Abstract
The genetic basis of many dermatologic diseases is becoming increasingly apparent however its clinical application to an individual patient remains a challenge. This chapter aims to highlight the utility of genetic testing in the setting of screening, diagnosing and counseling patients. Gardner’s syndrome, Peutz-Jeghers syndrome, Cowden syndrome, MEN Syndromes, Ataxia Telangiectasia, Wiskott-Aldrich syndrome, Familial Mediterranean Fever are highlighted as examples of diseases with cutaneous findings where genetic knowledge can help guide clinical care.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ferris FFM. Ferri’s clinical advisor 2015: 5 books in 1. 1st ed. Philadelphia: Elsevier; 2015.
Bisgaard ML, Bulow S. Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts. Am J Med Genet A. 2006;140(3):200–4.
Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006;101(2):385–98.
Syngal S, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62; quiz 263.
Vasen HF, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008;57(5):704–13.
Bjork JA, et al. Risk factors for rectal cancer morbidity and mortality in patients with familial adenomatous polyposis after colectomy and ileorectal anastomosis. Dis Colon Rectum. 2000;43(12):1719–25.
Bulow S. Results of national registration of familial adenomatous polyposis. Gut. 2003;52(5):742–6.
Heiskanen I, Luostarinen T, Jarvinen HJ. Impact of screening examinations on survival in familial adenomatous polyposis. Scand J Gastroenterol. 2000;35(12):1284–7.
Parc YR, et al. Familial adenomatous polyposis: prevalence of adenomas in the ileal pouch after restorative proctocolectomy. Ann Surg. 2001;233(3):360–4.
Groves CJ, et al. Prevalence and morphology of pouch and ileal adenomas in familial adenomatous polyposis. Dis Colon Rectum. 2005;48(4):816–23.
Friederich P, et al. Risk of developing adenomas and carcinomas in the ileal pouch in patients with familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2008;6(11):1237–42.
Tajika M, et al. Prevalence of adenomas and carcinomas in the ileal pouch after proctocolectomy in patients with familial adenomatous polyposis. J Gastrointest Surg. 2009;13(7):1266–73.
Campos FG, et al. Rectal and pouch recurrences after surgical treatment for familial adenomatous polyposis. J Gastrointest Surg. 2009;13(1):129–36.
Ooi BS, et al. Anal transitional zone cancer after restorative proctocolectomy and ileoanal anastomosis in familial adenomatous polyposis: report of two cases. Dis Colon Rectum. 2003;46(10):1418–23; discussion 1422–3.
Tulchinsky H, et al. Extracolonic manifestations of familial adenomatous polyposis after proctocolectomy. Arch Surg. 2005;140(2):159–63; discussion 164.
Church J. Ileoanal pouch neoplasia in familial adenomatous polyposis: an underestimated threat. Dis Colon Rectum. 2005;48(9):1708–13.
NCCN clinical practice guidelines. 3 May 2015.
Herraiz M, et al. Prevalence of thyroid cancer in familial adenomatous polyposis syndrome and the role of screening ultrasound examinations. Clin Gastroenterol Hepatol. 2007;5(3):367–73.
Giardiello FM, et al. Hepatoblastoma and APC gene mutation in familial adenomatous polyposis. Gut. 1996;39(6):867–9.
van Lier MG, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105(6):1258–64; author reply 1265.
Lim W, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004;126(7):1788–94.
van Lier MG, et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut. 2011;60(2):141–7.
Resta N, et al. Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study. Dig Liver Dis. 2013;45(7):606–11.
Giardiello FM, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119(6):1447–53.
Utsunomiya J, et al. Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J. 1975;136(2):71–82.
Jewel Samadder N, Kory M, Jasperson W. In: Intestinal Polyposis Syndromes. Switzerland: Springer International Publishing; 2015.
Hinds R, et al. Complications of childhood Peutz-Jeghers syndrome: implications for pediatric screening. J Pediatr Gastroenterol Nutr. 2004;39(2):219–20.
van Lier MG, et al. High cumulative risk of intussusception in patients with Peutz-Jeghers syndrome: time to update surveillance guidelines? Am J Gastroenterol. 2011;106(5):940–5.
Cunningham JD, et al. The role of laparoscopy in the management of intussusception in the Peutz-Jeghers syndrome: case report and review of the literature. Surg Laparosc Endosc. 1998;8(1):17–20.
Lebwohl M. Peutz-Jeghers syndrome. In: Treatment of skin disease comprehensive therapeutic strategies. Philadelphia: Elsevier; 2014.
Hernan I, et al. De novo germline mutation in the serine-threonine kinase STK11/LKB1 gene associated with Peutz-Jeghers syndrome. Clin Genet. 2004;66(1):58–62.
Beggs AD, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59(7):975–86.
Mallory SB. Cowden syndrome (multiple hamartoma syndrome). Dermatol Clin. 1995;13(1):27–31.
Monga E, et al. Multiple hamartoma syndrome: clinicoradiological evaluation and histopathological correlation with brief review of literature. Indian J Dermatol. 2014;59(6):598–601.
Marra G, et al. Cowden's disease with extensive gastrointestinal polyposis. J Clin Gastroenterol. 1994;18(1):42–7.
Starink TM, et al. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet. 1986;29(3):222–33.
Brownstein MH, Wolf M, Bikowski JB. Cowden's disease: a cutaneous marker of breast cancer. Cancer. 1978;41(6):2393–8.
Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet. 2000;37(11):828–30.
Schreibman IR, et al. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol. 2005;100(2):476–90.
Nelen MR, et al. Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet. 1999;7(3):267–73.
Melbarde-Gorkusa I, et al. Challenges in the management of a patient with Cowden syndrome: case report and literature review. Hered Cancer Clin Pract. 2012;10:5.
Hammami S, et al. Managing the risk of cancer in Cowden syndrome: a case report. J Med Case Rep. 2012;6:225.
Tan MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400–7.
Thakker RV. Multiple endrocrine neoplasia type I. In: Jameson J, De Groot L, editor. Endocrinology. Philadelphia: Elseivier; 2010. p. 2719–41.
Machens A, et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol (Oxf). 2007;67(4):613–22.
Kann PH, et al. Natural course of small, asymptomatic neuroendocrine pancreatic tumours in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study. Endocr Relat Cancer. 2006;13(4):1195–202.
Newey PJ, et al. Asymptomatic children with multiple endocrine neoplasia type 1 mutations may harbor nonfunctioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2009;94(10):3640–6.
Brandi ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–71.
Thomas-Marques L, et al. Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol. 2006;101(2):266–73.
Gibril F, et al. Prospective study of the natural history of gastrinoma in patients with MEN1: definition of an aggressive and a nonaggressive form. J Clin Endocrinol Metab. 2001;86(11):5282–93.
Thakker RV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011.
Trouillas J, et al. Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol. 2008;32(4):534–43.
Verges B, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87(2):457–65.
Sakurai A, et al. Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a multicentre database. Clin Endocrinol (Oxf). 2012;76(4):533–9.
Asgharian B, et al. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res. 2004;10(3):869–80.
Degroot LJ, Jameson JL. 148 multiple endrocrine neoplasia type I. In: Endocrinology: adult and pediatric. Philadelphia: Saunders/Elsevier; 2010.
Marini F, Giusti F, Brandi ML. Genetic test in multiple endocrine neoplasia type 1 syndrome: an evolving story. World J Exp Med. 2015;5(2):124–9.
Howe JR, Norton JA, Wells Jr SA. Prevalence of pheochromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: results of long-term follow-up. Surgery. 1993;114(6):1070–7.
Eng C, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996;276(19):1575–9.
Lairmore TC, et al. Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes. Ann Surg. 1993;217(6):595–601; discussion 601–3.
Wray CJ, et al. Failure to recognize multiple endocrine neoplasia 2B: more common than we think? Ann Surg Oncol. 2008;15(1):293–301.
Brauckhoff M, et al. Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B: An exploratory analysis. Surgery. 2008;144(6):1044–50; discussion 1050–3.
Lodish M. Multiple endocrine neoplasia type 2. Front Horm Res. 2013;41:16–29.
Moline J, Eng C. Multiple endocrine neoplasia type 2: an overview. Genet Med. 2011;13(9):755–64.
Skinner MA, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353(11):1105–13.
Chen H, et al. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010;39(6):775–83.
Kloos RT, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612.
McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004;5(8):772–6.
Woods CG, Taylor AM. Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals. Q J Med. 1992;82(298):169–79.
Crawford TO. Ataxia telangiectasia. Semin Pediatr Neurol. 1998;5(4):287–94.
Gatti RA, et al. The pathogenesis of ataxia-telangiectasia. Learning from a Rosetta Stone. Clin Rev Allergy Immunol. 2001;20(1):87–108.
Sedgwick RP, Boder E. Ataxia-Telangiectasia. In: Handbook of clinical neurology. Philadelphia: Elsevier Publishing; Vol. 60. 1991. p. 347–423.
Lewis RF, Lederman HM, Crawford TO. Ocular motor abnormalities in ataxia telangiectasia. Ann Neurol. 1999;46(3):287–95.
Baloh RW, Yee RD, Boder E. Eye movements in ataxia-telangiectasia. Neurology. 1978;28(11):1099–104.
Gumy-Pause F, Wacker P, Sappino AP. ATM gene and lymphoid malignancies. Leukemia. 2004;18(2):238–42.
Angele S, et al. ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity. Cancer Res. 2003;63(24):8717–25.
Thorstenson YR, et al. Contributions of ATM mutations to familial breast and ovarian cancer. Cancer Res. 2003;63(12):3325–33.
Ambrose M, Gatti RA. Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions. Blood. 2013;121(20):4036–45.
Khanna KK, et al. ATM associates with and phosphorylates p53: mapping the region of interaction. Nat Genet. 1998;20(4):398–400.
Swift M, et al. The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet. 1986;39(5):573–83.
Swift M, et al. Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med. 1987;316(21):1289–94.
Massaad MJ, Ramesh N, Geha RS. Wiskott-Aldrich syndrome: a comprehensive review. Ann N Y Acad Sci. 2013;1285:26–43.
Sullivan KE, et al. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. 1994;125(6 Pt 1):876–85.
Loyola Presa JG, et al. Cutaneous manifestations in patients with Wiskott-Aldrich syndrome submitted to haematopoietic stem cell transplantation. Arch Dis Child. 2013;98(4):304–7.
Modell V, et al. Global study of primary immunodeficiency diseases (PI)–diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. Immunol Res. 2011;51(1):61–70.
Litzman J, et al. Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome. Arch Dis Child. 1996;75(5):436–9.
Buchbinder D, Nugent DJ, Fillipovich AH. Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments. Appl Clin Genet. 2014;7:55–66.
Mahlaoui N, et al. Characteristics and outcome of early-onset, severe forms of Wiskott-Aldrich syndrome. Blood. 2013;121(9):1510–6.
Ozsahin H, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood. 2008;111(1):439–45.
Antoine C, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. Lancet. 2003;361(9357):553–60.
Gungor T, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383(9915):436–48.
Shohat M, Halpern GJ. Familial Mediterranean fever–a review. Genet Med. 2011;13(6):487–98.
Kucuk A, et al. Familial Mediterranean fever. Acta Medica (Hradec Kralove). 2014;57(3):97–104.
Lidar M, et al. The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever. J Rheumatol. 2006;33(6):1089–92.
Tunca M, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84(1):1–11.
El-Shanti H, Majeed HA, El-Khateeb M. Familial mediterranean fever in Arabs. Lancet. 2006;367(9515):1016–24.
A candidate gene for familial Mediterranean fever. Nat Genet. 1997;17(1):25–31.
Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell. 1997;90(4):797–807.
Giancane G, et al. Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis. 2015;74(4):635–41.
Stoffels M, et al. MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease. Ann Rheum Dis. 2014;73(2):455–61.
Ben-Chetrit E, Touitou I. Familial mediterranean Fever in the world. Arthritis Rheum. 2009;61(10):1447–53.
Onen F. Familial Mediterranean fever. Rheumatol Int. 2006;26(6):489–96.
Hentgen V, et al. Evidence-based recommendations for the practical management of Familial Mediterranean fever. Semin Arthritis Rheum. 2013;43(3):387–91.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Thiede, R., Butler, D. (2016). Genetic Testing and Personalized Medicine in Dermatology. In: Norman, R. (eds) Personalized, Evolutionary, and Ecological Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-41088-3_1
Download citation
DOI: https://doi.org/10.1007/978-3-319-41088-3_1
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-41086-9
Online ISBN: 978-3-319-41088-3
eBook Packages: MedicineMedicine (R0)