A Review of Vascular Anomalies: Genetics and Common Syndromes

Abstract

Vascular tumors and malformations are unique in that affected cells exhibit disrupted angiogenesis. The current treatment options often yield suboptimal results. New insight into the genetics and molecular basis of vascular anomalies may pave the way for potential development of targeted therapy. The authors review the genetic and molecular basis of vascular anomalies and common associated syndromes.

Keywords

vascular tumors - vascular malformations - vascular anomalies - syndrome vascular anomalies - genetics

• References

• 1 Mulliken JB, Glowacki J. Classification of pediatric vascular lesions. Plast Reconstr Surg 1982; 70 (1) 120-121
• 2 Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg 1982; 69 (3) 412-422
• 3 Cohen Jr MM. Vascular update: morphogenesis, tumors, malformations, and molecular dimensions. Am J Med Genet A 2006; 140 (19) 2013-2038
• 4 Jinnin M, Medici D, Park L , et al. Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med 2008; 14 (11) 1236-1246
• 5 Boye E, Yu Y, Paranya G, Mulliken JB, Olsen BR, Bischoff J. Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 2001; 107 (6) 745-752
• 6 Chou A, Toon C, Pickett J , et al. Endocrine tumor syndromes and their genetics. Front Horm Res 2013; 41: 30-49
• 7 Chen F, Kishida T, Yao M , et al. Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype. Hum Mutat 1995; 5 (1) 66-75
• 8 Crossey PA, Foster K, Richards FM , et al. Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours. Hum Genet 1994; 93 (1) 53-58
• 9 Maranchie JK, Afonso A, Albert PS , et al. Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location. Hum Mutat 2004; 23 (1) 40-46
• 10 Kaplan RP, Wang JT, Amron DM, Kaplan L. Maffucci's syndrome: two case reports with a literature review. J Am Acad Dermatol 1993; 29 (5 Pt 2) 894-899
• 11 Lee NH, Choi EH, Choi WK, Lee SH, Ahn SK. Maffucci's syndrome with oral and intestinal haemangioma. Br J Dermatol 1999; 140 (5) 968-969
• 12 Halal F, Azouz EM. Generalized enchondromatosis in a boy with only platyspondyly in the father. Am J Med Genet 1991; 38 (4) 588-592
• 13 Pansuriya TC, van Eijk R, d'Adamo P , et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet 2011; 43 (12) 1256-1261
• 14 Duffy K. Genetics and syndromes associated with vascular malformations. Pediatr Clin North Am 2010; 57 (5) 1111-1120
• 15 Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol 1987; 16 (4) 899-906
• 16 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) 1971-1979
• 17 Van Raamsdonk CD, Fitch KR, Fuchs H, de Angelis MH, Barsh GS. Effects of G-protein mutations on skin color. Nat Genet 2004; 36 (9) 961-968
• 18 Kajio F, Nakazawa M. Vascular effects of endothelin-1 in stage 21 chick embryos. Heart Vessels 1997; 12 (6) 300-305
• 19 Vikkula M, Boon LM, Mulliken JB. Molecular genetics of vascular malformations. Matrix Biol 2001; 20 (5-6) 327-335
• 20 Moodley M, Ramdial P. Blue rubber bleb nevus syndrome: case report and review of the literature. Pediatrics 1993; 92 (1) 160-162
• 21 Jorizzo JR, Amparo EG. MR imaging of blue rubber bleb nevus syndrome. J Comput Assist Tomogr 1986; 10 (4) 686-688
• 22 Vikkula M, Boon LM, Carraway III KL , et al. Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell 1996; 87 (7) 1181-1190
• 23 Bean WB. Blue rubber bleb nevi of the skin and gastrointestinal tract. In: Vascular Spiders and Related Lesions of the Skin. Springfield, IL: Charles C. Thomas; 1958: 178-185
• 24 Kunishige M, Azuma H, Masuda K , et al. Interferon alpha-2a therapy for disseminated intravascular coagulation in a patient with blue rubber bleb nevus syndrome. A case report. Angiology 1997; 48 (3) 273-277
• 25 Waybright EA, Selhorst JB, Rosenblum WI, Suter CG. Blue rubber bleb nevus syndrome with CNS involvement and thrombosis of a vein of Galen malformation. Ann Neurol 1978; 3 (5) 464-467
• 26 McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med 2011; 13 (7) 607-616
• 27 Bossler AD, Richards J, George C, Godmilow L, Ganguly A. Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat 2006; 27 (7) 667-675
• 28 Berg J, Porteous M, Reinhardt D , et al. Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations. J Med Genet 2003; 40 (8) 585-590
• 29 Plauchu H, de Chadarévian JP, Bideau A, Robert JM. Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet 1989; 32 (3) 291-297
• 30 Porteous ME, Burn J, Proctor SJ. Hereditary haemorrhagic telangiectasia: a clinical analysis. J Med Genet 1992; 29 (8) 527-530
• 31 AAssar OS, Friedman CM, White Jr RI. The natural history of epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 1991; 101 (9) 977-980
• 32 Guttmacher AE, Marchuk DA, White Jr RI. Hereditary hemorrhagic telangiectasia. N Engl J Med 1995; 333 (14) 918-924
• 33 Vase P, Holm M, Arendrup H. Pulmonary arteriovenous fistulas in hereditary hemorrhagic telangiectasia. Acta Med Scand 1985; 218 (1) 105-109
• 34 Attisano L, Cárcamo J, Ventura F, Weis FM, Massagué J, Wrana JL. Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell 1993; 75 (4) 671-680
• 35 Barbara NP, Wrana JL, Letarte M. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily. J Biol Chem 1999; 274 (2) 584-594
• 36 Samuel M, Spitz L. Klippel-Trenaunay syndrome: clinical features, complications and management in children. Br J Surg 1995; 82 (6) 757-761
• 37 Happle R. Klippel-Trenaunay syndrome: is it a paradominant trait?. Br J Dermatol 1993; 128 (4) 465-466
• 38 Whelan AJ, Watson MS, Porter FD, Steiner RD. Klippel-Trenaunay-Weber syndrome associated with a 5:11 balanced translocation. Am J Med Genet 1995; 59 (4) 492-494
• 39 Tian XL, Kadaba R, You SA , et al. Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome. Nature 2004; 427 (6975) 640-645
• 40 Barker KT, Foulkes WD, Schwartz CE , et al. Is the E133K allele of VG5Q associated with Klippel-Trenaunay and other overgrowth syndromes?. J Med Genet 2006; 43 (7) 613-614
• 41 Gutierrez S, Magano L, Delicado A , et al. The G397A (E133K) change in the AGGF1 (VG5Q) gene is a single nucleotide polymorphism in the Spanish population. Am J Med Genet A 2006; 140 (24) 2832-2833
• 42 Eerola I, Boon LM, Mulliken JB , et al. Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am J Hum Genet 2003; 73 (6) 1240-1249
• 43 Turner JT, Cohen Jr MM, Biesecker LG. Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. Am J Med Genet A 2004; 130A (2) 111-122
• 44 Wiedemann HR, Burgio GR, Aldenhoff P, Kunze J, Kaufmann HJ, Schirg E. The proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 1983; 140 (1) 5-12
• 45 Viljoen DL, Saxe N, Temple-Camp C. Cutaneous manifestations of the Proteus syndrome. Pediatr Dermatol 1988; 5 (1) 14-21
• 46 Clark RD, Donnai D, Rogers J, Cooper J, Baraitser M. Proteus syndrome: an expanded phenotype. Am J Med Genet 1987; 27 (1) 99-117
• 47 Malamitsi-Puchner A, Dimitriadis D, Bartsocas C, Wiedemann HR. Proteus syndrome: course of a severe case. Am J Med Genet 1990; 35 (2) 283-285
• 48 Biesecker LG, Happle R, Mulliken JB , et al. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 1999; 84 (5) 389-395
• 49 Goodship J, Redfearn A, Milligan D, Gardner-Medwin D, Burn J. Transmission of Proteus syndrome from father to son?. J Med Genet 1991; 28 (11) 781-785
• 50 Brockmann K, Happle R, Oeffner F, König A. Monozygotic twins discordant for Proteus syndrome. Am J Med Genet A 2008; 146A (16) 2122-2125
• 51 Happle R. Cutaneous manifestation of lethal genes. Hum Genet 1986; 72 (3) 280
• 52 Lindhurst MJ, Sapp JC, Teer JK , et al. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med 2011; 365 (7) 611-619