Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome

Abstract

Latent hypoparathyroidism (LHP), the inability to increase midmolecular parathyroid hormone levels appropriately during a hypocalcemic challenge, was reported previously in an asymptomatic woman with tetralogy of Fallot. This women's fourth child died with DiGeorge anomaly. Seven years later, we restudied the index patient with LHP and evaluated three generations of her family for parathyroid dysfunction, cardiac abnormalities, and del 22(q11). Deletions were found in six relatives, three with conotruncal cardiac defects and three with a structurally normal heart. We found significant transgenerational noncardiac phenotypic variability, including learning difficulties, dysmorphic facial appearance, and psychiatric illness. A spectrum of parathyroid gland dysfunction associated with the del 22(q11) was seen, ranging from hypocalcemic hypoparathyroidism to normocalcemia with abnormally low basal intact parathyroid hormone (iPTH) levels. In addition, LHP found in the index patient 7 years ago had evolved to frank hypocalcemic hypoparathyroidism. In this family, which is the largest family with 22q11 deletions studied to date, parathyroid gland dysfunction evolved over time. We suggest that the calcium parathyroid hormone axis of unrelated patients with del 22(q11) be followed closely for the development of hypocalcemic hypoparathyroidism.