FaCD Online Syndrome Fact Sheet

Last updated: 27 May 2009

Name: Carney Complex

Synonym: Carney syndrome, NAME syndrome, LAMB syndrome, Familial Myxoma syndrome

Mode of Inheritance: AD

Genes

CNC2#, mapped to 2p15-p16
PRKAR1A, mapped to 17q22-q24

Tumor features

adrenocortical disease, primary pigmented nodular (PPNAD)
breast myxoma
cardiac myxoma
ductal adenoma of the breast
ear canal myxoma
gastrointestinal schwannoma
pituitary gland tumor
schwannoma (neurilemmoma), peripheral nerve
schwannoma of the bone
schwannoma, psammomatous melanotic
schwannomas of the (posterior) spinal nerve roots
skin myxoma
testicular Sertoli-Leydig cell tumor
thyroid cancer, follicular
uterine leiomyoma

Tumor features (possible)

cervical mesenchymal tumor, atypical
colorectal adenomas
pancreas, intraductal papillary mucinous tumor of the
paranasal sinuses, melanoma of the
peripheral nerve tumor
pheochromocytoma
teratoma, benign cystic (dermoid cyst) of the ovary
vestibular schwannoma

Non-tumor features

blue nevi
café au lait spots
lentiginosis (spotty pigmentation)
lips, pigmentation of
oral mucosa, pigmentation of

Non-tumor features (possible)

esophagus, Barrett

Comment

More than 200 patients have been reported, half of them familial cases. Patients present with spotty multiple small brown to black macules (lentiginosis) on the skin and mucosae (67 % of patients). Other pigmented lesions are cafe-au-lait spots, (epithelioid) blue nevi (19 % of patients) and less frequently psammomatous melanotic schwannoma (neurilemmoma) [1]. Primary pigmented nodular adrenocortical disease (PPNAD) leading to Cushing disease is also typical for the syndrome (found in 33 % of the patients).

A range of tumors can be found in Carney complex, including myxomas of heart (in 30-61 % of the patients), breasts (20%), skin (37%) (of the eyelids in 25 %) and external ear canal, testicular tumors (30%): testicular large cell calcifying Sertoli tumors (LCCST) and, less frequently, Leydig cell tumors, growth hormone producing pituitary adenomas (11 %) and schwannomas of upper g.i. tract, bone, sympatic chain and the skin (as mentioned above) (total % schwannomas found in Carney complex: 11). Thyroid gland involvement is common (11%), ranging from follicular hyperplasia to cancer. [2-4]. Nwokoro et al.[5] reported an affected 34-year-old woman from a Carney complex family, who in addition to features typical for this disorder also developed an atypical mesenchymal tumor of the cervix, neoplastic colonic polyps and a Barrett esophagus. Malignant melanoma of the maxillary sinus in a 6-year-old boy with Carney complex has recently been reported[14]. Pery et al[15] reported two brothers with Carney complex and diagnosed in their late 40s/early 50s with an intraductal papillary mucinous tumor.

There is evidence for genetic heterogeneity in Carney complex[4;6;7;7;8]. In some families, linkage analysis may help in identifying affected relatives[9]. Germline mutations in the PRKAR1A gene have been detected in approximately 45% of Carney complex cases and can also be found in isolated familial myxoma and familial or isolated cases of PPNAD[10;11,13].

Criteria[4;5;12]: 2 of the following should be present:

• a) Heart myxoma
• b) Breast myxoma (myxoid mammary fibroadenoma)
• c) Skin myxoma
• d) Primary pigmented nodular adrenocortical disease
• e) GH-secreting pituitary tumor
• f) Psammomatous melanotic schwannoma (PMS)
• g) Ductal adenoma of the breast
• h) Large-cell calcifying Sertoli cell tumor of the testes (LCCST)
• i) Spotty pigmentation if it is: multiple, present in a characteristic distribution (vermilion border of the lips, conjunctivae, external genitalia), not dependent on exposure to sunlight and has histology consistent with lentigo rather than ephelide (freckle).

References

[1] Carney JA, Stratakis CA. Epithelioid blue nevus and psammomatous melanotic schwannoma: The unusual pigmented skin tumors of the Carney complex. Semin Diagn Pathol 15[3], 216-224. 1998.
[2] Stratakis CA, Courcoutsakis NA, Abati A, Filie A, Doppman JL, Carney JA, Shawker T. Thyroid gland abnormalities in patients with the syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (Carney complex). J Clin Endocrinol Metab 82[7], 2037-2043. 1997.
[3] Scherer K, Muller T, Stolz W, Aebert H, Schunkert H. Carney complex: report of a case. Dtsch Med Wochenschr 123[33], 972-976. 1998.
[4] Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, Pras E, Chrousos GP. 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 97[3], 699-705. 1996.
[5] Nwokoro NA, Korytkowski MT, Rose S, Gorin MB, Stadler MP, Witchel SF, Mulvihill JJ. Spectrum of malignancy and premalignancy in Carney syndrome. Am J Med Genet 73[4], 369-377. 1997.
[6] Irvine AD, Armstrong DKB, Bingham EA, Hadden DR, Nevin NC, Hughes AE. Evidence for a second genetic locus in Carney complex. Br J Dermatol 139[4], 572-576. 1998.
[7] Milunsky J, Huang XL, Baldwin CT, Farah MG, Milunsky A. Evidence for genetic heterogeneity of the Carney complex (Familial atrial myxoma syndromes). Cancer Genet Cytogenet 106[2], 173-176. 1998.
[8] Stratakis CA, Kirschner LS, Taymans SE, Vaughan CJ, Hatcher CJ, Casey M, Carney JA, Basson CT. Genetic heterogeneity in Carney complex (OMIM 160980); contributions of loci at chromosomes 2 and 17 in its genetics. Am J Hum Genet 65[4]. 1999. Ref Type: Abstract
[9] Goldstein MM, Casey M, Carney JA, Basson CT. Molecular genetic diagnosis of the familial myxoma syndrome (Carney Complex). Am J Med Genet 1999; 86:62-65.
[10] Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, Cho Chung YS, Stratakis CA. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. NATURE GENETICS 2000; 26(1):89-92.
[11] Casey M, Vaughan CJ, He J, Hatcher CJ, Winter JM, Weremowicz S, Montgomery K, Kucherlapati R, Morton CC, Basson CT. Mutations in the protein kinase A R1 alpha regulatory subunit cause familial cardiac myxomas and Carney complex. JOURNAL OF CLINICAL INVESTIGATION 2000; 106(5):R31-R38.
[12] 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 80[2], 183-185. 1998.
[13] Boikos SA, Stratakis CA. Carney complex: the first 20 years. Current opinion in oncology 2007; 19(1):24-9.
[14] Ryan MW, Cunningham S, Xiao SY. Maxillary sinus melanoma as the presenting feature of Carney complex. International journal of pediatric otorhinolaryngology 2008; 72(3):405-8.
[15] Pery C Jr, Avallone S, Regenet N, Coron E, Le Borgne J.Intraductal papillary mucinous tumor of the pancreas in 2 twin brothers diagnosed as having the carney complex. Pancreas. 2009 Mar;38(2):237-9