Abstract
PIK3CA-related overgrowth spectrum (PROS) refers to a group of disorders of segmental overgrowth caused by mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) PROS is an umbrella term that includes several diagnostic entities, including congenital lipomatous overgrowth (CLOVES), fibroadipose hyperplasia (FAH), Klippel-Trenaunay Syndrome (KTS), isolated low flow vascular malformations (e.g. lymphatic and venous malformations), megalencephaly syndromes and focal cortical dysplasias, among others. Although many of these disorders are clinically distinct, there is a great deal of overlap, leading to the utility of considering them a spectrum of disorders due to post-zygotic activating mutations in the gene PIK3CA. In this chapter we review the phenotypic spectrum of these disorders, their clinical and molecular diagnosis, as well as their pathophysiology and management.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
McGinn S, Gut IG. DNA sequencing – spanning the generations. New Biotechnol. 2013;30(4):366–72.
*Koboldt DC, Steinberg KM, Larson DE, Wilson RK, Mardis ER. The next-generation sequencing revolution and its impact on genomics. Cell. 2013;155(1):27–38.
Shendure J, Balasubramanian S, Church GM, et al. DNA sequencing at 40: past, present and future. Nature. 2017;550(7676):345–53.
Koboldt DC, Larson DE, Wilson RK. Using VarScan 2 for germline variant calling and somatic mutation detection. Curr Protoc Bioinformatics. 2013;44:15.4.1–17.
***Luks VL, Kamitaki N, Vivero MP, et al. Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. J Pediatr. 2015;166(4):1048–54.e1–5.Accessed 20150330; 12/17/2015 5:54:01 PM. https://doi.org/10.1016/j.jpeds.2014.12.069.
Mirzaa G, Timms AE, Conti V, et al. PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution. JCI Insight. 2016;1(9):e87623.
***Limaye N, Kangas J, Mendola A, et al. Somatic activating PIK3CA mutations cause venous malformation. Am J Hum Genet. 2015;97(6):914–21.
Sanger F. Sequences, sequences, and sequences. Annu Rev Biochem. 1988;57:1–28.
Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291(5507):1304–51.
**Subramanian G, Adams MD, Venter JC, Broder S. Implications of the human genome for understanding human biology and medicine. JAMA. 2001;286(18):2296–307.
International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004;431(7011):931–45.
Organick L, Ang SD, Chen YJ, et al. Random access in large-scale DNA data storage. Nat Biotechnol. 2018;36(3):242–8.
Ng SB, Turner EH, Robertson PD, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):272–6.
Choi M, Scholl UI, Ji W, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A. 2009;106(45):19096–101.
Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci U S A. 2008;105(42):16266–71.
Shovlin CL, Hughes JM, Tuddenham EG, et al. A gene for hereditary haemorrhagic telangiectasia maps to chromosome 9q3. Nat Genet. 1994;6(2):205–9.
McDonald J, Gedge F, Burdette A, et al. Multiple sequence variants in hereditary hemorrhagic telangiectasia cases: illustration of complexity in molecular diagnostic interpretation. J Mol Diagn. 2009;11(6):569–75.
McDonald J, Damjanovich K, Millson A, et al. Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis. Clin Genet. 2011;79(4):335–44. Accessed 20110304; 12/17/2015 5:54:01 PM. https://doi.org/10.1111/j.1399-0004.2010.01596.x.
McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med. 2011;13(7):607–16. Accessed 20110708; 12/17/2015 5:42:12 PM. https://doi.org/10.1097/GIM.0b013e3182136d32.
McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead K, Stevenson DA, Bayrak-Toydemir P. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era. Front Genet. 2015;6:1.
Shirley MD, Tang H, Gallione CJ, et al. Sturge-weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368(21):1971–9. Accessed 20130523; 12/17/2015 5:54:01 PM. https://doi.org/10.1056/NEJMoa1213507.
To assist the reader in gaining familiarity with available evidence, the following rating system has been used to indicate key references for each chapter’s content:
***: Critical material. Anyone dealing with this condition should be familiar with this reference.
**: Useful material. Important information that is valuable in in clinical or scientific practice related to this condition.
*: Optional material. For readers with a strong interest in the chapter content or a desire to study it in greater depth.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Perkins, J.A., Bennett, J.T., Dobyns, W. (2018). Molecular Genetics and Vascular Anomalies. In: Perkins, J., Balakrishnan, K. (eds) Evidence-Based Management of Head and Neck Vascular Anomalies. Springer, Cham. https://doi.org/10.1007/978-3-319-92306-2_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-92306-2_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-92305-5
Online ISBN: 978-3-319-92306-2
eBook Packages: MedicineMedicine (R0)