Classical-like Ehlers-Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

doi:10.1038/s41436-020-0850-1

. 2020 Oct;22(10):1576-1582.

doi: 10.1038/s41436-020-0850-1. Epub 2020 Jun 23.

Classical-like Ehlers-Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

Claire Green^#¹, Neeti Ghali^#², Rhoda Akilapa², Chloe Angwin², Duncan Baker³, Marion Bartlett², Jessica Bowen¹, Angela F Brady², Joanna Brock³, Erin Chamberlain⁴, Harveer Cheema³, Vivienne McConnell⁵, Renarta Crookes³, Hanadi Kazkaz⁶, Diana Johnson¹, F Michael Pope⁷, Anthony Vandersteen⁴, Glenda Sobey^#⁸, Fleur S van Dijk^#⁹

Affiliations

¹ National Ehlers Danlos Syndrome Service, Sheffield Children's Hospital, Sheffield, UK.
² National Ehlers Danlos Syndrome Service, London North West University Healthcare NHS Trust, Harrow, London, UK.
³ Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
⁴ Maritime Medical Genetics Service, IWK Health Centre, Halifax, NS, Canada.
⁵ Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast Health & Social Care Trust, Belfast, UK.
⁶ Rheumatology Department, University College Hospital, London, UK.
⁷ Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
⁸ National Ehlers Danlos Syndrome Service, Sheffield Children's Hospital, Sheffield, UK. glenda.sobey@nhs.net.
⁹ National Ehlers Danlos Syndrome Service, London North West University Healthcare NHS Trust, Harrow, London, UK. fleur.dijk@nhs.net.

^# Contributed equally.

PMID: 32572181
DOI: 10.1038/s41436-020-0850-1

Free article

Classical-like Ehlers-Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

Claire Green et al. Genet Med. 2020 Oct.

Free article

. 2020 Oct;22(10):1576-1582.

doi: 10.1038/s41436-020-0850-1. Epub 2020 Jun 23.

Authors

Affiliations

¹ National Ehlers Danlos Syndrome Service, Sheffield Children's Hospital, Sheffield, UK.
² National Ehlers Danlos Syndrome Service, London North West University Healthcare NHS Trust, Harrow, London, UK.
³ Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
⁴ Maritime Medical Genetics Service, IWK Health Centre, Halifax, NS, Canada.
⁵ Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast Health & Social Care Trust, Belfast, UK.
⁶ Rheumatology Department, University College Hospital, London, UK.
⁷ Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
⁸ National Ehlers Danlos Syndrome Service, Sheffield Children's Hospital, Sheffield, UK. glenda.sobey@nhs.net.
⁹ National Ehlers Danlos Syndrome Service, London North West University Healthcare NHS Trust, Harrow, London, UK. fleur.dijk@nhs.net.

^# Contributed equally.

PMID: 32572181
DOI: 10.1038/s41436-020-0850-1

Abstract

Purpose: Currently, 31 patients with classical-like EDS (clEDS) due to tenascin-X deficiency have been reported in the literature. We report on the clinical and molecular characteristics of 20 additional patients with clEDS to expand knowledge and to enable improved management of this rare genetic disorder.

Methods: Patients diagnosed with clEDS by the national EDS service in the UK (n = 21) and abroad (n = 1) were asked for consent for publication of their clinical and molecular data.

Results: Of 22 patients, 20 consented. All patients had typical features of clEDS: joint hypermobility, easy bruising, and skin hyperextensibility without atrophic scars. Importantly, 3/20 patients experienced gastrointestinal complications consisting of small or large bowel ruptures and one esophageal rupture. Other notable observations included two separate occurrences of spontaneous compartment syndrome, suspicion of nonaccidental injury due to significant bruising, and significant clinical variability regarding the debilitating effect of joint dislocations.

Conclusions: We propose a predisposition to tissue fragility, particularly of the gastrointestinal tract in patients with clEDS. As such, clinical and molecular confirmation of this diagnosis is essential. It is recommended to follow up these patients closely to understand the natural history to develop better recommendations for management.

Keywords: TNXB; classical-like Ehlers–Danlos syndrome; tenascin-X.

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References

1. Malfait F. Vascular aspects of the Ehlers–Danlos syndromes. Matrix Biol. 2018;71-72:380–395. - DOI
1. Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8–26. - DOI
1. Burch GH, Gong Y, Liu W, et al. Tenascin-X deficiency is associated with Ehlers–Danlos syndrome. Nat Genet. 1997;17:104–108. - DOI
1. Brady AF, Demirdas S, Fournel-Gigleux S, et al. The Ehlers–Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175:70–115. - DOI
1. Valcourt U, Alcaraz LB, Exposito JY, et al. Tenascin-X: beyond the architectural function. Cell Adh Migr. 2015;9:154–165. - DOI

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[1] Malfait F. Vascular aspects of the Ehlers–Danlos syndromes. Matrix Biol. 2018;71-72:380–395. - DOI

[2] Malfait F. Vascular aspects of the Ehlers–Danlos syndromes. Matrix Biol. 2018;71-72:380–395. - DOI

[3] Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8–26. - DOI

[4] Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8–26. - DOI

[5] Burch GH, Gong Y, Liu W, et al. Tenascin-X deficiency is associated with Ehlers–Danlos syndrome. Nat Genet. 1997;17:104–108. - DOI

[6] Burch GH, Gong Y, Liu W, et al. Tenascin-X deficiency is associated with Ehlers–Danlos syndrome. Nat Genet. 1997;17:104–108. - DOI

[7] Brady AF, Demirdas S, Fournel-Gigleux S, et al. The Ehlers–Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175:70–115. - DOI

[8] Brady AF, Demirdas S, Fournel-Gigleux S, et al. The Ehlers–Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175:70–115. - DOI

[9] Valcourt U, Alcaraz LB, Exposito JY, et al. Tenascin-X: beyond the architectural function. Cell Adh Migr. 2015;9:154–165. - DOI

[10] Valcourt U, Alcaraz LB, Exposito JY, et al. Tenascin-X: beyond the architectural function. Cell Adh Migr. 2015;9:154–165. - DOI

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Classical-like Ehlers-Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

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Classical-like Ehlers-Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility

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