- Department of Vascular Surgery, Fuwai Hospital, Beijing Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100037, P.R.China;
GUO Hongwei,
Email: ghwdr@sina.com
Carney complex (CNC) is a rare autosomal dominant syndrome, characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas and multiple endocrine tumors. The disease is caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22–24 coding for the regulatory subunit type Ⅰ alpha of protein kinase A (PKA) gene. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). We reviewed CNC’s clinical features, diagnosis, treatment and molecular etiology.
Citation： WEI Ke, GUO Hongwei. Clinical features and research progress of Carney complex. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(7): 627-632. doi: 10.7507/1007-4848.201712082 Copy
| 1. | Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab, 2001, 86(9): 4041-4046. |
| 2. | Sandrini F, Stratakis C. Clinical and molecular genetics of Carney complex. Mol Genet Metab, 2003. 78(2): 83-92. |
| 3. | Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore), 1985. 64(4): 270-283. |
| 4. | Atherton DJ, Pitcher DW, Wells RS, et al. A syndrome of various cutaneous pigmented lesions, myxoid neurofibromata and atrial myxoma: the NAME syndrome. Br J Dermatol, 1980, 103(4): 421-429. |
| 5. | Bain J. Carney's complex. Mayo Clin Proc, 1986. 61(6): 508. |
| 6. | Krieger LE. Jablonski's Dictionary of Syndromes and Eponymic Diseases. 2nd Edition. Yale J Biol Med, 1991, 64(5): 544. |
| 7. | Carney JA. The triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. Cancer, 1979, 43(1): 374-382. |
| 8. | Bertherat J, Horvath A, Groussin L, et al. Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab, 2009, 94(6): 2085-2091. |
| 9. | Espiard S, Bertherat J. Carney complex. Front Horm Res, 2013. 41: 50-62. |
| 10. | Boikos SA, Stratakis CA. Carney complex: the first 20 years. Curr Opin Oncol, 2007, 19(1): 24-29. |
| 11. | Zawadzki KM, Taylor SS. cAMP-dependent protein kinase regulatory subunit type Ⅱbeta: active site mutations define an isoform-specific network for allosteric signaling by cAMP. J Biol Chem, 2004, 279(8): 7029-7036. |
| 12. | Yu S, Maillard RA, Gribenko AV, et al. The N-terminal capping propensities of the D-helix modulate the allosteric activation of the Escherichia coli cAMP receptor protein. J Biol Chem, 2012, 287(47): 39402-39411. |
| 13. | Kirschner LS, Carney JA, Pack S, et al. Mutations of the gene encoding the protein kinase A type Ⅰ-alpha regulatory subunit in patients with the Carney complex. Nat Genet, 2000, 26(1): 89-92. |
| 14. | Groussin L, Horvath A, Jullian E, et al. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab, 2006, 91(5): 1943-1949. |
| 15. | Horvath A, Bossis I, Giatzakis C, et al. Large deletions of the PRKAR1A gene in Carney complex. Clin Cancer Res, 2008, 14(2): 388-395. |
| 16. | Horvath A, Bertherat J, Groussin L, et al. Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Hum Mutat, 2010, 31(4): 369-379. |
| 17. | Salpea P, Horvath A, London E, et al. Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab, 2014, 99(1): E183-E188. |
| 18. | Meoli E, Bossis I, Cazabat L, et al. Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors. Cancer Res, 2008, 68(9): 3133-3141. |
| 19. | Greene EL, Horvath AD, Nesterova M, et al. In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Hum Mutat, 2008. 29(5): 633-639. |
| 20. | Kirschner LS, Sandrini F, Monbo J, et al. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Hum Mol Genet, 2000, 9(20): 3037-3046. |
| 21. | Kirschner LS, Kusewitt DF, Matyakhina L, et al. A mouse model for the Carney complex tumor syndrome develops neoplasia in cyclic AMP-responsive tissues. Cancer Res, 2005, 65(11): 4506-4514. |
| 22. | Griffin KJ, Kirschner LS, Matyakhina L, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet, 2004, 41(12): 923-931. |
| 23. | Beuschlein F, Fassnacht M, Assié G, et al. Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. N Engl J Med, 2014, 370(11): 1019-1028. |
| 24. | Forlino A, Vetro A, Garavelli L, et al. PRKACB and Carney complex. N Engl J Med, 2014, 370(11): 1065-1067. |
| 25. | MatyakhinaL, Pack S, Kirschner LS, et al. Chromosome 2 (2p16) abnormalities in Carney complex tumours. J Med Genet, 2003, 40(4): 268-277. |
| 26. | Stratakis CA, Carney JA, Lin JP, et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest, 1996, 97(3): 699-705. |
| 27. | Carney JA, Stratakis CA. Epithelioid blue nevus and psammomatous melanotic schwannoma: the unusual pigmented skin tumors of the Carney complex. Semin Diagn Pathol, 1998, 15(3): 216-224. |
| 28. | Stratakis CA, Kirschner LS, Carney JA. Carney complex: diagnosis and management of the complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas. Am J Med Genet, 1998, 80(2): 183-185. |
| 29. | Stratakis CA. Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes. Front Biosci, 2000. 5: D353-D366. |
| 30. | Stratakis CA, Kirschner LS. Isolated familial somatotropinomas: does the disease map to 11q13 or to 2p16? J Clin Endocrinol Metab, 2000, 85(12): 4920-4921. |
| 31. | Mateus C, Palangié A, Franck N, , et al. Heterogeneity of skin manifestations in patients with Carney complex. J Am Acad Dermatol, 2008, 59(5): 801-810. |
| 32. | Rothenbuhler A, Stratakis CA. Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metab, 2010, 24(3): 389-399. |
| 33. | Courcoutsakis NA, Tatsi C, Patronas NJ, et al. The complex of myxomas, spotty skin pigmentation and endocrine overactivity (Carney complex): imaging findings with clinical and pathological correlation. Insights Imaging, 2013, 4(1): 119-133. |
| 34. | Stratakis CA, Salpea P, Raygada M. Carney Complex. Adam MP, Ardinger HH, Pagon RA, et al, eds. Gene Reviews. Seattle (WA):University of Washington, 1993. 1993-2018. |
| 35. | Mabuchi T, Shimizu M, Ino H, et al. PRKAR1A gene mutation in patients with cardiac myxoma. Int J Cardiol, 2005, 102(2): 273-277. |
| 36. | Lee B, Sir JJ, Park SW, et al. Right-sided myxomas with extramedullary hematopoiesis and ossification in Carney complex. Int J Cardiol, 2008, 130(2): e63-e65. |
| 37. | Bireta C, Popov AF, Schotola H, et al. Carney-Complex: multiple resections of recurrent cardiac myxoma. J Cardiothorac Surg, 2011, 6: 12. |
| 38. | Boikos SA, Stratakis CA. Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities. Pituitary, 2006, 9(3): 203-209. |
| 39. | Shenoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. Am J Surg Pathol, 1984, 8(5): 335-344. |
| 40. | Louiset E, Stratakis CA, Perraudin V, et al. The paradoxical increase in cortisol secretion induced by dexamethasone in primary pigmented nodular adrenocortical disease involves a glucocorticoid receptor-mediated effect of dexamethasone on protein kinase A catalytic subunits. J Clin Endocrinol Metab, 2009. 94(7): 2406-2413. |
| 41. | Stratakis CA, Kirschner LS. Clinical and genetic analysis of primary bilateral adrenal diseases (micro- and macronodular disease) leading to Cushing syndrome. Horm Metab Res, 1998. 30(6-7): 456-463. |
| 42. | Bertherat J. Adrenocortical cancer in Carney complex: a paradigm of endocrine tumor progression or an association of genetic predisposing factors? J Clin Endocrinol Metab, 2012, 97(2): 387-390. |
| 43. | Pringle DR, Yin Z, Lee AA, et al. Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer. Endocr Relat Cancer, 2012, 19(3): 435-446. |
| 44. | Carney JA. Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol, 1990, 14(3): 206-222. |
| 45. | Utiger CA1, Headington JT. Psammomatous melanotic schwannoma. A new cutaneous marker for Carney's complex. Arch Dermatol, 1993, 129(2): 202-204. |
| 46. | Rodriguez FJ, Stratakis CA, Evans DG. Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes. Acta Neuropathol, 2012, 123(3): 349-367. |
| 47. | Wilkes D, McDermott DA, Basson CT. McDermott and C.T. Basson, Clinical phenotypes and molecular genetic mechanisms of Carney complex. Lancet Oncol, 2005, 6(7): 501-508. |
| 48. | Hachisuka J, Ichikawa M, Moroi Y, et al. A case of Carney complex. Int J Dermatol, 2006. 45(12): 1406-1407. |
| 49. | Brown B, Ram A, Clayton P, et al. Conservative management of bilateral Sertoli cell tumors of the testicle in association with the Carney complex: a case report. J Pediatr Surg, 2007, 42(9): E13-E15. |
| 50. | Vandersteen A, Turnbull J, Jan W, et al. Cutaneous signs are important in the diagnosis of the rare neoplasia syndrome Carney complex. Eur J Pediatr, 2009, 168(11): 1401-1404. |
| 51. | Stratakis CA, Papageorgiou T, Premkumar A, et al. Ovarian lesions in Carney complex: clinical genetics and possible predisposition to malignancy. J Clin Endocrinol Metab, 2000, 85(11): 4359-4366. |
| 52. | Barlow JF, Abu-Gazeleh S, Tam GE, et al. Myxoid tumor of the uterus and right atrial myxomas. S D J Med, 1983, 36(7): 9-13. |
| 53. | Gennari M, Stratakis CA, Hovarth A, et al. A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations. Clin Endocrinol (Oxf), 2008, 69(5): 751-755. |
| 54. | Gaujoux S, Tissier F, Ragazzon B, et al. Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association. J Clin Endocrinol Metab, 2011. 96(11): E1888-E1895. |
| 55. | Mateus C, Palangié A, Franck N, et al. Heterogeneity of skin manifestations in patients with Carney complex. J Am Acad Dermatol, 2008, 59(5): 801-810. |
| 56. | Bossis I, Voutetakis A, Bei T, et al. Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer, 2004, 11(2): 265-280. |
| 57. | McCarthy PM, Piehler JM, Schaff HV, et al. The significance of multiple, recurrent, and " complex” cardiac myxomas. J Thorac Cardiovasc Surg, 1986, 91(3): 389-396. |
| 58. | Carney JA. Carney complex: the complex of myxomas, spotty pigmentation, endocrine overactivity, and schwannomas. Semin Dermatol, 1995, 14(2): 90-98. |
| 59. | Watson JC, Stratakis CA, Bryant-Greenwood PK, et al. Neurosurgical implications of Carney complex. J Neurosurg, 2000, 92(3): 413-418. |
| 60. | Cignarelli M, Picca G, Campo M, et al. A six month mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney complex. J Endocrinol Invest, 2005, 28(1): 54-60. |
| 61. | Horvath A, Boikos S, Giatzakis C, et al. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet, 2006, 38(7): 794-800. |
| 62. | Salpea P, Horvath A, London E, et al. Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab, 2014, 99(1): E183-E188. |
| 63. | Fogt F, Zimmerman RL, Hartmann CJ, et al. Genetic alterations of Carney complex are not present in sporadic cardiac myxomas. Int J Mol Med, 2002, 9(1): 59-60. |
| 64. | Imai Y, Taketani T, Maemura K, et al. Genetic analysis in a patient with recurrent cardiac myxoma and endocrinopathy. Circ J, 2005, 69(8): 994-995. |
| 65. | Stergiopoulos SG, Stratakis CA. Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease! FEBS Lett, 2003, 546(1): 59-64. |
| 66. | Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol, 2010. 28(5): 893-901. |
- 1. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab, 2001, 86(9): 4041-4046.
- 2. Sandrini F, Stratakis C. Clinical and molecular genetics of Carney complex. Mol Genet Metab, 2003. 78(2): 83-92.
- 3. Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore), 1985. 64(4): 270-283.
- 4. Atherton DJ, Pitcher DW, Wells RS, et al. A syndrome of various cutaneous pigmented lesions, myxoid neurofibromata and atrial myxoma: the NAME syndrome. Br J Dermatol, 1980, 103(4): 421-429.
- 5. Bain J. Carney's complex. Mayo Clin Proc, 1986. 61(6): 508.
- 6. Krieger LE. Jablonski's Dictionary of Syndromes and Eponymic Diseases. 2nd Edition. Yale J Biol Med, 1991, 64(5): 544.
- 7. Carney JA. The triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. Cancer, 1979, 43(1): 374-382.
- 8. Bertherat J, Horvath A, Groussin L, et al. Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab, 2009, 94(6): 2085-2091.
- 9. Espiard S, Bertherat J. Carney complex. Front Horm Res, 2013. 41: 50-62.
- 10. Boikos SA, Stratakis CA. Carney complex: the first 20 years. Curr Opin Oncol, 2007, 19(1): 24-29.
- 11. Zawadzki KM, Taylor SS. cAMP-dependent protein kinase regulatory subunit type Ⅱbeta: active site mutations define an isoform-specific network for allosteric signaling by cAMP. J Biol Chem, 2004, 279(8): 7029-7036.
- 12. Yu S, Maillard RA, Gribenko AV, et al. The N-terminal capping propensities of the D-helix modulate the allosteric activation of the Escherichia coli cAMP receptor protein. J Biol Chem, 2012, 287(47): 39402-39411.
- 13. Kirschner LS, Carney JA, Pack S, et al. Mutations of the gene encoding the protein kinase A type Ⅰ-alpha regulatory subunit in patients with the Carney complex. Nat Genet, 2000, 26(1): 89-92.
- 14. Groussin L, Horvath A, Jullian E, et al. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab, 2006, 91(5): 1943-1949.
- 15. Horvath A, Bossis I, Giatzakis C, et al. Large deletions of the PRKAR1A gene in Carney complex. Clin Cancer Res, 2008, 14(2): 388-395.
- 16. Horvath A, Bertherat J, Groussin L, et al. Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Hum Mutat, 2010, 31(4): 369-379.
- 17. Salpea P, Horvath A, London E, et al. Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab, 2014, 99(1): E183-E188.
- 18. Meoli E, Bossis I, Cazabat L, et al. Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors. Cancer Res, 2008, 68(9): 3133-3141.
- 19. Greene EL, Horvath AD, Nesterova M, et al. In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Hum Mutat, 2008. 29(5): 633-639.
- 20. Kirschner LS, Sandrini F, Monbo J, et al. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Hum Mol Genet, 2000, 9(20): 3037-3046.
- 21. Kirschner LS, Kusewitt DF, Matyakhina L, et al. A mouse model for the Carney complex tumor syndrome develops neoplasia in cyclic AMP-responsive tissues. Cancer Res, 2005, 65(11): 4506-4514.
- 22. Griffin KJ, Kirschner LS, Matyakhina L, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet, 2004, 41(12): 923-931.
- 23. Beuschlein F, Fassnacht M, Assié G, et al. Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. N Engl J Med, 2014, 370(11): 1019-1028.
- 24. Forlino A, Vetro A, Garavelli L, et al. PRKACB and Carney complex. N Engl J Med, 2014, 370(11): 1065-1067.
- 25. MatyakhinaL, Pack S, Kirschner LS, et al. Chromosome 2 (2p16) abnormalities in Carney complex tumours. J Med Genet, 2003, 40(4): 268-277.
- 26. Stratakis CA, Carney JA, Lin JP, et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest, 1996, 97(3): 699-705.
- 27. Carney JA, Stratakis CA. Epithelioid blue nevus and psammomatous melanotic schwannoma: the unusual pigmented skin tumors of the Carney complex. Semin Diagn Pathol, 1998, 15(3): 216-224.
- 28. Stratakis CA, Kirschner LS, Carney JA. Carney complex: diagnosis and management of the complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas. Am J Med Genet, 1998, 80(2): 183-185.
- 29. Stratakis CA. Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes. Front Biosci, 2000. 5: D353-D366.
- 30. Stratakis CA, Kirschner LS. Isolated familial somatotropinomas: does the disease map to 11q13 or to 2p16? J Clin Endocrinol Metab, 2000, 85(12): 4920-4921.
- 31. Mateus C, Palangié A, Franck N, , et al. Heterogeneity of skin manifestations in patients with Carney complex. J Am Acad Dermatol, 2008, 59(5): 801-810.
- 32. Rothenbuhler A, Stratakis CA. Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metab, 2010, 24(3): 389-399.
- 33. Courcoutsakis NA, Tatsi C, Patronas NJ, et al. The complex of myxomas, spotty skin pigmentation and endocrine overactivity (Carney complex): imaging findings with clinical and pathological correlation. Insights Imaging, 2013, 4(1): 119-133.
- 34. Stratakis CA, Salpea P, Raygada M. Carney Complex. Adam MP, Ardinger HH, Pagon RA, et al, eds. Gene Reviews. Seattle (WA):University of Washington, 1993. 1993-2018.
- 35. Mabuchi T, Shimizu M, Ino H, et al. PRKAR1A gene mutation in patients with cardiac myxoma. Int J Cardiol, 2005, 102(2): 273-277.
- 36. Lee B, Sir JJ, Park SW, et al. Right-sided myxomas with extramedullary hematopoiesis and ossification in Carney complex. Int J Cardiol, 2008, 130(2): e63-e65.
- 37. Bireta C, Popov AF, Schotola H, et al. Carney-Complex: multiple resections of recurrent cardiac myxoma. J Cardiothorac Surg, 2011, 6: 12.
- 38. Boikos SA, Stratakis CA. Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities. Pituitary, 2006, 9(3): 203-209.
- 39. Shenoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. Am J Surg Pathol, 1984, 8(5): 335-344.
- 40. Louiset E, Stratakis CA, Perraudin V, et al. The paradoxical increase in cortisol secretion induced by dexamethasone in primary pigmented nodular adrenocortical disease involves a glucocorticoid receptor-mediated effect of dexamethasone on protein kinase A catalytic subunits. J Clin Endocrinol Metab, 2009. 94(7): 2406-2413.
- 41. Stratakis CA, Kirschner LS. Clinical and genetic analysis of primary bilateral adrenal diseases (micro- and macronodular disease) leading to Cushing syndrome. Horm Metab Res, 1998. 30(6-7): 456-463.
- 42. Bertherat J. Adrenocortical cancer in Carney complex: a paradigm of endocrine tumor progression or an association of genetic predisposing factors? J Clin Endocrinol Metab, 2012, 97(2): 387-390.
- 43. Pringle DR, Yin Z, Lee AA, et al. Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer. Endocr Relat Cancer, 2012, 19(3): 435-446.
- 44. Carney JA. Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol, 1990, 14(3): 206-222.
- 45. Utiger CA1, Headington JT. Psammomatous melanotic schwannoma. A new cutaneous marker for Carney's complex. Arch Dermatol, 1993, 129(2): 202-204.
- 46. Rodriguez FJ, Stratakis CA, Evans DG. Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes. Acta Neuropathol, 2012, 123(3): 349-367.
- 47. Wilkes D, McDermott DA, Basson CT. McDermott and C.T. Basson, Clinical phenotypes and molecular genetic mechanisms of Carney complex. Lancet Oncol, 2005, 6(7): 501-508.
- 48. Hachisuka J, Ichikawa M, Moroi Y, et al. A case of Carney complex. Int J Dermatol, 2006. 45(12): 1406-1407.
- 49. Brown B, Ram A, Clayton P, et al. Conservative management of bilateral Sertoli cell tumors of the testicle in association with the Carney complex: a case report. J Pediatr Surg, 2007, 42(9): E13-E15.
- 50. Vandersteen A, Turnbull J, Jan W, et al. Cutaneous signs are important in the diagnosis of the rare neoplasia syndrome Carney complex. Eur J Pediatr, 2009, 168(11): 1401-1404.
- 51. Stratakis CA, Papageorgiou T, Premkumar A, et al. Ovarian lesions in Carney complex: clinical genetics and possible predisposition to malignancy. J Clin Endocrinol Metab, 2000, 85(11): 4359-4366.
- 52. Barlow JF, Abu-Gazeleh S, Tam GE, et al. Myxoid tumor of the uterus and right atrial myxomas. S D J Med, 1983, 36(7): 9-13.
- 53. Gennari M, Stratakis CA, Hovarth A, et al. A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations. Clin Endocrinol (Oxf), 2008, 69(5): 751-755.
- 54. Gaujoux S, Tissier F, Ragazzon B, et al. Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association. J Clin Endocrinol Metab, 2011. 96(11): E1888-E1895.
- 55. Mateus C, Palangié A, Franck N, et al. Heterogeneity of skin manifestations in patients with Carney complex. J Am Acad Dermatol, 2008, 59(5): 801-810.
- 56. Bossis I, Voutetakis A, Bei T, et al. Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer, 2004, 11(2): 265-280.
- 57. McCarthy PM, Piehler JM, Schaff HV, et al. The significance of multiple, recurrent, and " complex” cardiac myxomas. J Thorac Cardiovasc Surg, 1986, 91(3): 389-396.
- 58. Carney JA. Carney complex: the complex of myxomas, spotty pigmentation, endocrine overactivity, and schwannomas. Semin Dermatol, 1995, 14(2): 90-98.
- 59. Watson JC, Stratakis CA, Bryant-Greenwood PK, et al. Neurosurgical implications of Carney complex. J Neurosurg, 2000, 92(3): 413-418.
- 60. Cignarelli M, Picca G, Campo M, et al. A six month mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney complex. J Endocrinol Invest, 2005, 28(1): 54-60.
- 61. Horvath A, Boikos S, Giatzakis C, et al. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet, 2006, 38(7): 794-800.
- 62. Salpea P, Horvath A, London E, et al. Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab, 2014, 99(1): E183-E188.
- 63. Fogt F, Zimmerman RL, Hartmann CJ, et al. Genetic alterations of Carney complex are not present in sporadic cardiac myxomas. Int J Mol Med, 2002, 9(1): 59-60.
- 64. Imai Y, Taketani T, Maemura K, et al. Genetic analysis in a patient with recurrent cardiac myxoma and endocrinopathy. Circ J, 2005, 69(8): 994-995.
- 65. Stergiopoulos SG, Stratakis CA. Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease! FEBS Lett, 2003, 546(1): 59-64.
- 66. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol, 2010. 28(5): 893-901.