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.

Whole genome sequencing resolves 10 years diagnostic odyssey in familiar myxoma

“…It is also characteristic for Noonan syndrome with multiple lentigines (NSML) or Peutz-Jeghers-syndrome, however its presence on the lacrimal caruncle, the border of the lips, and eyelid margins is considered the hallmark of CNC. Specific localisations of cutaneous myxomas are the external ear canal, upper eyelids, and areola mammae; however, multiple large myxomas are uncommon 25 . They may be mistaken for neurofibromas, therefore histological examination is always recommended.…”

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].…”