Gorham-Stout Disease: a Clinical Case Report and Immunological Mechanisms in Bone Erosion

Franco-Barrera, María José; Zavala-Cerna, María Guadalupe; Aguilar-Portillo, Georgina; Sánchez-Gomez, Diana Brisa; Torres-Bugarı́n, Olivia; Franco-Barrera, Miguel Angel; Roa-Encarnacion, Carlos Manuel

doi:10.1007/s12016-016-8594-z

Cited by 20 publications

(17 citation statements)

References 37 publications

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“…After CES had yielded negative results, we performed aCGH, which provided no relevant findings. Ultimately, the patient was diagnosed with Gorham-Stout Disease (GSD), a rare disorder characterized by angiogenesis, lymphangiomatosis, and severe bone resorption (106). The exact cause of GSD is unknown and no environmental, immunological or genetic risk factors have been identified.…”

Section: Resultsmentioning

confidence: 99%

Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing: Expected and Unexpected Findings

et al. 2019

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Primary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of genetic defects in PID patients in daily clinical practice. Several NGS approaches are available, from the unbiased whole exome sequencing (WES) to specific gene panels. Here, we report on a 3-year experience with clinical exome sequencing (CES) for genetic diagnosis of PIDs. We used the TruSight One sequencing panel, which includes 4,813 disease-associated genes, in 61 unrelated patients (pediatric and adults). The analysis was done in 2 steps: first, we focused on a virtual PID panel and then, we expanded the analysis to the remaining genes. A molecular diagnosis was achieved in 19 (31%) patients: 12 (20%) with mutations in genes included in the virtual PID panel and 7 (11%) with mutations in other genes. These latter cases provided interesting and somewhat unexpected findings that expand the clinical and genetic spectra of PID-related disorders, and are useful to consider in the differential diagnosis. We also discuss 5 patients (8%) with incomplete genotypes or variants of uncertain significance. Finally, we address the limitations of CES exemplified by 7 patients (11%) with negative results on CES who were later diagnosed by other approaches (more specific PID panels, WES, and comparative genomic hybridization array). In summary, the genetic diagnosis rate using CES was 31% (including a description of 12 novel mutations), which rose to 42% after including diagnoses achieved by later use of other techniques. The description of patients with mutations in genes not included in the PID classification illustrates the heterogeneity and complexity of PID-related disorders.

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Section: Resultsmentioning

confidence: 99%

Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing: Expected and Unexpected Findings

et al. 2019

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“…It is considered that activation of the osteoclastogenic process is induced by immune mechanisms in affected bone tissue because the number of osteoclasts increases in the GSD lesion. 31 Alternatively, osteolysis could be caused by the abnormal proliferation of lymphatic vessels compressing bone. Moreover, the activity of osteoclasts is influenced by some cytokines that are secreted by the lymphatic endothelial cells.…”

Section: Discussion Of Findings and Relevant Literaturementioning

confidence: 99%

Generalized Lymphatic Anomaly and Gorham–Stout Disease: Overview and Recent Insights

Ozeki

Fukao

2019

Advances in Wound Care

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Significance: Generalized lymphatic anomaly and Gorham–Stout disease are extremely rare diseases with severe symptoms and poor prognosis. The etiology and clinical presentation of the patients remain poorly defined, but recent research has attempted to determine the pathogenesis of these diseases. Recent Advances: In recent years, the characteristics of complex lymphatic anomalies have been revealed. Kaposiform lymphangiomatosis is recognized as a new entity that has an aggressive course and poor prognosis. Genetic analysis revealed somatic mutations in genes associated with the phosphoinositide 3-kinase (PI3K) pathway in lymphatic malformation lesions. Somatic NRAS mutation in lymphatic endothelium from a generalized lymphatic anomaly patient was also detected as a potential cause of disease. Furthermore, studies demonstrated the efficacy of the mammalian target of rapamycin (mTOR) inhibitor sirolimus for these lymphatic diseases. Critical Issues: These diseases have overlapping symptoms, imaging features, and complications, leading to difficulty in their differential diagnosis. In addition, there are no standard therapies. Therefore, we need to determine the differences among these diseases to not only diagnose but also treat them appropriately. Future Directions: Further investigations should reveal differences in the clinical features and findings of radiological, pathological, and genetic examinations to manage each disease appropriately. Somatic mutation in genes encoding RAS/PI3K/mTOR signaling pathway components could be associated with the pathogenesis of these diseases and may be novel targets for drug therapies.

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“…As it is known that GSD osteolysis occurs adjacent to local proliferation of lymphatic vessels, the activation of osteoclasts and lymphangiogenesis is essential for the progress of GSD [21]; lymph is frequently seen in the osteolytic lesions. Franco-Barrera et al [22] reported that the activation of the osteoclastogenic process that affects bone tissue is induced by immune mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

Tian

Wang

et al. 2020

BMC Musculoskelet Disord

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Background: Gorham-Stout disease (GSD) is a rare disease characterized by bone lesions and osteolysis. Therapy usually involves surgical resection. Sirolimus (Rapamycin) is used in some patients with GSD but the efficacy and safety of Sirolimus remains unclear. We propose that Sirolimus may be a novel therapeutic for GSD and present a case and review of literature that supports this. Case presentation: We presented a 1-year-old boy with GSD involving osteolysis of the right humerus with fracture of the left femur complicated by an effusion in the right pleural cavity. X-rays showed osteolysis in the right clavicle. A large pleural effusion was observed on the right-side, and the left lung was significantly compressed. Xrays also showed a fracture of the left femur. A femoral biopsy was performed that showed necrotic tissue in the cortical bone and a large number of irregularly shaped capillaries that proliferated within the necrotic tissue. Dilated lymphatic vessels were seen adjacent to the cortex, with fibrous tissue hyperplasia. We prescribed sirolimus, which is an oral mTOR inhibitor, for two consecutive years. The boy recovered well without other progressive bone lesions and participates in normal daily activities. His growth and development are the same as that of his peers. Discussion and conclusion: Gorham-Stout disease is a rare and enigmatic disease characterized by the presentation of an intraosseous lymphatic anomaly (LM), which results in progressive bone resorption. Based on this case report and a literature review, we conclude that sirolimus may be an effective alternative medication for GSD.

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Gorham-Stout Disease: a Clinical Case Report and Immunological Mechanisms in Bone Erosion

Cited by 20 publications

References 37 publications

Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing: Expected and Unexpected Findings

Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing: Expected and Unexpected Findings

Generalized Lymphatic Anomaly and Gorham–Stout Disease: Overview and Recent Insights

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

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