass in the left lateral canthus. It had been present since birth without ocular involvement. Upon examination the mass was firm with a smooth surface, measured 9 × 6 × 3 mm, and exhibited no episcleral attachment or ocular involvement. An excisional biopsy was performed, and the histopathological findings were consistent with osseous choristoma of the left lateral canthus.
CONCLUSIONS
This report highlights the importance of considering osseous choristoma in the differential diagnosis of eyelid lesions, particularly those that have been present since birth. It also emphasizes the need for further studies investigating associations between osseous choristomas and ocular canthi.
Topics: Female; Humans; Infant; Choristoma; Lacrimal Apparatus; Eye Diseases; Eyelids; Bone and Bones
PubMed: 38549111
DOI: 10.1186/s12886-024-03403-y -
The Canadian Veterinary Journal = La... Apr 2006A 10-year-old, spayed female, obese golden retriever, presented for immune-mediated thrombocytopenia, was successfully managed with the administration of vincristine and...
A 10-year-old, spayed female, obese golden retriever, presented for immune-mediated thrombocytopenia, was successfully managed with the administration of vincristine and prednisone. However, 6 mo after discontinuing corticosteroid therapy because of suspected iatrogenic hyperglucocorticoidism, the patient was presented with multiple, firm, bilaterally symmetric, dermal masses composed histologically of differentiated cortical bone.
Topics: Adrenal Cortex Hormones; Animals; Bone Neoplasms; Dog Diseases; Dogs; Female; Neoplasms, Multiple Primary; Osteoma; Purpura, Thrombocytopenic, Idiopathic
PubMed: 16642875
DOI: No ID Found -
Bone Mar 2010Progressive osseous heteroplasia (POH) is a rare genetic disorder characterized by dermal ossification during infancy and progressive ossification into deep connective... (Comparative Study)
Comparative Study
Progressive osseous heteroplasia (POH) is a rare genetic disorder characterized by dermal ossification during infancy and progressive ossification into deep connective tissue during childhood. POH is at the severe end of a spectrum of GNAS-associated ossification disorders that include osteoma cutis and Albright Hereditary Osteodystrophy (AHO). Here we describe two girls who have different clinical presentations that reflect the variable expression of GNAS-associated disorders of cutaneous ossification. Each girl had a novel heterozygous inactivating mutation in the GNAS gene. One girl had POH limited to the left arm with severe contractures and growth retardation resulting from progressive heterotopic ossification in the deep connective tissues. The other girl had AHO with widespread, superficial heterotopic ossification but with little functional impairment. While there is presently no treatment or prevention for GNAS-associated ossification disorders, early diagnosis is important for genetic counselling and for prevention of iatrogenic harm.
Topics: Adolescent; Child; Chromogranins; Female; GTP-Binding Protein alpha Subunits, Gs; Gene Silencing; Humans; Mutation; Ossification, Heterotopic; Skin
PubMed: 19900597
DOI: 10.1016/j.bone.2009.11.001 -
Cureus Feb 2020Cutaneous tender tumors manifest as painful dermal or subcutaneous masses. Acronyms, a memory aid created from the initial letters of other words, can be used to assist...
Foreign Body (Solder) and Reaction to the Foreign Body Presenting As a Cutaneous Tender Tumor: Case Report and a New Acronym to Aid in Recalling the Differential Diagnosis of Painful Skin Lesions.
Cutaneous tender tumors manifest as painful dermal or subcutaneous masses. Acronyms, a memory aid created from the initial letters of other words, can be used to assist in recalling a list of conditions. We report the case of a man who presented with a painful lesion on his leg; 15 years earlier, hot solder had embedded beneath his skin at that location. The subcutaneous mass was removed, and his symptoms resolved. Microscopic evaluation of the specimen showed a foreign body reaction to metal. Therefore, after correlating his medical history, clinical presentation, and pathology findings, the diagnosis of a foreign body (solder) and a foreign body reaction to solder, as a cause of the patient's painful skin lesion, was established. Including our patient's diagnosis for his painful skin lesion, the list of conditions that have been described as presenting as a cutaneous tender tumor include calcinosis cutis, angioendotheliomatosis, leiomyoma, metastases, hidradenoma, osteoma cutis, glomus tumor, scar, fibromyxoma, leiomyosarcoma, eccrine angiomatous hamartoma, Dercum's disease, piezogenic pedal papule, eccrine spiradenoma, neurilemmoma, something else (such as foreign body (solder) and a reaction to the foreign body), angiolipoma, neuroma, dermatofibroma, granular cell tumor, endometriosis, thrombus, blue rubber bleb nevus, angioma, chondrodermatitis nodularis helicis, and keloid. We introduce a novel acronym for painful lesions of the skin that was inspired by the book Charlotte's Web in which a barn spider (Charlotte), by weaving praises of a pig (Wilbur) into her web, is responsible for the pig's life being spared. Wilbur is a calm pig; however, there was an episode when he temporarily fled his pen and was subsequently induced, with a pail of slop, to get back into the pen. The new acronym for cutaneous tender tumors uses the initial letter of each of the 26 currently established painful skin lesions: CALM HOGS FLED PENS AND GET BACK.
PubMed: 32190505
DOI: 10.7759/cureus.6955 -
Annals of Dermatology Oct 2011Becker's nevus is a relatively common acquired focal epidermal melanotic hypermelanosis usually found in the region of the shoulder girdle of young men. Various skeletal...
Becker's nevus is a relatively common acquired focal epidermal melanotic hypermelanosis usually found in the region of the shoulder girdle of young men. Various skeletal malformations and cutaneous dermatoses have been reported in Becker's nevus. Osteoma cutis is a rare disorder characterized by compact bone formation in the dermis or subcutaneous tissue. Secondary ossification on nevi has been reported, but not with Becker's nevus. Herein, we report a case of Becker's nevus with accompanying osteoma cutis in an 18-year-old female.
PubMed: 22148062
DOI: 10.5021/ad.2011.23.S2.S247 -
Journal of the American Veterinary... Sep 2009
Topics: Animals; Female; Osteoma; Skin Neoplasms; Turtles
PubMed: 19719438
DOI: 10.2460/javma.235.5.511 -
BMC Musculoskeletal Disorders Mar 2023Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the...
BACKGROUND
Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the paternal GNAS gene. Herein, we report a case of POH caused by a novel mutation in exon 2 of the GNAS gene.
CASE PRESENTATION
A 5-year-old Chinese boy was referred to our hospital for a growing mass in his right foot. Although laboratory findings were normal, radiographic imaging revealed severe ossification in his right foot and smaller areas of intramuscular ossification in his arms and legs. A de novo mutation (c.175C > T, p.Q59X) in exon 2 of the GNAS gene was identified, prompting a diagnosis of POH. We conducted a systematic literature review to better understand this rare disease.
CONCLUSION
We have discovered that a de novo nonsense mutation in exon 2 of GNAS can lead to POH. Our literature review revealed that ankylosis of the extremities is the primary clinical outcome in patients with POH. Unlike other conditions such as fibrodysplasia ossificans progressiva (FOP), patients with POH do not experience respiratory failure. However, much remains to be learned about the relationship between the type of GNAS gene mutation and the resulting POH symptoms. Further research is needed to understand this complex and rare disease. This case adds to our current understanding of POH and will contribute to future studies and treatments.
Topics: Male; Humans; Child, Preschool; GTP-Binding Protein alpha Subunits, Gs; Rare Diseases; Ossification, Heterotopic; Myositis Ossificans; Exons; Mutation; Chromogranins
PubMed: 37003989
DOI: 10.1186/s12891-023-06371-4