Spontaneous pneumothorax and hemothorax frequently precede the arterial and intestinal complications of vascular Ehlers–Danlos syndrome

Shalhub, Sherene; Neptune, Enid; Sanchez, Daniel R.; Dua, Anahita; Arellano, Nelson; McDonnell, Nazli B.; Milewicz, Dianna M.

doi:10.1002/ajmg.a.61094

Cited by 33 publications

(22 citation statements)

References 27 publications

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“…3,5 An additional window of opportunity for early diagnosis is at the time of presenting with a spontaneous pneumothorax, because this entity seems to present at a younger age with male predominance compared with individuals presenting with intestinal or arterial events, as demonstrated in this series and in a recent report on a separate cohort of patients with vEDS. 24 This study demonstrates the limits related to the use of a diagnostic code when it does not discriminate among different bases for a common disorder. All 13 types of EDS are included in a single diagnostic code in both the ICD-9 and the ICD-10 (Q79.6).…”

Section: Discussionmentioning

confidence: 88%

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

Shalhub

Byers

Hicks

et al. 2020

Journal of Vascular Surgery

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Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. Methods: This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation. Results: Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P ¼ .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P ¼ .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P ¼ .13). There were no differences in mortality or age of mortality between the two cohorts.

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Section: Discussionmentioning

confidence: 88%

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

Shalhub

Byers

Hicks

et al. 2020

Journal of Vascular Surgery

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“…Approximately 98% of the vEDS cases are caused by a pathogenic variation in the COL3A1 gene [Mehta et al, 2012;Nasser et al 2013;Shalhub et al 2019]. COL3A1 (NG_007404.1) is located at chr2q31 and composed of 51 exons.…”

Section: Discussionmentioning

confidence: 99%

“…COL3A1 (NG_007404.1) is located at chr2q31 and composed of 51 exons. Mutations in this gene cause aortic aneurysms, aortic dissection and rupture, gastrointestinal hemorrhage and perforation, uterine rupture, pneumothorax, hemothorax, and sudden death in some cases [Germain 2007;Nasser et al 2013;Shalhub et al 2019]. More than 200 mutations in the COL3A1 gene have been described so far, all of which lead to synthesis of an abnormal type III collagen protein [Malfait et al, 2017].…”

Section: Discussionmentioning

confidence: 99%

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A Novel <b><i>COL3A1 </i></b>c.2644G>T; p.(Gly882Cys) Variant in a Turkish Family with Vascular Ehlers-Danlos Syndrome

Aydıner

Hancer

2020

Mol Syndromol

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Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disease, also known as EDS type IV. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000 with EDS type IV representing approximately 5-10% of the cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. vEDS diagnosis is a challenging process. Patients usually have different phenotypic features and are unaware of the diagnosis at the time of initial vascular complications. The authors report the case of a 39-year-old male patient with EDS type IV, who developed internal carotid artery dissection and was diagnosed with clinical findings, imaging modalities, and a novel pathogenic COL3A1 variant.

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“…Spontaneous pneumo(hemo)thorax was recently highlighted as an early manifestation of vEDS by frequently preceding a major arterial/intestinal event . Accordingly, the 2017 classification identified pneumothorax plus other suggestive vEDS features as a minimal criterion .…”

Section: Discussionmentioning

confidence: 99%

Application of the 2017 criteria for vascular Ehlers‐Danlos syndrome in 50 patients ascertained according to the Villefranche nosology

et al. 2019

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Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to heterozygous pathogenic COL3A1 variants. Arterial, intestinal, and/or uterine fragility is the disease hallmark and results in reduced life expectancy. The clinical diagnosis is not always straightforward and patients' selection for molecular confirmation depends on the characteristics of applied criteria, that is, the Villefranche criteria (in use until 2017) and their revision according to the new EDS nosology. Herein, we reassessed the clinical features of 50 molecularly proven vEDS patients, diagnosed according to the Villefranche nosology between 2000 and 2016,using the 2017 classification in order to explore its clinical application. Our findings indicate that the Villefranche criteria were particularly valuable for symptomatic patients, even if with a limited specificity. Our study also suggests that the revised vEDS criteria, although expected to be more specific, might have a poorer accuracy, principally in terms of sensitivity. Both sets of criteria are less effective in presymptomatic young patients, especially in the absence of a clear-cut family history.For these patients, the careful evaluation of the cutaneous, articular, and dysmorphic features and, above all, genetic testing remain crucial to set-up proper follow-up and surveillance before catastrophic vascular and intestinal events.

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Spontaneous pneumothorax and hemothorax frequently precede the arterial and intestinal complications of vascular Ehlers–Danlos syndrome

Cited by 33 publications

References 27 publications

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

A Novel <b><i>COL3A1 </i></b>c.2644G>T; p.(Gly882Cys) Variant in a Turkish Family with Vascular Ehlers-Danlos Syndrome

Application of the 2017 criteria for vascular Ehlers‐Danlos syndrome in 50 patients ascertained according to the Villefranche nosology

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