A novel PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease and the Carney complex

Endocr Pract. 2010 Mar-Apr;16(2):198-204. doi: 10.4158/EP09245.OR.

Abstract

Objective: To delineate the genetic and phenotypic features of Carney complex in a family with multiple cases of primary pigmented nodular adrenocortical disease (PPNAD).

Methods: Detailed clinical, laboratory, genetic, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.

Results: A 17-year-old girl presented with symptoms and physical findings suggestive of hypercortisolemia, in addition to facial lentigines. She was found to have adrenocorticotropic hormone (ACTH)-independent Cushing syndrome. The adrenal glands appeared normal on computed tomographic scanning. Bilateral surgical adrenalectomy revealed PPNAD. Evaluation of her 14-year-old sister revealed ACTH-independent Cushing syndrome as well as facial lentigines, and adrenalectomy revealed PPNAD as well. Genetic testing of the 2 sisters and their mother (who also had multiple facial lentigines but did not have Cushing syndrome) revealed a novel mutation in the PRKAR1A gene.

Conclusion: We describe a novel mutation in the PRKAR1A gene in a family with Carney complex and multiple members with PPNAD. PPNAD should be suspected in cases of ACTH-independent Cushing syndrome, and screening for Carney complex and its complications is recommended in all cases of PPNAD, including first-degree relatives.

MeSH terms

  • Adolescent
  • Adrenal Cortex Diseases / genetics*
  • Carney Complex
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Mutation
  • Pedigree
  • Pigmentation Disorders / genetics*

Substances

  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • PRKAR1A protein, human