FaCD Online Syndrome Fact Sheet

Last updated: 07 Feb 2008

Name: Primary Pigmented Nodular Adrenocortical Disease, Familial

Synonym: iPPNAD, PPNAD1, incl. familial micronodular adrenocortical hyperplasia, PPNAD2

Mode of Inheritance: AD

Genes

PDE11A, mapped to 2q31.2
PRKAR1A, mapped to 17q22-q24

Tumor features

adrenocortical disease, primary pigmented nodular (PPNAD)
micronodular adrenal hyperplasia

Non-tumor features

adrenal hyperplasia

Comment

Primary Pigmented Nodular Adrenocortical Disease (PPNAD)is one of the causes of bilateral adrenal Cushing's disease. PPNAD is a frequent feature of Carney complex, a disoder associated with germline PRKAR1A mutations. Approximately 80-90% of patients with PPNAD have Carney complex. The hot spot PRKAR1A mutation c.709[-7-2]del6 predisposes mostly to isolated PPNAD. However, PRKAR1A mutations have not been abserved i patients with PPNAD who develope Cushing's disease before the age of 5 years.[1. Inactivating mutations of the PDE11A4 gene have been identified in familial micronodular adrenocortical hyperplasia patients without PRKAR1A mutations. Some of their tumors resembled PPNAD[2]

References

[1] Cazabat L, Ragazzon B, Groussin L, Bertherat J. PRKAR1A mutations in primary pigmented nodular adrenocortical disease. Pituitary 2006; 9(3):211-9.
[2] Horvath A, Boikos S, Giatzakis C, Robinson-White A, Groussin L, Griffin KJ, Stein E, Levine E, Delimpasi G, Hsiao HP, Keil M, Heyerdahl S, Matyakhina L, Libè R, Fratticci A, Kirschner LS, Cramer K, Gaillard RC, Bertagna X, Carney JA, Bertherat J, Bossis I, Stratakis CA. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nature genetics 2006; 38(7):794-800.