The Role of Cutaneous Manifestations in the Diagnosis of the Ehlers-Danlos Syndromes

Overview

Journal Skin Health Dis

Publisher Oxford University Press

Specialty Dermatology

Date 2023 Feb 8

PMID 36751332

Authors

Natasha Stembridge

Brent J Doolan

Mark E Lavallee

Ingrid Hausser

F Michael Pope

Suranjith L Seneviratne

Ingrid M Winship

Nigel P Burrows

Affiliations

Soon will be listed here.

Abstract

The Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with features of skin hyperextensibility, joint hypermobility, abnormal scarring and fragility of skin, blood vessels and some organs. The disease is generally diagnosed through the cluster of clinical features, though the addition of genetic analysis is the gold standard for diagnosis of most subtypes. All subtypes display skin manifestations, which are essential to the accurate clinical diagnosis of the condition. Furthermore, cutaneous features can be the first and/or only presenting feature in some cases of EDS and thus understanding these signs is vital for diagnosis. This review focuses on particular cutaneous features of each EDS subtype and their clinical importance. Provision of a specific diagnosis is important for management, prognosis and genetic counselling, often for family members beyond the individual.

Citing Articles

Extracutaneous features and complications of the Ehlers-Danlos syndromes: A systematic review.

Doolan B, Lavallee M, Hausser I, Schubart J, Pope F, Seneviratne S Front Med (Lausanne). 2023; 10:1053466.

PMID: 36756177 PMC: 9899794. DOI: 10.3389/fmed.2023.1053466.

The role of cutaneous manifestations in the diagnosis of the Ehlers-Danlos syndromes.

Stembridge N, Doolan B, Lavallee M, Hausser I, Pope F, Seneviratne S Skin Health Dis. 2023; 3(1):e140.

PMID: 36751332 PMC: 9892481. DOI: 10.1002/ski2.140.

References

Colombi M, Dordoni C, Venturini M, Zanca A, Calzavara-Pinton P, Ritelli M . Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three-generation family without cardiovascular events, and literature review. Am J Med Genet A. 2017; 173(2):524-530. DOI: 10.1002/ajmg.a.38035. View

Reardon W, Donnai D . Dysmorphology demystified. Arch Dis Child Fetal Neonatal Ed. 2007; 92(3):F225-9. PMC: 2675338. DOI: 10.1136/adc.2006.110619. View

Angwin C, Brady A, Colombi M, Ferguson D, Pollitt R, Pope F . Absence of Collagen Flowers on Electron Microscopy and Identification of (Likely) Pathogenic Variants in Two Patients. Genes (Basel). 2019; 10(10). PMC: 6826538. DOI: 10.3390/genes10100762. View

Lu Y, Wang Y, Rauch F, Li H, Zhang Y, Zhai N . Osteogenesis imperfecta type III/Ehlers-Danlos overlap syndrome in a Chinese man. Intractable Rare Dis Res. 2018; 7(1):37-41. PMC: 5849623. DOI: 10.5582/irdr.2018.01010. View

Bowen J, Sobey G, Burrows N, Colombi M, Lavallee M, Malfait F . Ehlers-Danlos syndrome, classical type. Am J Med Genet C Semin Med Genet. 2017; 175(1):27-39. DOI: 10.1002/ajmg.c.31548. View

Proske S, Hartschuh W, Enk A, Hausser I . [Ehlers-Danlos syndrome--20 years experience with diagnosis and classification at the university skin clinic of Heidelberg]. J Dtsch Dermatol Ges. 2006; 4(4):308-18. DOI: 10.1111/j.1610-0387.2006.05958.x. View

Legrand A, Devriese M, Dupuis-Girod S, Simian C, Venisse A, Mazzella J . Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome. Genet Med. 2018; 21(7):1568-1575. DOI: 10.1038/s41436-018-0356-2. View

Pallesen K, Hein Lindahl K, Bygum A . Elastosis perforans serpiginosa related to vascular Ehlers-Danlos syndrome. Dermatol Online J. 2019; 25(3). View

De Paepe A, Malfait F . The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet. 2012; 82(1):1-11. DOI: 10.1111/j.1399-0004.2012.01858.x. View

10.

de Almeida Jr H, Bicca E, Rocha N, de Castro L . Light and electron microscopy of classical Ehlers-Danlos syndrome. Am J Dermatopathol. 2012; 35(1):102-5. DOI: 10.1097/DAD.0b013e3182713293. View

11.

Castori M . Ehlers-Danlos syndrome(s) mimicking child abuse: Is there an impact on clinical practice?. Am J Med Genet C Semin Med Genet. 2015; 169(4):289-92. DOI: 10.1002/ajmg.c.31460. View

12.

Baumann M, Giunta C, Krabichler B, Ruschendorf F, Zoppi N, Colombi M . Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss. Am J Hum Genet. 2012; 90(2):201-16. PMC: 3276673. DOI: 10.1016/j.ajhg.2011.12.004. View

13.

Angwin C, Ghali N, Baker D, Brady A, Pope F, Vandersteen A . Electron microscopy in the diagnosis of Ehlers-Danlos syndromes: correlation with clinical and genetic investigations. Br J Dermatol. 2019; 182(3):698-707. DOI: 10.1111/bjd.18165. View

14.

Colombi M, Dordoni C, Venturini M, Ciaccio C, Morlino S, Chiarelli N . Spectrum of mucocutaneous, ocular and facial features and delineation of novel presentations in 62 classical Ehlers-Danlos syndrome patients. Clin Genet. 2017; 92(6):624-631. DOI: 10.1111/cge.13052. View

15.

Syx D, De Wandele I, Symoens S, De Rycke R, Hougrand O, Voermans N . Bi-allelic AEBP1 mutations in two patients with Ehlers-Danlos syndrome. Hum Mol Genet. 2019; 28(11):1853-1864. DOI: 10.1093/hmg/ddz024. View

16.

Chiarelli N, Ritelli M, Zoppi N, Colombi M . Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes. Genes (Basel). 2019; 10(8). PMC: 6723307. DOI: 10.3390/genes10080609. View

17.

Brady A, Demirdas S, Fournel-Gigleux S, Ghali N, Giunta C, Kapferer-Seebacher I . The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017; 175(1):70-115. DOI: 10.1002/ajmg.c.31550. View

18.

Stembridge N, Doolan B, Lavallee M, Hausser I, Pope F, Seneviratne S . The role of cutaneous manifestations in the diagnosis of the Ehlers-Danlos syndromes. Skin Health Dis. 2023; 3(1):e140. PMC: 9892481. DOI: 10.1002/ski2.140. View

19.

Pope F, Narcisi P, Nicholls A, Germaine D, Pals G, Richards A . COL3A1 mutations cause variable clinical phenotypes including acrogeria and vascular rupture. Br J Dermatol. 1996; 135(2):163-81. View

20.

Malfait F, Castori M, Francomano C, Giunta C, Kosho T, Byers P . The Ehlers-Danlos syndromes. Nat Rev Dis Primers. 2020; 6(1):64. DOI: 10.1038/s41572-020-0194-9. View