儿童垂体柄阻断综合征的临床及基因研究

Childhood pituitary stalk interruption syndrome: a clinical-genetic study

目的探讨儿童垂体柄阻断综合征的临床表现及基因突变类型。方法选取2016年1月至2018年3月首都儿科研究所附属儿童医院内分泌科收治的垂体柄阻断综合征患儿16例,回顾性分析患儿的临床表现,并采用全外显子测序技术进行基因学检测,根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)指南对其致病性进行分析。结果共纳入16例垂体柄阻断综合征患儿,诊断年龄为1.7～16.2岁,男11例,女5例;4例有臀位产病史,11例以"身高增长缓慢"就诊,4例以"反复无热抽搐"为主要表现。16例患儿均为生长激素缺乏,其中15例有中枢性甲状腺功能减退,11例继发性肾上腺皮质功能不全。2例发现致病性突变,其中1例为4.9岁男孩,为ROBO1基因c.1690C>T(p.Pro564Ser)杂合突变,1例为12.3岁女孩,为HS6ST1基因c.608C>T(p.Thr203Met)杂合突变,均符合ACMG致病性突变,生物学预测有害。结论垂体柄阻断综合征临床上以患儿身高增长缓慢最为常见,多表现为联合垂体功能减退,全外显子测序有利于发现致病性突变。

Objective To analyze the characteristics of childhood pituitary stalk interruption syndrome(PSIS) and genetic etiology. Method Patients initially diagnosed as PSIS during January 2016 and March 2018 in the Department of Endocrinology of Capital Institute of Pediatrics Affiliated Children Hospital were retrospectively studied. Whole-exome capture and NGS were performed in all the patients mentioned above, standard interpretation according to ACMG guideline. Result 16 PSIS cases were recruited, the diagnostic age was 1.7- 16.2 years, 11 patients were male, 5 patients were female, 4 patients had breech presentation. 11 patients presented growth retardation, 4 patients presented seizure afebrile. All of the 16 patients were identified with growth hormone deficiency, 15 patients were identified with pituitary hypothyroidism, 11 patients were identified with secondary adrenal insufficiency. A ROBO1 mutation (c.1690C >T, p.Pro564Ser) was found in a 4.9 year male patient, a HS6ST1 mutation (c.608C >T, p.Thr203Met) was found in a 12.3 year female patient. Both of the two mutations were predicted to be deleterious substitutions for protein function. Conclusion Main complaints of patients with PSIS are decreasing growth velocity, such patients usually manifest combined pituitary hormone deficiency, whole-exome sequencing is applied to find causative mutations.