Abstract
With advances in medical care, many women with genetic conditions previously known to decrease life expectancy are reaching childbearing age. Thus, it is important to understand the management of patients in the preconception, antepartum, and postpartum periods as they pose a unique challenge to the obstetrician. Most rare disorders lack well-established clinical guidelines for management in pregnancy. Existing data stem from case reports, case series, and expert opinion. We aim to summarize these recommendations and develop a clinical reference for managing reproductive age women with these conditions. We review recommendations for women with inborn errors in metabolism, connective tissue disorders, skeletal dysplasia, and selected single gene disorders. In all cases, it is crucial to employ a multidisciplinary team to optimize care for patients with rare disease before, during, and immediately after their pregnancies. The emphasis on expert consensus recommendations in the guidance of obstetric care is a signal that more studies are needed to determine best practices.
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References
Andersson C, Innala E, Bäckström T (2003) Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden. J Intern Med 254(2):176–183
Argov Z, de Visser M (2009) What we do not know about pregnancy in hereditary neuromuscular disorders. Neuromuscul Disord 19(10):675–679. https://doi.org/10.1016/j.nmd.2009.07.004
Awater C, Zerres K, Rudnik-Schöneborn S (2012) Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients. Eur J Obstet Gynecol Reprod Biol 162(2):153–159. https://doi.org/10.1016/j.ejogrb.2012.02.020
Baas AF, Spiering W, Moll FL et al (2016) Six uneventful pregnancy outcomes in an extended vascular ehlers—danlos syndrome family. Am J Med Genet. https://doi.org/10.1002/ajmg.a.38033
Bird TD (1993) Myotonic dystrophy type 1. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/20301344. Accessed 12 July 1993
Camp KM, Parisi MA, Acosta PB et al (2014) Phenylketonuria scientific review conference: state of the science and future research needs. Mol Genet Metab 112(2):87–122. https://doi.org/10.1016/j.ymgme.2014.02.013
Chuang DT, Shih VE (2001) Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 1971–2006
Deegan PB, Baehner AF, Barba Romero M-A et al (2005) Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet 43(4):347–352. https://doi.org/10.1136/jmg.2005.036327
Dietz H (1993) Marfan syndrome. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/20301510. Accessed 12 Oct 1993
Donnelly RT, Pinto NM, Kocolas I, Yetman AT (2012) The immediate and long-term impact of pregnancy on aortic growth rate and mortality in women with Marfan syndrome. J Am Coll Cardiol 60(3):224–229
Elder G, Harper P, Badminton M, Sandberg S, Deybach J-C (2013) The incidence of inherited porphyrias in Europe. J Inherit Metab Dis 36(5):849–857. https://doi.org/10.1007/s10545-012-9544-4
Erez Y, Ezra YRN (2008) Ehlers–Danlos type IV in pregnancy. A case report and a literature review. Fetal Diagn Ther 23:7–9
Evans DG (2012) Are we ready for targeted early breast cancer detection strategies in women with NF1 aged 30-49 years? Am J Med Genet A. 158A(12):3054–3055
Evans DGR, Baser ME, McGaughran J, Sharif S, Howard E, Moran A (2002) Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 39(5):311–314
Friedman J (1993) Neurofibromatosis 1. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/20301288. Accessed 17 May 1993
Goland S, Elkayam U (2017) Pregnancy and marfan syndrome. Ann Cardiothorac Surg 6(6):642–653. https://doi.org/10.21037/acs.2017.10.07
Grünewald S, Hinrichs F, Wendel U (1998) Pregnancy in a woman with maple syrup urine disease. J Inherit Metab Dis 21:89–94
Hammond RON (2012) Ehlers Danlos syndrome type IV and pregnancy. Arch Gynecol Obstet 281:51–54
Iwafuchi Y, Maruyama H, Morioka T et al (2017) Enzyme replacement therapy in a patient of heterozygous Fabry disease: clinical and pathological evaluations by repeat kidney biopsy and a successful pregnancy. CEN Case Rep 6(2):210–214. https://doi.org/10.1007/s13730-017-0277-y
Kim SY, Wolfe DS, Taub CC (2018) Cardiovascular outcomes of pregnancy in Marfan’s syndrome patients: a literature review. Congenit Heart Dis 13(2):203–209. https://doi.org/10.1111/chd.12546
Koch R, Hanley W, Levy H et al (2003) The maternal phenylketonuria international study: 1984–2002. Pediatrics 112(6 Pt 2):1523–1529
Lammert M, Friedman JM, Kluwe L, Mautner VF (2005) Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol 141:71–74
Leppävirta J, Kallionpää RA, Uusitalo E et al (2017) The pregnancy in neurofibromatosis 1: a retrospective register-based total population study. Am J Med Genet. https://doi.org/10.1002/ajmg.a.38372
Leslie ND, Valencia CA, Strauss AW, Zhang K (1993) Very long-chain acyl-coenzyme A dehydrogenase deficiency. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/20301763. Accessed 4 Jan 1993
Lichter-Konecki U, Caldovic L, Morizono H, Simpson K (1993) Ornithine transcarbamylase deficiency. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/24006547. Accessed 14 Apr 1993
Lurie S, Manor MHZ (1998) The threat of type IV Ehlers–Danlos syndrome on maternal well-being during pregnancy: early delivery may make the difference. J Obstet Gynaecol (Lahore) 18:245–248
Makatsariya A, Radetskaya L, Bitsadze V, Khizroeva J, Khamani N, Makatsariya N (2018) Prenatal care and labor in patients with mesenchymal dysplasias (Marfan syndrome, Ehlers–Danlos syndrome, hereditary hemorrhagic telangiectasia). J Matern Neonatal Med. https://doi.org/10.1080/14767058.2018.1493102
Mehta A, Hughes DA (1993) Fabry disease. University of Washington, Seattle
Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281(3):249–254
Mendez-Figueroa H, Shchelochkov OA, Shaibani A, Aagaard-Tillery K, Shinawi MS (2010) Clinical and biochemical improvement of very long-chain acyl-CoA dehydrogenase deficiency in pregnancy. J Perinatol 30(8):558–562. https://doi.org/10.1038/jp.2009.198
Murray ML, Pepin M, Peterson SBP (2014) Pregnancy-related deaths and complications in women with vascular Ehlers–Danlos syndrome. Genet Med. 16:874–880
Pauli RM, Legare JM (1993) Achondroplasia. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/20301331. Accessed 10 May 1993
Pepin MG, Murray ML, Byers PH (1993) Vascular Ehlers–Danlos syndrome. GeneReviews®. http://www.ncbi.nlm.nih.gov/pubmed/20301667. Accessed 19 Nov 1993
Platt LD, Koch R, Hanley WB et al (2000) The international study of pregnancy outcome in women with maternal phenylketonuria: report of a 12-year study. Am J Obstet Gynecol 182(2):326–333
Preece MA, Green A (2002) Pregnancy and inherited metabolic disorders: maternal and fetal complications. Ann Clin Biochem 39:444–455
Regier DS, Greene CL (1993) Phenylalanine hydroxylase deficiency. University of Washington, Seattle
Roth TM, Petty EM, Barald KF (2008) The role of steroid hormones in the NF1 phenotype: focus on pregnancy. Am J Med Genet A 146A:1624–1633
Rowe PC, Newman SL, Brusilow SW (1986) Natural history of syptomatic partial ornithine transcarbamylase deficiency. N Engl J Med 314(9):541–547. https://doi.org/10.1056/NEJM198602273140903
Savarirayan R, Rossiter JP, Hoover-Fong JE et al (2018) Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2018.07.017
Sillence DO, Senn A, Danks DM (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16:101–116
Steiner RD, Adsit J, Basel D (1993–2019) COL1A1/2-related osteogenesis imperfecta. 2005 Jan 28 [Updated 2013 Feb 14]. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews® (internet). University of Washington, Seattle
Tasci ES, Bicik Z (2015) Safe and successful treatment with agalsidase beta during pregnancy in Fabry disease. Iran J Kidney Dis 9(5):406–408. https://doi.org/10.1006/exnr.1999.7349
Tchan M, Westbrook M, Wilcox G et al (2013) The management of pregnancy in maple syrup urine disease: experience with two patients. JIMD Rep 10:113–117. https://doi.org/10.1007/8904
Terry AR, Barker FG, Leffert L, Bateman BT, Souter I, Plotkin SR (2013) Neurofibromatosis type 1 and pregnancy complications: a population-based study. Am J Obstet Gynecol 209:46
Tessier R, Nowak E, Assoun M et al (2012) Maternal phenylketonuria: low phenylalanine might increase the risk of intra uterine growth retardation. J Inherit Metab Dis 35:993–999
Theadom A, Rodrigues M, Roxburgh R et al (2014) Prevalence of muscular dystrophies: a systematic literature review. Neuroepidemiology 43(3–4):259–268. https://doi.org/10.1159/000369343
Veiga-Fernandez A, Joigneau Prieto L, Alvarez T et al (2019) Perinatal diagnosis and management of early-onset Marfan syndrome: case report and systematic review. J Matern Fetal Neonatal Med. https://doi.org/10.1080/14767058.2018.1552935
Vellekoop P, Diekman EF, van Tuijl I, de Vries MMC, van Hasselt PM, Visser G (2011) Perioperative measures in very long chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab 103(1):96–97. https://doi.org/10.1016/j.ymgme.2011.01.010
Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, Pearson K, Romitti PA, Shaw GM, Hecht JT (2008) The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. Am J Med Genet A 146A:2385–2389
Wendt S, Whybra C, Kampmann C, Teichmann E, Beck M (2005) Successful pregnancy outcome in a patient with Fabry disease receiving enzyme replacement therapy with agalsidase alfa. J Inherit Metab Dis 28(5):787–788. https://doi.org/10.1007/s10545-005-0018-9
Whatley SD, Badminton MN (1993) Acute intermittent porphyria. University of Washington, Seattle
Yamamoto H, Tachibana D, Tajima G et al (2015) Successful management of pregnancy with very-long-chain acyl-coenzyme A dehydrogenase deficiency. J Obstet Gynaecol Res 41(7):1126–1128. https://doi.org/10.1111/jog.12672
Zaki M, Boyd PA, Impey L, Roberts A, Chamberlain P (2007) Congenital myotonic dystrophy: prenatal ultrasound findings and pregnancy outcome. Ultrasound Obstet Gynecol 29(3):284–288. https://doi.org/10.1002/uog.3859
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Stone, J., Reed, D. Maternal genetic diseases: potential concerns for mother and baby. Hum Genet 139, 1173–1182 (2020). https://doi.org/10.1007/s00439-019-02086-6
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DOI: https://doi.org/10.1007/s00439-019-02086-6