Carney complex and the familial lentiginosis syndromes: link to inherited neoplasias and developmental disorders, and genetic loci

Abstract

Abstract. Chrousos GP, Stratakis CA (National Institutes of Health, Bethesda, MD, USA). Carney complex and the familial lentiginosis syndromes: link to inherited neoplasias and developmental disorders, and genetic loci (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 573-9.

Carney Complex: Pathology and Molecular Genetics

“…Endocrine gland involvement includes GH-secreting pituitary adenomas, thyroid gland disease, corticotropin (ACTH)-independent Cushing syndrome secondary to PPNAD and testicular tumors, in particular LCCSCT [5,6,7,8,9]. PPNAD causes the greatest degree of endocrine-associated morbidity and seems to be the most common endocrine lesion, occurring in about one quarter of the patients.…”

Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes

“…Despite the apparent differences between the main types of familial lentiginoses, they share many clinical manifestations. This finding is further supported by a number of patients with lentigines who have features that could fit under any of the mentioned syndromes: One example is a kindred with lentiginosis and vascular malformations of the gastrointestinal system, and another is patients with lentigines, myxomas, and intestinal polyps (10,42,78).…”

“…Multiple intramuscular myxomas occasionally occur in MAS, a disorder that manifests CALS and may feature acromegaly and Cushing syndrome, the latter arising from adrenal cortical hyperplasia rather than PPNAD, however (2). Finally, there are similarities between the MEN syndromes and Carney complex: Lesions are often bilateral and multifocal; somatotropinomas, lipomas and other benign skin lesions are common to both MEN 1 and the complex; and adrenal pathology is present in both conditions (10,19,42). In addition, the distribution of the facial lesions in MEN 2B and the Carney complex has a curious and remarkable anatomical symmetry: the eyelids, lips, tongue, and ears are affected in both syndromes.…”

“…It is evident that the syndrome shares components (lentiginosis, Cushing syndrome, acromegaly, thyroid and gonadal tumors) (10,19), a transmission pattern (autosomal dominant inheritance with possible parent of origin effects) (41), and a pattern of organ involvement (bilateral and multifocal involvement in the case of paired organs) with other syndromes (42). Among these, two that feature spotty skin pigmentation, the Peutz-Jeghers and LEOPARD syndromes, have components in common with Carney complex.…”

“…The lentiginoses constitute a group of diseases that share melanocytic hyperplasia as their feature and affect a variety of organs of the cardiovascular, endocrine, and gastrointestinal systems (42). They represent overlap syndromes with the familial neoplasias and certain, diverse developmental defects (Figure 7).…”