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BMC Endocrine Disorders Mar 2022The GNAS gene on chromosome 20q13.3, encodes the alpha-subunit of the stimulatory G protein, which is expressed in most tissues and regulated through reciprocal genomic...
BACKGROUND
The GNAS gene on chromosome 20q13.3, encodes the alpha-subunit of the stimulatory G protein, which is expressed in most tissues and regulated through reciprocal genomic imprinting. Disorders of GNAS inactivation produce several different clinical phenotypes including pseudohypoparathyroidism (PHP), pseudopseudohypoparathyroidism (PPHP), progressive osseous heteroplasia (POH), and osteoma cutis (OC). The clinical and biochemical characteristics overlap of PHP subtypes and other related disorders presents challenges for differential diagnosis.
METHODS
We enrolled a total of 11 Chinese children with PHP in our study and analyzed their clinical characteristics, laboratory results, and genetic mutations.
RESULTS
Among these 11 patients, nine of them (9/11) presented with resistance to parathyroid hormone (PTH); and nine (9/11) presented with an Albright's hereditary osteodystrophy (AHO) phenotype. GNAS abnormalities were detected in all 11 patients, including nine cases with GNAS gene variations and two cases with GNAS methylation defects. These GNAS variations included an intronic mutation (c.212 + 3_212 + 6delAAGT), three missense mutations (c.314C > T, c.308 T > C, c.1123G > T), two deletion mutations (c.565_568delGACT*2, c.74delA), and two splicing mutations (c.721 + 1G > A, c.432 + 1G > A). Three of these mutations, namely, c.314C > T, c.1123G > T, and c.721 + 1G > A, were found to be novel. This data was then used to assign a GNAS subtype to each of these patients with six cases diagnosed as PHP1a, two cases as PHP1b, one as PPHP, and two as POH.
CONCLUSIONS
Evaluating patients with PTH resistance and AHO phenotype improved the genetic diagnosis of GNAS mutations significantly. In addition, our results suggest that when GNAS gene sequencing is negative, GNAS methylation study should be performed. Early genetic detection is required for the differential diagnosis of GNAS disorders and is critical to the clinician's ability to distinguish between heterotopic ossification in the POH and AHO phenotype.
Topics: Adolescent; Bone Diseases, Metabolic; Child; Child, Preschool; China; Chromogranins; Female; GTP-Binding Protein alpha Subunits, Gs; Humans; Infant; Male; Ossification, Heterotopic; Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism; Skin Diseases, Genetic
PubMed: 35296306
DOI: 10.1186/s12902-022-00941-8 -
Cureus Sep 2023Background In this study, we aimed to determine the prevalence and radiographic features of incidental head and neck soft tissue calcifications (STCs) on panoramic...
Background In this study, we aimed to determine the prevalence and radiographic features of incidental head and neck soft tissue calcifications (STCs) on panoramic imagesand assess their clinical significance. Methodology Following well-established training and calibration procedures, 9,553 digital panoramic radiographs (DPRs) taken between January 1, 2021, and January 31, 22, were retrospectively evaluated. Only obvious calcifications and clear differential diagnoses were considered. The presence, type, side (i.e., unilateral or bilateral), number (single or multiple), and the presence of different calcifications in the same individual were recorded. STCs were recorded according to age and gender. Data were analyzed using the chi-square test and Fisher's exact test using SPSS version 18.0 (IBM Corp., Armonk, NY, USA). Results Overall, 35.8% of the DPRs studied showed the presence of STCs, including ossified stylohyoid complex (OSHC) (10.3%), thyroid cartilage (9.8%), tonsillolith (9.2%), atherosclerotic plaques (5.8%), calcified triticeous cartilage (CTC) (5.1%), sialolith (1.9%), as well as intra-articular (1.3%) and other calcifications (0.1-0.8%), i.e., calcified lymph node, antrolith, rhinolith, phlebolith, and osteoma cutis. STCs were found to be more prevalent in middle-aged patients and in females. A significant relationship was identified between the presence of carotid artery calcification and calcified superior horn of thyroid cartilage (CSHTC), as well as between the presence of CSHTC and CTC. Calcifications were detected either bilaterally (n = 2,003) or unilaterally (n = 2,388); however, OSHC mostly showed bilateral calcifications (8.5%). Conclusions Panoramic radiographs of dental patients reveal the frequent occurrence of STCs in the head and neck region with differing radiographic features. Certain calcifications show gender and age differences. Accurate detection of STCs may guide the identification of potential underlying diseases and help initiate referral to the relevant multidisciplinary teams.
PubMed: 37766776
DOI: 10.7759/cureus.46025 -
Clinical and Experimental Dermatology Jun 2023
Topics: Humans; Scalp; Skin Diseases, Genetic; Ossification, Heterotopic; Alopecia; Skin Neoplasms
PubMed: 36897160
DOI: 10.1093/ced/llad087 -
Indian Journal of Dermatology,... 2017
Topics: Adult; Bone Diseases, Metabolic; Cutis Laxa; Female; Humans; Ossification, Heterotopic; Pseudoxanthoma Elasticum; Skin Diseases, Genetic
PubMed: 28540877
DOI: 10.4103/ijdvl.IJDVL_690_16 -
European Journal of Endocrinology Dec 2016Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), which... (Review)
Review
OBJECTIVE
Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), which encompasses rare, related and highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and the results of an in vitro assay to measure Gsa protein activity. However, this classification disregards other related diseases such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), as well as recent findings of clinical and genetic/epigenetic background of the different subtypes. Therefore, the EuroPHP network decided to develop a new classification that encompasses all disorders with impairments in PTH and/or PTHrP cAMP-mediated pathway.
DESIGN AND METHODS
Extensive review of the literature was performed. Several meetings were organised to discuss about a new, more effective and accurate way to describe disorders caused by abnormalities of the PTH/PTHrP signalling pathway.
RESULTS AND CONCLUSIONS
After determining the major and minor criteria to be considered for the diagnosis of these disorders, we proposed to group them under the term 'inactivating PTH/PTHrP signalling disorder' (iPPSD). This terminology: (i) defines the common mechanism responsible for all diseases; (ii) does not require a confirmed genetic defect; (iii) avoids ambiguous terms like 'pseudo' and (iv) eliminates the clinical or molecular overlap between diseases. We believe that the use of this nomenclature and classification will facilitate the development of rationale and comprehensive international guidelines for the diagnosis and treatment of iPPSDs.
Topics: Bone Diseases, Metabolic; Dysostoses; Europe; Humans; Intellectual Disability; Ossification, Heterotopic; Osteochondrodysplasias; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Pseudohypoparathyroidism; Skin Diseases, Genetic
PubMed: 27401862
DOI: 10.1530/EJE-16-0107 -
Annals of Dermatology Nov 2023
PubMed: 38061755
DOI: 10.5021/ad.22.120 -
AJNR. American Journal of Neuroradiology Apr 2017Osteoma cutis of the face represents a primary or secondary formation of ossific foci in the facial skin. Its primary form has been sparsely described in the plastic...
BACKGROUND AND PURPOSE
Osteoma cutis of the face represents a primary or secondary formation of ossific foci in the facial skin. Its primary form has been sparsely described in the plastic surgery and dermatology literature. As radiologists, we routinely encounter incidental, very small facial calcified nodules on CT studies performed for a variety of unrelated reasons. We hypothesized that this routinely encountered facial calcification represents primary miliary osteoma cutis and is a common, benign, age-related finding.
MATERIALS AND METHODS
We retrospectively reviewed 1315 consecutive sinus CTs obtained during an 8-month period and their associated demographics. The number of dermal radiopaque lesions with Hounsfield units of >150 was counted, and we analyzed the association between the prevalence of these lesions and patients' demographics with logistic regression methods.
RESULTS
Five hundred ninety-nine males and 716 females from 4 to 90 years of age were included in the study (mean, 52 versus 51 years; = .259). Among these, 252 males and 301 females had small facial calcified nodules (42.1% versus 42.0%, = .971). The patient's age was a statistically significant predictor for having facial calcified nodules (odds ratio = 1.02, < .001), while the patient's sex was not ( = .826).
CONCLUSIONS
Facial calcified nodules, observed in routine head and face CT imaging, are common, benign, age-related findings, which have been largely overlooked in the radiology literature. It is a manifestation of primary miliary osteoma cutis.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Bone Diseases, Metabolic; Calcinosis; Child; Child, Preschool; Face; Facial Neoplasms; Female; Humans; Incidental Findings; Male; Middle Aged; Ossification, Heterotopic; Prevalence; Retrospective Studies; Sex Factors; Skin Diseases, Genetic; Tomography, X-Ray Computed; Young Adult
PubMed: 28232495
DOI: 10.3174/ajnr.A5096 -
Indian Dermatology Online Journal 2020Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive extraskeletal bone formation. POH is clinically suspected by cutaneous ossification,...
Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive extraskeletal bone formation. POH is clinically suspected by cutaneous ossification, usually presenting in early life, that involves subcutaneous and then subsequently deep connective tissues, including muscle and fascia. We report a case of POH in a 3-year-old child with multiple nontender subcutaneous nodules which, on radiology and histopathology, showed intracutaneous bone formation. Although there is no specific and effective treatment, knowledge about this entity is necessary for early detection and genetic counseling of parents.
PubMed: 32832452
DOI: 10.4103/idoj.IDOJ_502_19 -
Ophthalmic Plastic and Reconstructive... 2017Most bony and cartilaginous lesions of the orbit and periorbital compartments are benign, grow endophytically, and are composed of dense lamellar bone (eburnated or...
Most bony and cartilaginous lesions of the orbit and periorbital compartments are benign, grow endophytically, and are composed of dense lamellar bone (eburnated or ivory osteomas). An 87-year-old woman had a well-circumscribed, firm, round, and exophytic lesion of the brow region for at least 15 years. Excisional surgery disclosed an osteocartilaginous lesion with an enveloping pseudocapsule (periosteum/perichondrium) and a narrow stalk connecting it to the frontal bone. The periphery of the lesion displayed lamellar bone which appeared to be replacing a central cartilaginous zone. The adjacent deep preaponeurotic fat displayed nodules of collagen with myxoid change and occasional CD34 spindle cells suggestive of a spindle cell lipoma. Because of the osteochondroma's deep location in the preaponeurotic fat, the lesion differs from an osteoma cutis found in the dermis which fails to exhibit a cartilaginous component or a periosteum. Other clinically simulating lesions are described.
Topics: Aged, 80 and over; Biopsy; Bone Neoplasms; Female; Humans; Orbit; Orbital Neoplasms; Osteochondroma
PubMed: 28614150
DOI: 10.1097/IOP.0000000000000943 -
Clinical, Cosmetic and Investigational... 2021Osteoma cutis (OC) is a group of rare skin ossification diseases, most of which are secondary to inflammation, scarring, trauma, or tumors, but a small portion are...
Osteoma cutis (OC) is a group of rare skin ossification diseases, most of which are secondary to inflammation, scarring, trauma, or tumors, but a small portion are primary. Plate-like osteoma cutis is rare, especially after puberty. This report documents a case of a 30-year-old female, who presented with multiple stone-hard plates on the forehead and bilateral temples, with no relevant family history, or abnormalities in metabolism. These lesions showed slow progression over the last 11 years. The pathological diagnosis confirmed osteoma cutis. The forehead lesions were treated surgically due to aesthetic problems. In addition, long-term follow-up and observations are still needed to determine progression to deeper levels of tissue.
PubMed: 34588790
DOI: 10.2147/CCID.S325501