Familial isolated hypoparathyroidism

Familial isolated hypoparathyroidism is the term generally used to describe inherited disorders that manifest almost exclusively as a deficiency of parathyroid hormone. More than a handful of cases, recessive and dominant, arise from mutations of the parathyroid hormone gene (PTH), while there are now more than 20 cases attributable to the developmental gene, glial cells missing 2 (GCM2). Gain-of-function mutations of the calcium-sensing receptor gene (CASR) are responsible for the most common condition, now termed ADH1 and characterized by concomitant hypercalciuria. A few families appear to have hypoparathyroidism due to a mutation of the gene encoding Gα11 protein (GNA11). Finally, X-linked inheritance of FIH is also known. In most cases, a search for a molecular lesion should be considered an integral part of the patient work-up. Still remaining, though, are a good number of families for whom no mutation has been identified. They represent an important future challenge for investigators of this condition.