A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis
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A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis. / Shalhub, Sherene; Byers, Peter H; Hicks, Kelli L; Coleman, Dawn M; Davis, Frank M; De Caridi, Giovanni; Weaver, K Nicole; Miller, Erin M; Schermerhorn, Marc L; Shean, Katie; Oderich, Gustavo; Ribeiro, Mauricio; Nishikawa, Cole; Charlton-Ouw, Kristofer; Behrendt, Christian-Alexander; Debus, E Sebastian; von Kodolitsch, Yskert; Zarkowsky, Devin; Powell, Richard J; Pepin, Melanie; Milewicz, Dianna M; Regalado, Ellen S; Lawrence, Peter F; Woo, Karen.
In: J VASC SURG, Vol. 71, No. 1, 09.01.2020, p. 149-157.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis
AU - Shalhub, Sherene
AU - Byers, Peter H
AU - Hicks, Kelli L
AU - Coleman, Dawn M
AU - Davis, Frank M
AU - De Caridi, Giovanni
AU - Weaver, K Nicole
AU - Miller, Erin M
AU - Schermerhorn, Marc L
AU - Shean, Katie
AU - Oderich, Gustavo
AU - Ribeiro, Mauricio
AU - Nishikawa, Cole
AU - Charlton-Ouw, Kristofer
AU - Behrendt, Christian-Alexander
AU - Debus, E Sebastian
AU - von Kodolitsch, Yskert
AU - Zarkowsky, Devin
AU - Powell, Richard J
AU - Pepin, Melanie
AU - Milewicz, Dianna M
AU - Regalado, Ellen S
AU - Lawrence, Peter F
AU - Woo, Karen
N1 - Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
PY - 2020/1/9
Y1 - 2020/1/9
N2 - 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 = .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 = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.CONCLUSIONS: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.
AB - 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 = .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 = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.CONCLUSIONS: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.
KW - Adolescent
KW - Adult
KW - Collagen Type III/genetics
KW - Cross-Sectional Studies
KW - DNA Mutational Analysis
KW - Diagnosis, Differential
KW - Ehlers-Danlos Syndrome/complications
KW - Female
KW - Genetic Predisposition to Disease
KW - Germany
KW - Humans
KW - Italy
KW - Male
KW - Middle Aged
KW - Mutation
KW - Phenotype
KW - Predictive Value of Tests
KW - Prognosis
KW - Retrospective Studies
KW - Risk Assessment
KW - Risk Factors
KW - United States
KW - Young Adult
U2 - 10.1016/j.jvs.2019.04.487
DO - 10.1016/j.jvs.2019.04.487
M3 - SCORING: Journal article
C2 - 31353273
VL - 71
SP - 149
EP - 157
JO - J VASC SURG
JF - J VASC SURG
SN - 0741-5214
IS - 1
ER -
