Type I familial aldosteronism also called dexamethasone suppressible aldosteronism is a rare disorder inherited as an autosomal dominant trait. It is due to the ectopic expression of the aldosterone synthase in the fascicular zone of the adrenal gland. It is marked with early severe hypertension (often occurring before the age of 20), biological signs of primary aldosteronism of variable intensity, and an abnormal elevated level of 18-oxo- and 18-hydroxycortisol. The molecular defect is a recombination on the long arm of chromosome 8 leading a duplication-fusion between the 5' end of the gene coding for the 11 beta-hydroxylase (CYP11B1) and the 3' end of the gene coding for the aldosterone synthase (CYP11B2), two very similar (93%) and very closely located genes. All the modifications are located before the exon 5 of CYP11B2 which encodes amino acids allowing the aldosterone synthase function. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2. This leads an excessive mineralocorticoids synthesis in the adrenal glands, governed by the hypothalamohypophyseal axis. Diagnosis and familial screening consist in providing evidence of the hybrid gene by Southern blot and/or PCR. Urinary tests show an important elevation of 18-oxo- and 18-hydroxycortisol. Once the diagnosis is ascertained, a specific treatment to slow the production of aldosterone is given; it combines small doses of dexamethasone and an anti-aldosterone.
Last update: September 2000