Dermatological and endocrine elements in Carney complex (Review)

Abstract

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the CNC1 gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (PRKAR1A), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumors with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.

Xeroderma pigmentosum: an updated review

“…The differential diagnosis includes Cockayne syndrome, XP/Cockayne syndrome complex, trichothiodystrophy, XP/trichothiodystrophy complex, Cockayne syndrome/ trichothiodystrophy complex, cerebro-oculo-facio-skeletal (COFS) syndrome, UV-sensitive syndrome, Bloom syndrome (also known as Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema), Rothmund-Thomson syndrome, Hartnup disease, Carney complex, De Sanctis-Cacchione syndrome, erythropoietic protoporphyria, cutaneous lupus erythematosus and LEOPARD syndrome (also known as Noonan syndrome with multiple lentigines). [83][84][85][86][87][88][89][90][91][92][93][94][95][96] The distinctive features of many of these conditions help to differentiate them from XP.…”

Carney complex- why thorough medical history taking is so important - report of three cases and review of the literature

“…after puberty [53,54] typically, multiple Ovarian lesions common [55,56] ovarian cysts, serous cystadenomas and cystic teratomas after puberty rarely progress to ovarian carcinoma [55,56] Testicular tumors up to 75% large cell-calcifying Sertoli cell tumors (LCCSCT) [57,58] childhood increased risk of reduced fertility [59,60] and malignancy in adults [61,62], malignancy rate 17% [63] physicians should be aware of these very rare testicular tumors representing <1% of all testicular neoplasms [57,58] and their possible connection to CNC Bone lesions 1% osteochondromyxoma [7], 31.6% vertebral nodular lesions [64] osteochondromyxoma: usually early childhood [7]; vertebral lesions interpreted as osteochondromyxomas 30-40 years [64] osteochondromyxomas have the potential to be locally invasive and to recur [65] typically associated with CNC [66] Other tumors pancreatic neoplasias [67] as well as hepatic [68], colonic [69] or gastric tumors [70] CNC [15]. Other disease-related genes include activating PRKACA variants [17].…”