ACTH resistance syndromes

ACTH resistance syndromes consist of a group of rare disorders with three V arious molecular etiologies. However, ail these diseases share the feature of severe glucocorticoid adrenal insufficiency. The simplest disorder is th e isolated familial glucocorticoid deficiency (FGD) which could be divided in two different types. in FGD type 1,ACTH receptor mutations have been des cribed and are responsible for the loss of function of the receptor, leadin g to the ACTH unresponsiveness. Patients with FGD type 2 show the same phen otype as in the previous syndrome but no mutation of the ACTH receptor has been reported in these cases, it has been proposed that morbidity of one or several other gene(s) could be responsible for this syndrome although ther e is no information about their chromosomal localization. The third molecul ar form of the disease corresponds to the Triple A syndrome for the triad o f association " ACTH resistance, Achalasia, Alacrima ", thus reflecting a l arge spectrum of additional symptoms. It has recently been reported that th e morbid gene in this last syndrome maps to chromosome 12q13. The aim of th is review is to examine the clinical aspect as well as the current knowledg e of the molecular and genetic aspects of the different forms of the diseas e.