CHARGE综合征伴甲状腺功能减退症：一例病例报告

文献信息

中文摘要

背景： CHARGE综合征（CS）是一种由染色质域解旋酶DNA结合蛋白7（CHD7）基因突变引起的罕见遗传性疾病。CS的特征是一系列疾病，包括缺损、心脏畸形、后鼻孔闭锁、生长和发育迟缓、生殖器发育不全以及耳部异常和/或耳聋。此外，一些CS患者可能患有某种类型的内分泌疾病，这会影响他们的发育。
病例描述： 我们报告一例6个月大女婴，诊断为CS和先天性甲状腺功能减退症（CH），表现为多种特征，包括歪嘴笑、贫血、右耳耳廓畸形和听觉异常、房间隔缺损和动脉导管未闭以及严重生长迟缓。全外显子组测序（WES）和线粒体基因组测序显示CHD7基因杂合突变[c.2377-1G>A（NM_017780.4）]和双氧化酶成熟因子2（DUOXA2）基因杂合突变[c.413dup(p.Tyr138Ter)]。患者接受了左甲状腺素口服补充、康复训练以及高能量密度配方和辅食喂养。还使用了呋塞米、氢氯噻嗪和地高辛片治疗肺动脉高压。当患者14个月大时，她表现出生长改善，语言发育比之前更好，但与健康同龄人相比仍持续延迟。
结论： 本病例强调了早期遗传诊断和干预不仅对CS而且对其他内分泌疾病的重要性。此外，作为一种多系统疾病，CS需要多学科医生的努力才能成功治疗。

英文摘要

BACKGROUND: CHARGE syndrome (CS) is a rare genetic disorder caused by mutations in the chromodomain helicase DNA binding protein 7 (CHD7)gene. CS is characterized by a spectrum of disorders, including coloboma, heart malformations, atresia choanae, retarded growth and development, genital hypoplasia, and ear abnormalities and/or deafness. Additionally, some patients with CS may have some type of endocrine disorder, which affects their development.
CASE DESCRIPTION: We report the case of a 6-month-old female infant diagnosed with CS and congenital hypothyroidism (CH) who presented with various features, including a crooked smile, anemia, auricular deformity and auditory abnormalities of the right ear, atrial septal defect and patent ductus arteriosus, and severe growth retardation. Whole-exome sequencing (WES) and mitochondrial genome sequencing showed a heterozygous mutation of the CHD7 gene [c.2377-1G>A (NM_017780.4)] and a heterozygousdual oxidase maturation factor 2 (DUOXA2) gene mutation [c.413dup(p.Tyr138Ter)]. The patient was provided oral supplementation of levothyroxine, rehabilitation training, and feeding with a high-energy density formula and complementary foods. Furosemide, hydrochlorothiazide, and digoxin tablets were also administered for pulmonary hypertension. When the patient was 14 months old, she showed improved growth, and language development was better than before, but these continued to be delayed compared to healthy peers.
CONCLUSIONS: This case highlights the importance of an early genetic diagnosis and intervention not only for CS but also for other endocrine disorders. Additionally, as a multi-system disease, CS requires the efforts of doctors from multiple disciplines for its successful treatment.