TY - JOUR
T1 - Six uneventful pregnancy outcomes in an extended vascular Ehlers-Danlos syndrome family
AU - Baas, Annette F.
AU - Spiering, Wilko
AU - Moll, Frans L.
AU - Page-Christiaens, Lieve
AU - Beenakkers, Ingrid C M
AU - Dooijes, Dennis
AU - Vonken, Evert Jan P A
AU - van der Smagt, Jasper J.
AU - Knoers, Nine V.
AU - Koenen, Steven V.
AU - van Herwaarden, Joost A.
AU - Sieswerda, Gertjan T J
N1 - Funding Information:
A.F. Baas was supported by a grant from the Dr. E. Dekker Program of The Netherlands Heart Foundation (2015T041).
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
KW - COL3A1
KW - aneurysm
KW - delivery
KW - dissection
KW - pregnancy
KW - vascular Ehlers–Danlos Syndrome (vEDS)
UR - http://www.scopus.com/inward/record.url?scp=84999041239&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.38033
DO - 10.1002/ajmg.a.38033
M3 - Article
C2 - 28102592
AN - SCOPUS:84999041239
SN - 1552-4825
VL - 173
SP - 519
EP - 523
JO - American Journal of Medical Genetics. Part A
JF - American Journal of Medical Genetics. Part A
IS - 2
ER -