Guan Bin, Agarwal Sunita K, Welch James M, Jha Smita, Weinstein Lee S, Simonds William F
Ophthalmic Genomics Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
JCEM Case Rep. 2024 Jul 24;2(8):luae115. doi: 10.1210/jcemcr/luae115. eCollection 2024 Aug.
A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease.
一名51岁女性，有原发性甲状旁腺功能亢进症（PHPT）病史，曾行甲状旁腺切除术，患有骨质疏松症和学习障碍，因跌倒后发现高钙血症前来就诊。家族史中无PHPT、垂体、肠胰神经内分泌或颌骨肿瘤。观察到患者有面容畸形、多处皮肤黑素细胞痣、咖啡斑、手指细长和脊柱侧弯。实验室检查显示甲状旁腺激素（PTH）水平升高、高钙血症和低磷血症，均与PHPT相符。术前影像学检查发现右下方有一个疑似甲状旁腺病变。患者接受了右下方甲状旁腺切除术，术后PTH、钙和磷水平恢复正常。基因检测显示，在一个编码锌指转录因子的基因中存在一个可能致病的新生杂合种系错义变体p.R764W，该转录因子先前在一部分散发性甲状旁腺肿瘤中存在体细胞错义变体。在患有X连锁智力残疾综合征且先天性异常和PHPT风险增加的患者中，已报道了该基因的种系变体。进一步的研究可能会确定，即使没有甲状旁腺疾病家族史，对该基因进行基因检测是否对患有PHPT和发育异常的患者有潜在益处。
