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Craniofacial fibro-osseous lesions (CFOLs) are a diverse group of relatively rare entities whose etiology ranges from reactive to dysplastic with a potential for malignant transformation. It is distinguished by the replacement of bone with fibrous tissue, that subsequently develops different degrees of calcification. Fibrous dysplasia (FD) is a component of the fibro-osseous lesion spectrum. The clinical spectrum of FD is wide, ranging from minor monostotic lesions affecting a single bone to devastating polyostotic disease involving the entire skeleton. FD produces asymmetry, which impairs face aesthetics. FD leads to bone differentiation, disintegration, and disorganization. It depicts a cellular collagenous stroma lacking mitotic figures and pleomorphism. Blood capillaries are evenly distributed, as are elongated trabeculae of woven or lamellar bone with uneven curves (often referred to as the Chinese letters pattern). Three types of FD patterns can be identified by computed tomography (CT) imaging: a cystic pattern, a homogeneously dense pattern, and a ground-glass pattern. The cornerstone of treatment is surgery, although the method varies depending on the location, size, and symptoms of the lesion. As an alternative to surgery, the use of bisphosphonates to reduce osteoclastic activity is under consideration. In this case series, we present three cases of FD involving the maxilla and mandible. We aim to correlate the clinical presentation, histological features, and radiographic findings, to promote early diagnosis, treatment, and better prognosis of the patient.
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A total of 7% of all benign bone lesions are diagnosed as fibrous dysplasia (FD). The symptoms of FD of the jaw range from asymptomatic to dental anomalies, pain and facial asymmetry. Due to its resemblance to other fibro-osseous bone lesions, misdiagnosis often occurs and can lead to inadequate treatment. Particularly in the jaw, this lesion does not become quiescent during puberty, making fundamental knowledge about the diagnosis and treatment of FD crucial. Mutational analysis and nonsurgical approaches offer new diagnostic and therapeutic options. In this review, we examine the advances and the difficulties of the diagnosis and the various treatment modalities of FD of the jaw in order to capture the current scientific knowledge on this bone disease.
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Mazabraud's syndrome represents rare benign disorder characterized by simultaneous occurrence of fibrous dysplasia of bone and intramuscular myxomas within surrounding soft tissue. Mutations of GNAS1 gene were proven to be causative for this condition. Here, we present a case report of a patient with unusual manifestation of this disease, who developed a pathological fracture of the femur in the setting of monostotic fibrous dysplasia. The intramuscular myxoma of the thigh was discovered during the following orthopedic operation, where the intraoperative diagnosis became a pitfall of the case, as the intramuscular myxoma was initially diagnosed as a low-grade sarcoma from the frozen section. Apart from clinical findings, the diagnosis of Mazabraud's syndrome was further proven by histopathological evaluation and molecular studies of GNAS1 gene. This case raises awareness of such condition as it can easily become a diagnostic pitfall.
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Heterotopic ossification is defined as an aberrant formation of bone in extraskeletal soft tissue, for which both genetic and acquired conditions are known. This pathologic process may occur in many different sites such as the skin, subcutaneous tissue, skeletal muscle and fibrous tissue adjacent to joints, ligaments, walls of blood vessels, mesentery and other. The clinical spectrum of this disorder is wide: lesions may range from small foci of ossification to massive deposits of bone throughout the body, typical of the progressive genetically determined conditions such as fibrodysplasia ossificans progressiva, to mention one of the most severe and disabling forms. The ectopic bone formation may be regarded as a failed tissue repair process in response to a variety of triggers and evolving towards bone formation through a multistage differentiation program, with several steps common to different clinical presentations and distinctive features. In this review, we aim at providing a comprehensive view of the genetic and acquired heterotopic ossification disorders by detailing the clinical and molecular features underlying the different human conditions in comparison with the corresponding, currently available mouse models.
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Abstract Background Various studies demonstrating enhanced vulnerability to apoptosis may contribute to the pathobiology of schizophrenia. Objective Thus, G proteins may provide an intriguing link between the signal transduction, and apoptotic hypotheses of schizophrenia. In the light of these findings, we investigated whether G protein gene polymorphisms (GNAS1-T393C and GNB3-C825T) accounted for an increased risk of schizophrenia. Methods The present analyses were based on 100 subjects diagnosed with schizophrenia, and on 100 unrelated healthy controls. The genotyping of GNAS1-T393C, and GNB3-C825T gene polymorphisms were performed using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Results: We demonstrated the positive association of GNB3-C825T gene variants with schizophrenia risk (p: 0.023). In our study, more prevalent CC genotype frequencies were detected in GNB3 in patients compared with the frequencies in the controls. The individuals with GNB3-C825T CC genotype had 2 fold increased risk for schizophrenia (p: 0.011, c2: 6.39, OR:2.14, 95% CI: 1.18-3.90). Discussion Our study results suggested that GNB3-C825T polymorphism might be associated with schizophrenia.
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BACKGROUND: Certain constitutive chromosomal abnormalities of the human X chromosome are relatively common in conspicuous neuropsychiatric findings. Although tumors or tumor-like lesions are occasionally reported in diseases of the X chromosome, they are numerically negligible, for example, in aneuploidy such as the triple X syndrome (TXS). CASE REPORT: A 16-year-old female patient with a known TXS and premutation stage of fragile X syndrome was referred by her dentist for diagnosis and treatment of unilateral cheek swelling. The examination of the psychologically conspicuous patient revealed a unilateral mandibular tumor with dysesthesia of the mental nerve. Surgical removal of soft, crumbly spongiosa over the nerve canal resulted in sufficient pressure release of the constricted nerve and restoration of epicritic sensitivity. Imaging findings and histological and molecular genetic examination revealed monostotic craniofacial fibrous dysplasia. CONCLUSION: Although the data in the literature do not give reason to suppose an accumulation of neoplasms in TXS, a numb chin syndrome should be a reason for detailed diagnostics. Careful diagnosis allows for customized therapy. This is the first report on the coincidence of TXS, fragile X syndrome, and fibrous dysplasia in a single individual.
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Displasia Fibrosa Poliostótica/complicaciones , Síndrome del Cromosoma X Frágil/complicaciones , Enfermedades Mandibulares/complicaciones , Adolescente , Femenino , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Displasia Fibrosa Poliostótica/genética , Síndrome del Cromosoma X Frágil/psicología , Humanos , Enfermedades Mandibulares/diagnóstico por imagen , Enfermedades Mandibulares/genética , FenotipoRESUMEN
OBJECTIVE: Mazabraud's syndrome is a rare form of bone fibrous dysplasia associated with intramuscular myxomas. Fibrous dysplasia, is generally localized to pelvis and femur and it results in a fragile bone with deformities, pain, pathological fractures and functional impairment. Intramuscular myxomas, are rare benign mesenchymal neoplasms that exceptionally may evolve to malignant forms. METHODS: This case report describes a 66-year-old woman with Mazabraud's Syndrome (MS), characterized both by monostotic right femur fibrous dysplasia and by a solitary intramuscular myxoma at the right quadriceps muscle, that underwent a long-term treatment (4 years) with intravenous zoledronic acid. RESULTS: Zoledronic acid therapy rapidly lowered bone pain together with a reduction of intramuscular myxoma volume, but did not affect the extension of fibrous dysplasia. No adverse effects have been observed during treatment. CONCLUSION: Highly active bisphosphonates are commonly used for the treatment of bone metabolic disorders and they are generally well tolerated. Zoledronic acid may represent a promising alternative to surgical intervention in MS, although its use in rare form of bone fibrous dysplasias is still controversial.
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Displasia Fibrosa Ósea/diagnóstico , Neoplasias de los Músculos/diagnóstico , Mixoma/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Displasia Fibrosa Ósea/complicaciones , Displasia Fibrosa Ósea/patología , Humanos , Italia , Neoplasias de los Músculos/complicaciones , Neoplasias de los Músculos/patología , Mixoma/complicaciones , Mixoma/patología , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
Mazabraud's syndrome is a rare disorder characterised by the association of fibrous dysplasia with intramuscular myxomas. We present a 36-year-old woman with right anterior knee pain and a buttock mass. Imaging showed aggressive bone destruction within an area of fibrous dysplasia in the right femur and a mass with myxoid signal characteristics in the right adductor region. Biopsy of the femur revealed both fibrous dysplasia and a high-grade spindle cell sarcoma. Biopsy of the adductor mass confirmed a soft-tissue myxoma. Molecular genetic analysis revealed an identical R201H substitution in the GNAS1 gene in the sarcoma, the myxoma, and also the conventional fibrous dysplasia.
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Cromograninas/genética , Neoplasias Femorales/diagnóstico por imagen , Neoplasias Femorales/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mixoma/diagnóstico por imagen , Mixoma/genética , Sarcoma/diagnóstico por imagen , Sarcoma/genética , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/genética , Adulto , Biopsia , Nalgas/diagnóstico por imagen , Nalgas/patología , Nalgas/cirugía , Diagnóstico Diferencial , Femenino , Neoplasias Femorales/patología , Neoplasias Femorales/cirugía , Fémur , Humanos , Imagen por Resonancia Magnética , Mixoma/patología , Mixoma/cirugía , Clasificación del Tumor , Mutación Puntual , Sarcoma/patología , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
Fibrous dysplasia is a non-neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune-Albright syndrome, Jeffe-Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management.
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Displasia Fibrosa Craneofacial/genética , Enfermedades Maxilomandibulares/genética , Cromograninas/genética , Displasia Fibrosa Craneofacial/diagnóstico por imagen , Displasia Fibrosa Craneofacial/patología , Diagnóstico Diferencial , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Humanos , Enfermedades Maxilomandibulares/diagnóstico por imagen , Enfermedades Maxilomandibulares/patología , MutaciónRESUMEN
Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Neoplasias Hipofisarias/genética , Adenoma/genética , Mutación de Línea Germinal/genética , Adenoma Hipofisario Secretor de Hormona del Crecimiento/genética , Hipófisis/patología , Neoplasias Hipofisarias/patología , Brasil , ADN de Neoplasias , Marcadores Genéticos , Adenoma/patología , Transformación Celular Neoplásica , Estudios de Cohortes , Péptidos y Proteínas de Señalización Intracelular , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , CarcinogénesisRESUMEN
La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son caracteriÌsticos, aunque variables y de caraÌcter evolutivo. La gammagrafiÌa ósea es la teÌcnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnoÌstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)
Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Adulto Joven , Displasia Fibrosa Ósea/etiología , Displasia Fibrosa Ósea/tratamiento farmacológico , Osteogénesis/genética , Osteomalacia/complicaciones , Anomalías Congénitas , Vitamina D/uso terapéutico , Osteosarcoma/etiología , Calcio/uso terapéutico , Hipofosfatemia/sangre , Quistes Óseos Aneurismáticos/etiología , Diagnóstico Diferencial , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Fracturas Óseas/patología , Células Madre Mesenquimatosas/patología , Manejo del Dolor , Displasia Fibrosa Monostótica/etiología , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/sangre , Displasia Fibrosa Ósea/diagnóstico por imagen , Displasia Fibrosa Poliostótica/etiología , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Displasia Fibrosa Craneofacial/etiología , Mutación/genéticaRESUMEN
BACKGROUND: Aseptic loosening is a main cause for revision surgery after total hip arthroplasty (THA) and there is no reliable marker for the early detection of patients at high risk. This study has been performed to validate association of the T393C polymorphism (rs7121) in the GNAS1 gene, encoding for the alpha-subunit of heterotrimeric G-protein Gs, with risk for and time to aseptic loosening after THA, which has been demonstrated in our previous study. METHODS: 231 patients with primary THA and 234 patients suffering from aseptic loosening were genotyped for dependency on GNAS1 genotypes and analyzed. RESULTS: Genotyping revealed almost similar minor allele frequencies of 0.49 and 0.46, respectively. Consistently, genotype distributions of both groups were not significantly different (p = 0.572). Neither gender nor GNAS1 genotype showed a statistically significant association with time to loosening (p = 0.501 and p = 0.840). Stratification by gender, as performed in our previous study, was not able to show a significant genotype-dependent difference in time (female p = 0.313; male p = 0.584) as well as median time to aseptic loosening (female p = 0.353; male p = 0.868). CONCLUSION: This study was not able to confirm the results of our preliminary study. An association of the GNAS1 T393C polymorphisms with risk for and time to aseptic loosening after THA is unlikely.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Cromograninas/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Polimorfismo de Nucleótido Simple , Complicaciones Posoperatorias/genética , Falla de Prótesis , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación MissenseRESUMEN
Endogenous Cushing syndrome (CS) in pediatrics is rare; it may be caused by tumors that produce corticotropin in the pituitary gland or elsewhere, tumors that produce corticotropin-releasing hormone anywhere, and adrenocortical masses that produce cortisol. Adrenocortical cancer is a rare cause of CS in children but should be excluded first. CS in children is often caused by germline or somatic mutations with implications for patient prognosis and for their families. CS should be recognized early in children; otherwise, it can lead to significant morbidity and mortality. Patients with suspected CS should be referred to specialized clinical centers for workup.
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Síndrome de Cushing/diagnóstico , Síndrome de Cushing/genética , Neoplasias de la Corteza Suprarrenal/complicaciones , Hormona Adrenocorticotrópica , Niño , Hormona Liberadora de Corticotropina , Humanos , PediatríaRESUMEN
Odontogenic myxoma (OM) is a rare, benign, and locally aggressive tumor. It tends to occur in the posterior maxilla and mandible and is often associated with root resorption and perforation of cortex. Histopathologically, there is a proliferation of spindle, bipolar, and stellate cells, with bland nuclei within a myxoid to infrequently fibromyxoid extracellular matrix. Long, thin residual bony trabeculae are often seen floating within the spindle cell proliferation because of the infiltrating nature of this tumor, and these trabeculae impart a "soap bubble" or "tennis-racket" radiologic appearance. No syndromic association of OM has been reported. Although similar histopathologic features are shared with cardiac myxoma and soft tissue myxoma, mutations in the GNAS gene have not been identified in OM to date, and only 2 of 17 OMs showed mutations in the PRKAR1A gene. In this report, we describe a case of OM in a patient with constitutional 1q21 microduplication, a locus that harbors genes encoding certain proteins in the cAMP-dependent protein kinase A (PKA) signaling pathway, including G-protein-coupled receptors and 1 phosphodiesterase interacting protein. Review of the literature describes the key clinical features and molecular pathogenesis of 1q21 microduplication, as well as highlighting the role of PKA signaling pathway in the pathogenesis of myxomas in general.
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Duplicación Cromosómica , Cromosomas Humanos Par 1 , Mixoma/genética , Tumores Odontogénicos/genética , Adolescente , Biomarcadores de Tumor/genética , Biopsia , Cromograninas , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/genética , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Predisposición Genética a la Enfermedad , Humanos , Mutación , Mixoma/patología , Mixoma/cirugía , Tumores Odontogénicos/patología , Tumores Odontogénicos/cirugía , Fenotipo , Valor Predictivo de las Pruebas , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
Objective To investigate the clinical characteristics and molecular pathological mechanism of McCune-Albright syndrome ( MAS) in order to provide a guidance for the precision medicine of MAS. Method The clinical data and genetic findings of 41 patients with MAS were analyzed retrospectively. Results (1) MAS girls had the phenotype of peripheral precocious puberty with premature sexual development and high estradiol, low LH and FSH, and the increased volume of uterus and ovary. ( 2 ) In 41 MAS cases, there were 17 cases with GNAS1 gene mutation, and the total positive rate was 41. 5%, of which the classic triad was 66. 7%, two signs 56. 3%, and 12. 5% in only one classic sign. GNAS1 gene mutation was found in 78. 6% of patients with polyostotic fibrous dysplasia of bone, while only 55. 0% in patients with cafe au lait skin spots. Children with precocious puberty and fibrous dysplasia of bone is an important basis for clinical diagnosis of MAS, but cafe au lait skin spots does not seem to be the specifical manifestation of MAS. Conclusion Clinically MAS was lack of typical clinical manifestations, and the most important clinical weight factor for the diagnosis of MAS was peripheral precocious puberty with fibrous dysplasia of bone. GNAS1 gene screening may be helpful to improve the clinical accurate diagnosis of MAS.
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BACKGROUND: McCune-Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. CASE: A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization-induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. SUMMARY AND CONCLUSION: Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented.
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Displasia Fibrosa Poliostótica/complicaciones , Neoplasias Ováricas/complicaciones , Ovariectomía/métodos , Adulto , Diagnóstico Diferencial , Estrógenos/sangre , Femenino , Fertilidad , Displasia Fibrosa Poliostótica/cirugía , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Imagen por Resonancia Magnética , Quistes Ováricos/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Embarazo , Adulto JovenRESUMEN
Pseudohypoparathyroidism type 1A and its association with bipolar disorder (BD) have never been reported so far. We report a new case with both clinical entities and discuss the potential pathophysiological mechanisms of this association (protein kinase A hypoactivation, parathyroid hormone, hypocalcemia, protein kinase C activation, vitamin D deficiency). In this patient, the correction of the underlying calcium and vitamin D deficiencies leads to a better BD outcome and lower dosage of psychopharmacological agents. The conclusions might be generalized for a better understanding and management of these conditions.
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Trastorno Bipolar/complicaciones , Seudohipoparatiroidismo/complicaciones , Adulto , Comorbilidad , Femenino , Humanos , Seudohipoparatiroidismo/fisiopatología , Deficiencia de Vitamina D/complicacionesRESUMEN
Albright hereditary osteodystrophy (AHO) is a rare hereditary metabolic disorder that may or may not be associated with resistance to parathyroid hormone (pseudohypoparathyroidism) or other hormones. The disorder is commonly characterized by a constellation of dysmorphic physical features and with biochemical levels that demonstrate hypocalcaemia and hyperphosphatemia. We report here a clinical case of a 14 year old male with AHO and we discuss his clinical features, radiographic and laboratory findings along with treatment.
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Pseudohypoparathyroidism (PHP) is a group of genetic disorders in which the kidneys fail to respond to parathyroid hormone. Genetic defects in the GNAS complex locus lead to reduced Gsalpha (alpha-subunit of the heterotrimeric stimulatory G protein) activity in PHP type Ia patients. These patients exhibit characteristics of Albright hereditary osteodystrophy (AHO) and hypocalcemia, increased parathyroid hormone, and resistance to other Gsalpha protein-coupled hormones. AHO has a wide range of manifestations such as short stature, obesity, round face, subcutaneous ossification, and bone shortening in the hands and feet. In this study, we present the case of a 47-yr-old woman who was diagnosed with PHP type Ia with AHO. She showed tetany, dizziness, irritability to light, decreased visual acuity, cognitive impairment, and motor dysfunction. Direct sequencing identified a heterozygous missense mutation in exon 6 (c.466G>A, p.Asp156Asn) in GNAS1. To our knowledge, this case is the first report in Korea of PHP type Ia caused by a heterozygous missense mutation in exon 6 (c.466G>A, p.Asp156Asn) in GNAS1.
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Femenino , Humanos , Mareo , Exones , Pie , Mano , Hipocalcemia , Riñón , Corea (Geográfico) , Mutación Missense , Obesidad , Hormona Paratiroidea , Seudohipoparatiroidismo , Tetania , Agudeza VisualRESUMEN
Pseudohypoparathyroidism(PHP) is a rare genetic disorder.The main character is parathyroid hormone resistance,and some with typical Albright's Hereditary Osteodystrothy malformation.The wide range of PHP symptom spectrum may lead to miss or misdiagnosis.This paper reviewed and summarized the pathogenesis,manifestation and the progress on the diagnosis and treatment of PHP Ⅰ,so as to improve the diagnostic level of this disease.