title: Six uneventful pregnancy outcomes in an extended vascular Ehlers-Danlos syndrome family.
abstract: Vascular Ehlers-Danlos Syndrome (vEDS) is caused by heterozygous mutations in COL3A1 and is characterized by fragile vasculature and hollow organs, with a high risk of catastrophic events at a young age. During pregnancy and delivery, maternal mortality rates up until 25% have been reported. However, recent pedigree analysis reported a substantial lower pregnancy-related mortality rate of 4.9%. Here, we describe an extended vEDS family with multiple uneventful pregnancy outcomes. In the proband, a 37-year-old woman, DNA-analysis because of an asymptomatic iliac artery dissection revealed a pathogenic mutation in COL3A1 (c.980G>A; p. Gly327Asp). She had had three uneventful vaginal deliveries. At the time of diagnosis, her 33-year-old niece was 25 weeks pregnant. She had had one uneventful vaginal delivery. Targeted DNA-analysis revealed that she was carrier of the COL3A1 mutation. Ultrasound detected an aneurysm in the abdominal aorta with likely a dissection. An uneventful elective cesarean section was performed at a gestational age of 37 weeks. The 40-year-old sister of our proband had had one uneventful vaginal delivery and an active pregnancy wish. Cascade DNA-screening showed her to carry the COL3A1 mutation. Computed Tomography Angiography (CTA) of her aorta revealed a type B dissection with the most proximal entry tear just below the superior mesenteric artery. Pregnancy was therefore discouraged. This familial case illustrates the complexity and challenges of reproductive decision-making in a potentially lethal condition as vEDS, and highlights the importance of a multidisciplinary approach. Moreover, it suggests that previous pregnancy-related risks of vEDS may be overestimated. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Annette F
authors.initials: AF
authors.lastname: Baas
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Wilko
authors.initials: W
authors.lastname: Spiering
authors.affiliation: Department Vascular Surgery, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Lieve
authors.initials: L
authors.lastname: Page-Christiaens
authors.affiliation: Department of Anesthesiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Ingrid C M
authors.initials: IC
authors.lastname: Beenakkers
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.affiliation: Department of Radiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Evert-Jan P A
authors.initials: EP
authors.lastname: Vonken
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: van der Smagt
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Nine V
authors.initials: NV
authors.lastname: Knoers
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Steven V
authors.initials: SV
authors.lastname: Koenen
authors.affiliation: Department Vascular Surgery, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Joost A
authors.initials: JA
authors.lastname: van Herwaarden
authors.affiliation: Department of Cardiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Gertjan Tj
authors.initials: GT
authors.lastname: Sieswerda
mesh_terms: D000328:Adult; D000368:Aged; D000066491:Clinical Decision-Making; D024061:Collagen Type III / Q000235:genetics; D019468:Disease Management; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome
chemical_list: D024061:Collagen Type III
keywords: COL3A1; aneurysm; delivery; dissection; pregnancy; vascular Ehlers­­-Danlos Syndrome (vEDS)