Carney complex

Definition: Carney complex (CNC) is a rare heritable disorder including cutaneous lentigines, myxomas of skin, subcutaneous tissueand heart and endocrine neoplasms. Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS).

Its features overlap those of other multiple endocrine neoplasias and hamartomatoses, Peutz-Jeghers syndrome (PJS) in particular.

(The Carney syndrome terminology is avoided because it can be confused with the Carney triad.)

Synopsis

 cutaneous lentigines
 blue nevi (epithelioid blue nevus) (10847545, 9711672)
 psammomatous melanotic schwannoma (9711672, 8434979)

• intraosseous melanotic schwannoma (16930334)

 myxomas

• skin (21880053)
• subcutaneous tissue
• breast
• heart / cardiac myxoma

 superficial angiomyxoma (12532046, 12532046)

 adrenal anomalies

• primary pigmented nodular adrenocortical disease (PPNAD) with familial Cushing’s syndrome (12424709) (27875378)
• adrenal cortex adenoma (27875378)
• myelolipoma (27875378)

 endocrine tumors

• adrenal cortex adenoma
• pituitary adenoma
• testis
• thyroid
• PRKAR1A-associated virilizing ovarian stromal tumor (21934476)

 schwannomas
 osteochondromyxoma of bone (11176065)
  ovarian cysts
 ovarian carcinomas

• endometrioid adenocarcinoma
• mucinous adenocarcinoma

  testicular tumors

• large-cell calcifying Sertoli cell tumor (11095480)

 pancreatic ductal and acinar cell tumors (21900385)

Etiology

 Locus CNC1 (MIM.160980) at 17q22-24: mutations in the PRKAR1A gene (MIM.188830) coding for the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (12424709)

 Locus CNC2 (MIM.605244) at 2p16 (12676898)

Open references

 Cushing Syndrome in Carney Complex: Clinical, Pathologic, and Molecular Genetic Findings in the 17 Affected Mayo Clinic Patients. Lowe KM, Young WF Jr, Lyssikatos C, Stratakis CA, Carney JA. Am J Surg Pathol. 2017 Feb;41(2):171-181. doi : 10.1097/PAS.0000000000000748 PMID: 27875378

 Ovarian lesions in Carney complex: clinical genetics and possible predisposition to malignancy. Stratakis CA, Papageorgiou T, Premkumar A, Pack S, Kirschner LS, Taymans SE, Zhuang Z, Oelkers WH, Carney JA. J Clin Endocrinol Metab. 2000 Nov;85(11):4359-66. PMID: 11095480 [Free]

References

 Bossis I, Voutetakis A, Bei T, Sandrini F, Griffin KJ, Stratakis CA. Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer. 2004 Jun;11(2):265-80. PMID: 15163302

 Bossis I, Stratakis CA. PRKAR1A: normal and abnormal functions. Endocrinology. 2004 Dec;145(12):5452-8. PMID: 15331577

 Stratakis CA, Matyakhina L, Courkoutsakis N, Patronas N, Voutetakis A, Stergiopoulos S, Bossis I, Carney JA. Pathology and molecular genetics of the pituitary gland in patients with the ’complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas’ (Carney complex). Front Horm Res. 2004;32:253-64. PMID: 15281351

 Bossis I, Voutetakis A, Bei T, Sandrini F, Griffin KJ, Stratakis CA. Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer. 2004 Jun;11(2):265-80. PMID: 15163302