Cuneo B F, Driscoll D A, Gidding S S, Langman C B
Department of Pediatrics, Rush University Medical School, Chicago, Illinois, USA.
Am J Med Genet. 1997 Mar 3;69(1):50-5.
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.
隐匿性甲状旁腺功能减退症（LHP），即低钙血症激发试验期间无法适当增加中分子甲状旁腺激素水平，此前在一名患有法洛四联症的无症状女性中被报道。该女性的第四个孩子死于DiGeorge异常。七年后，我们重新研究了这位患有LHP的索引患者，并评估了她家族三代人是否存在甲状旁腺功能障碍、心脏异常和22号染色体长臂1区1带缺失（del 22(q11)）。在六名亲属中发现了缺失，其中三名患有圆锥动脉干心脏缺陷，三名心脏结构正常。我们发现了显著的跨代非心脏表型变异，包括学习困难、面部畸形和精神疾病。观察到一系列与del 22(q11)相关的甲状旁腺功能障碍，从低钙血症性甲状旁腺功能减退到基础完整甲状旁腺激素（iPTH）水平异常低的血钙正常情况。此外，7年前在索引患者中发现的LHP已发展为明显的低钙血症性甲状旁腺功能减退症。在这个家族中，是迄今为止研究的最大的一个有22q11缺失的家族，甲状旁腺功能障碍随时间演变。我们建议密切关注无关的del 22(q11)患者的钙-甲状旁腺激素轴，以观察低钙血症性甲状旁腺功能减退症的发展情况。
