Síndrome stiff skin: relato de caso

Amorim, Adriana Gutstein da Fonseca; Aidé, Márcia Kalil; Durães, Sandra Maria Barbosa; Rochael, Mayra Carrijo

doi:10.1590/s0365-05962011000700046

Cited by 15 publications

(4 citation statements)

References 16 publications

(8 reference statements)

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“…A number of treatments have been tried in individual cases, including steroids, immunosuppressant drugs, psoralens (light-sensitizing medications), and light therapy. These treatments have not been helpful in slowing or stopping disease evolution [ 55 ]. A paper discussed the possibility of using mycophenolate mofetil, which is a medication that suppresses the immune system, in combination with physical therapy to treat segmental SSS [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Fusco

Nardella

Augello

et al. 2020

IJMS

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Transforming growth factor β (TGF-β) superfamily signaling pathways are ubiquitous and essential for several cellular and physiological processes. The overexpression of TGF-β results in excessive fibrosis in multiple human disorders. Among them, stiff skin syndrome (SSS) is an ultrarare and untreatable condition characterized by the progressive thickening and hardening of the dermis, and acquired joint limitations. SSS is distinct in a widespread form, caused by recurrent germline variants of FBN1 encoding a key molecule of the TGF-β signaling, and a segmental form with unknown molecular basis. Here, we report a 12-year-old female with segmental SSS, affecting the right upper limb with acquired thickening of the dermis evident at the magnetic resonance imaging, and progressive limitation of the elbow and shoulder. To better explore the molecular and cellular mechanisms that drive segmental SSS, several functional studies on patient’s fibroblasts were employed. We hypothesized an impairment of TGF-β signaling and, consequently, a dysregulation of the associated downstream signaling. Lesional fibroblast studies showed a higher phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), increased levels of nuclear factor-kB (NFkB), and a nuclear accumulation of phosphorylated Smad2 via Western blot and microscopy analyses. Quantitative PCR expression analysis of genes encoding key extracellular matrix proteins revealed increased levels of COL1A1, COL3A1, AGT, LTBP and ITGB1, while zymography assay reported a reduced metalloproteinase 2 enzymatic activity. In vitro exposure of patient’s fibroblasts to losartan led to the partial restoration of normal transforming growth factor β (TGF-β) marker protein levels. Taken together, these data demonstrate that in our patient, segmental SSS is characterized by the overactivation of multiple TGF-β signaling pathways, which likely results in altered extracellular matrix composition and fibroblast homeostasis. Our results for the first time reported that aberrant TGF-β signaling may drive the pathogenesis of segmental SSS and might open the way to novel therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Fusco

Nardella

Augello

et al. 2020

IJMS

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“… 1 , 2 , 3 Characteristically, there are no systemic symptoms, such as Raynaud’s phenomenon, periungual changes, and visceral involvement, which helps to differentiate it from systemic sclerosis, localized cutaneous sclerosis, collagenomas, neonatal sclerema, scleromyxedema and mucopolysaccharidoses. 4 , 5 …”

mentioning

confidence: 99%

“… 9 Non-drug therapies, such as motor physical therapy, have been shown to be important in preventing muscle contractures and postural sequelae. 4 , 5 …”

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confidence: 99%

See 1 more Smart Citation

Stiff skin syndrome: long-term follow-up

Baka,

Rocha,

Pincelli

et al. 2024

Anais Brasileiros de Dermatologia

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Genetic Disorders of Collagen, Elastin and Dermal Matrix

Burrows

2016

Rook's Textbook of Dermatology, Ninth Edition

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The inherited disorders of connective tissue are a heterogeneous group of conditions characterized by defects involving primarily one element of the connective tissue: collagen, elastic fibre or other extracellular matrix proteins. Multisystem involvement is common and can be fatal. There is variable skin involvement but recognition of characteristic skin findings may provide an early diagnosis and identify those at risk of internal complications. This chapter covers the inherited disorders of collagen and elastic fibres, infantile stiff skin and premature ageing syndromes, disorders of ectopic calcification and abnormal mineralization, as well as other syndromes related to abnormal connective tissue.

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Síndrome stiff skin: relato de caso

Cited by 15 publications

References 16 publications

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Stiff skin syndrome: long-term follow-up

Genetic Disorders of Collagen, Elastin and Dermal Matrix

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