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Massive Axial and Appendicular Skeletal Deformities in Connection with Gorham-Stout Syndrome.

ABSTRACT: : Background: Etiological understanding is the corner stone in the management of skeletal deformities. Methods: Multi-centre study of patients with deformities in connection with diverse etiological backgrounds. We aimed to study four patients (one boy and three girls) with variable axial and appendicular deformities in connection with a vanishing bone disorder. Results: Axial deformities such as scoliosis, kyphoscoliosis, compressed fused vertebrae, appendicular fractures, dislocations, and vicious disorganization deformities of the joints were in connection with the vanishing bone disorder, namely Gorham-Stout syndrome. Conclusions: It is mandatory to establish proper clinical and radiological phenotypic characterization in children and adults presented with unusual skeletal deformities. Identifying the reason behind these deformities is the key factor to draw a comprehensive management plan.

SUBMITTER: Kaissi AA

PROVIDER: S-EPMC6631250 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Massive Axial and Appendicular Skeletal Deformities in Connection with Gorham-Stout Syndrome.

Kaissi Ali Al AA Bouchoucha Sami S Shboul Mohammad M Kenis Vladimir V Grill Franz F Ganger Rudolf R Kircher Susanne Gerit SG

Medicines (Basel, Switzerland) 20190507 2

: Background: Etiological understanding is the corner stone in the management of skeletal deformities. Methods: Multi-centre study of patients with deformities in connection with diverse etiological backgrounds. We aimed to study four patients (one boy and three girls) with variable axial and appendicular deformities in connection with a vanishing bone disorder. Results: Axial deformities such as scoliosis, kyphoscoliosis, compressed fused vertebrae, app ...[more]

PMID: 31067823

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A report of two children with Gorham-Stout disease.

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| S-EPMC6591827 | biostudies-literature

Gorham-Stout disease of spine accompanying chylothorax: a case description.

Project description: Not available

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Gorham-Stout syndrome in mainland China: a case series of 67 patients and review of the literature.

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KRAS-driven model of Gorham-Stout disease effectively treated with trametinib.

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Axial and appendicular skeletal transformations, ligament alterations, and motor neuron loss in Hoxc10 mutants.

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FoxD1-driven CCN2 deletion causes axial skeletal deformities, pulmonary hypoplasia, and neonatal asphyctic death.

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The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development.

Project description:Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll) gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In Drosophila, Dll is expressed in the distal portion of the developing appendages and is critical for the development of distal structures. In addition, human Dlx5 and Dlx6 homeobox genes have been identified as possible candidate genes for the autosomal dominant form of the split-hand/split-foot malformation (SHFM), a heterogeneous limb disorder characterized by missing central digits and claw-like distal extremities. Targeted inactivation of Dlx5 and Dlx6 genes in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities, leading to perinatal lethality. For the first time, Dlx/Dll gene products are shown to be critical regulators of mammalian limb development, as combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth.

| S-EPMC186247 | biostudies-literature

Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease.

Project description:BackgroundGeneralized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are rare complicated lymphatic malformations that occur in multiple body sites and are associated with significant morbidity and mortality. Treatment options have been limited, and conventional medical therapies have been generally ineffective. Emerging data suggest a role for sirolimus as a treatment option for complex lymphatic anomalies.ProcedureDisease response was evaluated by radiologic imaging, quality of life (QOL), and clinical status assessments in children and young adults with GLA and GSD from a multicenter systematic retrospective review of patients treated with oral sirolimus and the prospective phase 2 clinical trial assessing the efficacy and safety of sirolimus in complicated vascular anomalies (NCT00975819). Sirolimus dosing regimens and toxicities were also assessed.ResultsEighteen children and young adults with GLA (n = 13) or GSD (n = 5) received oral sirolimus. Fifteen patients (83%) had improvement in one or more aspects of their disease (QOL 78%, clinical status 72%, imaging 28%). No patients with bone involvement had progression of bone disease, and the majority had symptom or functional improvement on sirolimus. Improvement of pleural and pericardial effusion(s) occurred in 72% and 50% of affected patients; no effusions worsened on treatment.ConclusionsSirolimus appears effective at stabilizing or reducing signs/symptoms of disease in patients with GLA and GSD. Functional impairment and/or QOL improved in the majority of individuals with GLA and GSD with sirolimus treatment.

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Correction to: FoxD1-driven CCN2 deletion causes axial skeletal deformities, pulmonary hypoplasia, and neonatal asphyctic death.

Project description:Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs. Differentiation of FoxD1-progenitor derived pericytes into myofibroblasts involves CCN2 expression and contributes importantly to maladaptive tissue remodeling in for example kidney and lung fibrosis models. To generate a model for studying the contribution of CCN2 expression in FoxD1-progenitor derived cells to development of fibrotic tissue remodeling, we set out to establish a FoxD1Cre - CCN2flox/flox mouse colony. However, all double-transgenic mice died soon after birth due to asphyxia. Histopathological examination revealed a reduction in alveolar space and lung weight, and subtle axial (thoracic and cervical) skeletal deformities. Together with the previously reported association of a FoxD1 containing locus with human adolescent idiopathic scoliosis, our data suggest that the fatal pulmonary hypoplasia resulting from selective deletion of CCN2 from FoxD1-progenitor derived mesenchymal cells developed secondary to impaired breathing movements due to aberrant axial skeletogenesis.

| S-EPMC7176786 | biostudies-literature

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