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Carney complex(CAR)

MedGen UID:
140810
Concept ID:
C0406810
Disease or Syndrome
Synonyms: Carney syndrome; Myxoma, spotty pigmentation, and endocrine overactivity
SNOMED CT: Carney complex (733491005); Carney syndrome (733491005); Myxoma, spotty pigmentation, endocrine overactivity syndrome (733491005); LAMB (lentigines, atrial myxoma, blue nevi) syndrome (733491005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related gene: PRKAR1A
 
Monarch Initiative: MONDO:0015285
OMIM®: 160980; 188830
Orphanet: ORPHA1359

Disease characteristics

Excerpted from the GeneReview: Carney Complex
Carney complex (CNC) is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of CNC and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and can manifest as intracardiac obstruction of blood flow, embolic phenomenon, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease (PPNAD), which causes Cushing syndrome, is the most frequently observed endocrine tumor in CNC, occurring in approximately 25% of affected individuals. Large cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one third of affected males within the first decade and in most adult males. Up to 75% of individuals with CNC have multiple thyroid nodules, most of which are nonfunctioning thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. The median age of diagnosis is 20 years. [from GeneReviews]
Authors:
Constantine A Stratakis   view full author information

Additional descriptions

From OMIM
Carney complex is an autosomal dominant multiple neoplasia syndrome characterized by cardiac, endocrine, cutaneous, and neural myxomatous tumors, as well as a variety of pigmented lesions of the skin and mucosae. Carney complex may simultaneously involve multiple endocrine glands, similar to classic MEN syndromes (MEN1; 131100 and MEN2; 171400). Carney complex shows some similarities to McCune-Albright syndrome (MAS; 174800), a sporadic condition that is also characterized by multiple endocrine and nonendocrine tumors, and shares skin abnormalities and some nonendocrine tumors with the lentiginoses and certain of the hamartomatoses, particularly Peutz-Jeghers syndrome (PJS; 175200). Carney complex is often associated with the unusual large-cell calcifying Sertoli cell tumor and psammomatous melanotic schwannomas (Kirschner et al., 2000; Stratakis et al., 2001). Genetic Heterogeneity of Carney Complex Carney complex type 2 (CNC2; 605244) has been mapped to chromosome 2p16, indicating genetic heterogeneity. See also isolated primary pigmented nodular adrenocortical disease (PPNAD1; 610489) and isolated cardiac myxoma (255960), both of which are manifestations of the Carney complex that can be seen in isolation. A family with features of the Carney complex and distal arthrogryposis (608837) associated with a mutation in the MYH8 gene (160741) has also been reported.  http://www.omim.org/entry/160980
From MedlinePlus Genetics
Carney complex is a disorder characterized by an increased risk of several types of tumors. Affected individuals also usually have changes in skin coloring (pigmentation). Signs and symptoms of this condition commonly begin in the teens or early adulthood.

Individuals with Carney complex are at increased risk of developing noncancerous (benign) tumors called myxomas in the heart (cardiac myxoma) and other parts of the body. Cardiac myxomas may be found in any of the four chambers of the heart and can develop in more than one chamber. These tumors can block the flow of blood through the heart, causing serious complications or sudden death. Myxomas may also develop on the skin and in internal organs. Skin myxomas appear as small bumps on the surface of the skin or as lumps underneath the skin. In Carney complex, myxomas have a tendency to recur after they are removed.

Individuals with Carney complex also develop tumors in hormone-producing (endocrine) glands, such as the adrenal glands located on top of each kidney. People with this condition may develop a specific type of adrenal disease called primary pigmented nodular adrenocortical disease (PPNAD). PPNAD causes the adrenal glands to produce an excess of the hormone cortisol. High levels of cortisol (hypercortisolism) can lead to the development of Cushing syndrome. This syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems.

People with Carney complex may also develop tumors of other endocrine tissues, including the thyroid, testes, and ovaries. A tumor called an adenoma may form in the pituitary gland, which is located at the base of the brain. A pituitary adenoma usually results in the production of too much growth hormone. Excess growth hormone leads to acromegaly, a condition characterized by large hands and feet, arthritis, and "coarse" facial features.

Almost all people with Carney complex have areas of unusual skin pigmentation. Brown skin spots called lentigines may appear anywhere on the body but tend to occur around the lips, eyes, or genitalia. In addition, some affected individuals have at least one blue-black mole called a blue nevus.

Some people with Carney complex develop a rare tumor called psammomatous melanotic schwannoma. This tumor occurs in specialized cells called Schwann cells, which wrap around and insulate nerves. This tumor is usually benign, but in some cases it can become cancerous (malignant).  https://medlineplus.gov/genetics/condition/carney-complex

Term Hierarchy

Professional guidelines

PubMed

Akkuş G, Korbonits M
Arch Med Res 2023 Dec;54(8):102920. Epub 2023 Nov 24 doi: 10.1016/j.arcmed.2023.102920. PMID: 38007383
Vamvoukaki R, Chrysoulaki M, Betsi G, Xekouki P
Medicina (Kaunas) 2023 Apr 21;59(4) doi: 10.3390/medicina59040812. PMID: 37109772Free PMC Article
Coopmans EC, Korbonits M
Clin Endocrinol (Oxf) 2022 Oct;97(4):424-435. Epub 2022 Mar 29 doi: 10.1111/cen.14706. PMID: 35349723

Recent clinical studies

Etiology

Ladd R, Davis M, Dyer JA
Clin Dermatol 2020 Jul-Aug;38(4):432-454. Epub 2020 Mar 30 doi: 10.1016/j.clindermatol.2020.03.007. PMID: 32972602
Guilmette J, Nosé V
Histopathology 2018 Jan;72(1):70-81. doi: 10.1111/his.13373. PMID: 29239041
Siordia JA
J Card Surg 2015 Jul;30(7):560-7. Epub 2015 May 21 doi: 10.1111/jocs.12575. PMID: 25996461
Lehmann AR, McGibbon D, Stefanini M
Orphanet J Rare Dis 2011 Nov 1;6:70. doi: 10.1186/1750-1172-6-70. PMID: 22044607Free PMC Article
Horvath A, Stratakis CA
Pigment Cell Melanoma Res 2009 Oct;22(5):580-7. Epub 2009 Jul 24 doi: 10.1111/j.1755-148X.2009.00613.x. PMID: 19650827Free PMC Article

Diagnosis

Akkuş G, Korbonits M
Arch Med Res 2023 Dec;54(8):102920. Epub 2023 Nov 24 doi: 10.1016/j.arcmed.2023.102920. PMID: 38007383
Vamvoukaki R, Chrysoulaki M, Betsi G, Xekouki P
Medicina (Kaunas) 2023 Apr 21;59(4) doi: 10.3390/medicina59040812. PMID: 37109772Free PMC Article
Lodish MB, Keil MF, Stratakis CA
Endocrinol Metab Clin North Am 2018 Jun;47(2):451-462. doi: 10.1016/j.ecl.2018.02.008. PMID: 29754644Free PMC Article
Alband N, Korbonits M
Handb Clin Neurol 2014;124:339-60. doi: 10.1016/B978-0-444-59602-4.00023-X. PMID: 25248598
Espiard S, Bertherat J
Front Horm Res 2013;41:50-62. Epub 2013 Mar 19 doi: 10.1159/000345669. PMID: 23652670

Therapy

Pitsava G, Zhu C, Sundaram R, Mills JL, Stratakis CA
Genet Med 2021 Jan;23(1):80-85. Epub 2020 Sep 7 doi: 10.1038/s41436-020-00956-3. PMID: 32893266Free PMC Article
Maillet M, Bourdeau I, Lacroix A
Curr Opin Endocrinol Diabetes Obes 2020 Jun;27(3):132-139. doi: 10.1097/MED.0000000000000538. PMID: 32209819
Stratakis CA
Ann Endocrinol (Paris) 2018 Jun;79(3):125-131. Epub 2018 Apr 9 doi: 10.1016/j.ando.2018.03.010. PMID: 29650225
Lonser RR, Mehta GU, Kindzelski BA, Ray-Chaudhury A, Vortmeyer AO, Dickerman R, Oldfield EH
Neurosurgery 2017 May 1;80(5):780-786. doi: 10.1227/NEU.0000000000001384. PMID: 27509071Free PMC Article
Gourgari E, Saloustros E, Stratakis CA
Curr Opin Pediatr 2012 Aug;24(4):518-22. doi: 10.1097/MOP.0b013e328355a279. PMID: 22732638Free PMC Article

Prognosis

Graham RP
Surg Pathol Clin 2018 Jun;11(2):377-387. Epub 2018 Mar 21 doi: 10.1016/j.path.2018.02.006. PMID: 29751881
Siordia JA
J Card Surg 2015 Jul;30(7):560-7. Epub 2015 May 21 doi: 10.1111/jocs.12575. PMID: 25996461
Espiard S, Bertherat J
Front Horm Res 2013;41:50-62. Epub 2013 Mar 19 doi: 10.1159/000345669. PMID: 23652670
Lehmann AR, McGibbon D, Stefanini M
Orphanet J Rare Dis 2011 Nov 1;6:70. doi: 10.1186/1750-1172-6-70. PMID: 22044607Free PMC Article
Bertagna X, Guignat L, Groussin L, Bertherat J
Best Pract Res Clin Endocrinol Metab 2009 Oct;23(5):607-23. doi: 10.1016/j.beem.2009.06.001. PMID: 19945026

Clinical prediction guides

Bonnet-Serrano F, Bertherat J
Endocr Relat Cancer 2018 Mar;25(3):R131-R152. Epub 2017 Dec 12 doi: 10.1530/ERC-17-0361. PMID: 29233839
Espiard S, Bertherat J
Front Horm Res 2013;41:50-62. Epub 2013 Mar 19 doi: 10.1159/000345669. PMID: 23652670
Vezzosi D, Vignaux O, Dupin N, Bertherat J
Ann Endocrinol (Paris) 2010 Dec;71(6):486-93. Epub 2010 Sep 17 doi: 10.1016/j.ando.2010.08.002. PMID: 20850710
Frohman LA, Eguchi K
Growth Horm IGF Res 2004 Jun;14 Suppl A:S90-6. doi: 10.1016/j.ghir.2004.03.021. PMID: 15135786
Sandrini F, Stratakis C
Mol Genet Metab 2003 Feb;78(2):83-92. doi: 10.1016/s1096-7192(03)00006-4. PMID: 12666684

Recent systematic reviews

Wang H, Mao M, Liu D, Duan L
Front Endocrinol (Lausanne) 2022;13:951133. Epub 2022 Sep 23 doi: 10.3389/fendo.2022.951133. PMID: 36213268Free PMC Article
Alvarado-Villacorta R, Torres Zavala NM, Marroquín Loayza L, Rodríguez-Reyes AA
Surv Ophthalmol 2022 May-Jun;67(3):729-740. Epub 2021 Aug 27 doi: 10.1016/j.survophthal.2021.08.007. PMID: 34461119
Georgiev GK, Todorov IV, Shamov TP, Krushovenski IV, Fakirova AD, Ilcheva BN, Georgiev IT, Georgiev ND, Prandjev VS, Eftimov TN
Folia Med (Plovdiv) 2021 Jun 30;63(3):448-456. doi: 10.3897/folmed.63.e55295. PMID: 34196157
Del Gobbo A, Peverelli E, Treppiedi D, Lania A, Mantovani G, Ferrero S
Exp Cell Res 2016 Aug 1;346(1):85-90. Epub 2016 Jun 16 doi: 10.1016/j.yexcr.2016.06.004. PMID: 27321957
Lau D, Rutledge C, Aghi MK
Neurosurg Focus 2015 Feb;38(2):E11. doi: 10.3171/2014.10.FOCUS14700. PMID: 25639313

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