These can lead to GH secreting pituitary adenomas as an isolated occurrence (e.g. as aggressive sporadic adenomas or in familial isolated pituitary adenomas (FIPA)) or as part of syndromic conditions such as MEN1 or Carney complex.
More rarely, germline mutations predisposing to pituitary adenomas -as part of a syndrome (eg, MEN1 or Carney complex), or isolated to the pituitary (AIP or GPR101) can be identified.
We provide here a review of the clinical features and human molecular genetics of multiple endocrine neoplasia (MEN) type 1 and 4 (MEN1 and MEN4, respectively) and Carney complex (CNC).
Familial pituitary adenomas occur as part of a syndrome affecting other organs, such as in MEN1 or Carney complex, or occur with pituitary adenomas only as in familial isolated pituitary adenoma (FIPA).
To date, the number of molecular genetic factors unequivocally linked to pituitary tumours can be counted on the fingers of one hand: (1) GNAS1 activation in acromegaly; (2) the MENIN and p27Kip1 (CDKN1B) mutations associated with multiple endocrine neoplasia type 1; (3) mutations of PRKA1RA with loss of 17q22-24 in Carney complex, and (4) aryl hydrocarbon receptor interacting protein gene mutations in 15% of familial isolated pituitary adenomas and 50% of familial isolated acromegaly.
Familial pituitary adenomas occurr in the classical syndromes of MEN1 and Carney Complex as well as in Familial Isolated Pituitary Adenomas (FIPA), an autosomal dominant disease with incomplete penetrance.
Familial pituitary adenomas can occur in MEN1 and Carney complex, as well as in the recently characterized familial isolated pituitary adenoma (FIPA) syndrome.
Since the late 1990s we have described non-MEN1/CNC familial pituitary tumours that include all tumour phenotypes, a condition named familial isolated pituitary adenomas (FIPA).
Since the late 1990 s, we have described non-MEN1/CNC familial pituitary tumours that include all tumour phenotypes as a condition termed Familial Isolated Pituitary Adenomas (FIPAs).
First described in the mid 80's, Carney Complex (CNC) is a rare, dominantly heritable disorder with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1).
Carney complex (CNC) is a familial multiple neoplasia and lentiginosis syndrome with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1).
This review presents the newest information on the clinical and molecular genetics of the MENs (MEN 1, MEN 2, and Carney complex), including recommendations for genetic screening, and discusses briefly the related syndromes PJS, CD and VHLD.
The data (1) underline the need for early investigation for acromegaly in patients with CNC; (2) provide a molecular hypothesis for its clinical progression; and (3) suggest a model for MAS- and, perhaps, MEN 1-related GH-producing tumor formation.