Abstract
Carney complex is a rare disease inherited in an autosomal dominant manner. It is mostly caused by inactivating mutations of the subunit of protein kinase A. Carney complex is associated with atrial myxoma, nevi or myxomas of the skin, breast tumor and endocrine overactivity. Primary pigmented nodular adrenocortical disease is the specific endocrine manifestation. The authors present the history of a 53-year-old female patient who had undergone surgery for atrial myxomas, thyroid tumor and breast cancer. She was also operated for an adrenal adenoma causing Cushing’s syndrome. Genetic study revealed a novel mutation in the regulatory subunit of protein kinase A (ivs2-1G>A splice mutation in intron 2). Her heterozygous twins were also genetically screened and one of them carried the same mutation. The authors emphasize that despite the absence of specific treatment for patients with Carney complex, confirmation of the diagnosis by genetic studies is important for the close follow-up of the patient and early identification of novel manifestations.
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References
Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL (1985) The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 64(4):270–283
Stratakis CA, Kirschner LS, Carney JA (2001) Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 86(9):4041–4046
Stratakis CA, Kirschner LS, Carney JA (1998) Carney complex: diagnosis and management of the complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas. Am J Med Genet 80(2):183–185
Stratakis CA, Horvath A (1993–2003 Feb 05) Carney Complex. In: Pagon RA BT, Dolan CR, Stephens K (ed) GeneReviews [Internet]. Seattle (WA). http://www.ncbi.nlm.nih.gov/books/NBK1286/. Last update date:2010 Jun 22.
Carney JA, Stratakis CA (1998) Epithelioid blue nevus and psammomatous melanotic schwannoma: the unusual pigmented skin tumors of the Carney complex. Semin Diagn Pathol 15(3):216–224
Bertherat J (2006) Carney complex (CNC). Orphanet J Rare Dis 1:21
Libe R, Horvath A, Vezzosi D, Fratticci A, Coste J, Perlemoine K, Ragazzon B, Guillaud-Bataille M, Groussin L, Clauser E, Raffin-Sanson ML, Siegel J, Moran J, Drori-Herishanu L, Faucz FR, Lodish M, Nesterova M, Bertagna X, Bertherat J, Stratakis CA (2011) Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype. J Clin Endocrinol Metab 96(1):E208–E214
Vezzosi D, Vignaux O, Dupin N, Bertherat J (2010) Carney complex: clinical and genetic 2010 update. Ann Endocrinol (Paris) 71(6):486–493
Rothenbuhler A, Stratakis CA (2010) Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metab 24(3):389–399
Horvath A, Bertherat J, Groussin L, Guillaud-Bataille M, Tsang K, Cazabat L, Libe R, Remmers E, Rene-Corail F, Faucz FR, Clauser E, Calender A, Bertagna X, Carney JA, Stratakis CA (2010) Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Hum Mutat 31(4):369–379
Pan L, Peng L, Jean-Gilles J, Zhang X, Wieczorek R, Jain S, Levine V, Osman I, Prieto VG, Lee P (2010) Novel PRKAR1A gene mutations in Carney Complex. Int J Clin Exp Pathol 3(5):545–548
Storr HL, Metherell LA, Dias R, Savage MO, Rasmussen AK, Clark AJ, Main KM (2010) Familial isolated primary pigmented nodular adrenocortical disease associated with a novel low penetrance PRKAR1A gene splice site mutation. Horm Res Paediatr 73(2):115–119
Landry CS, Waguespack SG, Perrier ND (2009) Surgical management of nonmultiple endocrine neoplasia endocrinopathies: state-of-the-art review. Surg Clin North Am 89(5):1069–1089
Szabo D, Zsippai A, Bendes M, Tombol Z, Szabo PM, Racz K, Igaz P (2010) Pathogenesis of adrenocortical cancer. Orv Hetil (Hungarian Medical Journal) 151(29):1163–1170 (In Hungarian)
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We thank members of our laboratory (Molecular Medicine Research Group) for scientific advice. We thank the patient and her family for contribution and co-operation.
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Halászlaki, C., Takács, I., Butz, H. et al. Novel Genetic Mutation in the Background of Carney Complex. Pathol. Oncol. Res. 18, 149–152 (2012). https://doi.org/10.1007/s12253-012-9502-3
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DOI: https://doi.org/10.1007/s12253-012-9502-3