Department of Pediatrics, Jeonbuk National University Hospital, Jeonju, Korea.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Endocr J. 2022 Oct 28;69(10):1211-1216. doi: 10.1507/endocrj.EJ22-0084. Epub 2022 Jul 8.
Multiple endocrine neoplasia type 2A (MEN2A) is caused by germline pathogenic variants in the RET proto-oncogene and is characterized by medullary thyroid cancer (MTC), pheochromocytoma, and hyperparathyroidism. Autoimmune polyendocrine syndromes (APS) are defined as multiple endocrine gland insufficiency associated with loss of immune tolerance. APS type 2 (APS-2) consists of at least two of the following diseases: type 1 diabetes mellitus (T1DM), autoimmune thyroid disease, and Addison's disease. We describe the clinical, molecular, and biochemical findings of MEN2A, APS-2, and Kabuki syndrome (KS) in a 16-year-old male. Whole exome sequencing was performed to identify the genetic cause of the pheochromocytoma and syndromic features including facial dysmorphism, developmental delay, and epilepsy. RET pathogenic variant and KMT2D pathogenic variant were identified, and he was diagnosed with MEN2A and KS. This is the first case of association between MEN2 and APS in adolescence and the second proven case in humans. In addition, this is the first report of MEN2 and APS in KS.
2A 型多发性内分泌肿瘤(MEN2A)是由原癌基因 RET 种系致病性变异引起的,其特征是甲状腺髓样癌(MTC)、嗜铬细胞瘤和甲状旁腺功能亢进症。自身免疫性多内分泌腺病综合征(APS)的定义是与免疫耐受丧失相关的多种内分泌腺功能减退。APS 型 2(APS-2)至少包括以下两种疾病:1 型糖尿病(T1DM)、自身免疫性甲状腺疾病和艾迪生病。我们描述了一名 16 岁男性的 MEN2A、APS-2 和歌舞伎综合征(KS)的临床、分子和生化发现。进行了全外显子组测序,以确定嗜铬细胞瘤和综合征特征的遗传原因,包括面部畸形、发育迟缓、癫痫。鉴定出 RET 致病性变异和 KMT2D 致病性变异,诊断为 MEN2A 和 KS。这是青春期 MEN2 和 APS 之间关联的首例病例,也是人类中第二例证实的病例。此外,这是 MEN2 和 KS 中 APS 的首次报道。