Molecular genetics in childhood hypertension

Significant progress has been made in recent years in the elucidation of th e molecular genetic basis for several rare forms of hypertension that are o ften first diagnosed in childhood. This review summarizes these findings. G lucocorticoid remediable aldosteronism has been shown to be caused by unequ al crossing over between the genes for 11 beta-hydroxylase and aldosterone synthase so that corticotropin (ACTH) becomes the major controller of the l atter enzyme activity, meaning greatly elevated aldosterone synthesis and t hus sodium retention, volume expansion and high blood pressure. Mutations i n the 11 beta-hydroxylase gene are the cause of 11 beta-hydroxylase deficie ncy, another form of childhood hypertension. Apparent mineralocorticoid exc ess has been found to involve mutation of the gene encoding 11 beta-hydroxy steroid dehydrogenase type 2, which means instead of being destroyed in ald osterone target cells in the kidney, cortisol is able to bind to the minera locorticoid receptor, leading to greatly enhanced sodium reabsorption by th e kidney. Liddle's syndrome is another condition seen early in life and can involve mutations in the carboxyl terminal region of the beta- or gamma-su bunits of the amiloride-sensitive epithelial sodium channel gene. This prev ents binding of a protein that tags the channel for endocytosis and degrada tion so that channel activity is increased. Other forms of hypertension of early onset such as Gordon's syndrome, pheochromocytoma and brachydactyly a re also discussed. The review thus highlights the major advances that have occurred in understanding the molecular basis for various forms of hyperten sion seen in children. (C) 1999 Elsevier Science Ireland Ltd. All rights re served.