6例Noonan综合征临床特点及治疗效果分析
发布时间：2018-12-20 13:10
【摘要】：Noonan综合征(Noonan syndrome,NS)是一种常染色体显性遗传性疾病,以身材矮小、特殊面容、先天性心脏病为主要表现。以往研究表明,重组人生长激素(Recombinant human growth hormone,rh GH)可显著改善NS患者的终身高。但是目前尚无中国关于NS患者的临床特点以及rh GH治疗反应的报道。本研究总结并分析了6例NS患者临床特征及rh GH治疗效果。针对2009年5月-2015年8月在北京协和医院内分泌科门诊就诊的6例疑似NS患者,进行一系列体格检查、实验室检查及基因筛查。并且以0.10-0.15IU/kg*d剂量应用rh GH,随后进行定期随访。同时与年龄/性别相匹配的应用rh GH的10例特纳综合征(Turner Sydrome,TS)和10例完全性生长激素缺乏症(Growth Hormone Deficiency)患者进行比较,分析治疗效果的差异。6例患者均存在NS的典型面容并可诊断为矮小症,5例并合并先天性心脏病,4例存在骨骼系统发育异常及不同程度的骨龄落后。6例患者通过基因检测均可明确诊断为NS,其中4例为PTPN11突变,1例KRAS突变,1例SOS1突变。5例经rh GH治疗后,年生长速度分别为:0个月(3.92±1.23)cm/y;3个月(8.36±2.57)cm/y;6个月(8.30±1.97)cm/y;9个月(9.33±4.46)cm/y;12个月(8.80±1.20)cm/y。除第9个月外,用药后3、6、12个月的生长速度较用药前显著增加(P0.01)。在1年随访期内,除1例患者进入3-10th之间外,余4例患者身高仍低于3th。与NS年龄匹配的10例TS患者在用药前及用药后第3、6个月的生长速度均高于NS患者,NS在用药前及用药后第9、12个月的生长速度均高于TS患者,但以上差异均无统计学意义(P0.05)。10例TS患者中,用药前有1例身高位于3~10th之间,余9例均3th,经1年rh GH治疗后,3例患者身高位于3~10th,余7例均3th;与NS年龄/性别相匹配的10例GHD患者在用药后第3、6个月的生长速度显著高于NS,差异有统计学意义(P0.05);GHD在用药前及用药后第9个月的生长速度均高于NS,而NS在用药后第12个月生长速度高于GHD,但以上差异均无统计学意义(P0.05)。10例GHD患者中,用药前有1例身高位于10~25th,1例位于3~10th,余8例均3th,经1年rh GH治疗后,3例患者身高从位于3th至3~10th,余7例百分位数保持不变。不良事件方面:6例NS、10例TS及10例GHD患者中,分别有2例、4例及2例在随访期出现了亚临床甲状腺功能减低,并及时应用雷替斯25ug/d纠正甲状腺功能。在随访期未发现rh GH相关的不良反应,如注射部位疼痛、皮疹、关节疼痛及血糖升高等。本研究中6例NS患者均存在不同程度的异常体征。NS、TS和GHD患者在应用rh GH后,年生长速度均较前明显增加且未出现严重不良反应。比较三者rh GH疗效可得出如下结论:NS与TS患者在rh GH方面疗效相似,随访各点均无显著性差异;但与年龄/性别相匹配的GHD患者相比,GHD患者在应用rh GH后疗效更显著。
[Abstract]:Noonan syndrome (Noonan syndrome,NS) is an autosomal dominant hereditary disease characterized by short stature, special face and congenital heart disease. Previous studies have shown that recombinant human growth hormone (Recombinant human growth hormone,rh GH) can significantly improve lifetime height in NS patients. However, there are no reports on the clinical characteristics of NS patients and the response to rh GH therapy in China. This study summarized and analyzed the clinical features of 6 patients with NS and the therapeutic effect of rh GH. From May 2009 to August 2015, a series of physical examination, laboratory examination and gene screening were performed on 6 suspected NS patients in the Department of Endocrinology, Peking Union Hospital. Rh GH, was given at 0.10-0.15IU/kg*d dose and followed by regular follow-up. At the same time, 10 patients with Turner's syndrome (Turner Sydrome,TS) and 10 patients with complete growth hormone deficiency (Growth Hormone Deficiency) were compared with age / gender matched patients with rh GH. Six patients had typical facial appearance of NS and could be diagnosed as dwarfism, and 5 patients with congenital heart disease, 5 patients with congenital heart disease. There were 4 cases of abnormal development of bone system and different degrees of bone age backwardness. 6 patients were diagnosed as NS, by gene test, including 4 cases of PTPN11 mutation, 1 case of KRAS mutation, 1 case of SOS1 mutation and 5 cases after rh GH treatment. The annual growth rate was 0 months (3.92 卤1.23) cm/y;, respectively. 3 months (8.36 卤2.57) cm/y; 6 months (8.30 卤1.97) cm/y; 9 months (9.33 卤4.46) cm/y; 12 months (8.80 卤1.20) cm/y. Except for the 9th month, the growth rate was significantly increased at 6 and 12 months after treatment (P0.01). During the 1 year follow-up period, except for one patient entering 3-10th, the other 4 patients were still below 3thth in height. The growth rate of 10 TS patients matched with the age of NS was higher than that of NS patients before treatment and at the 3rd and 6th month after treatment. The growth rate of NS was higher than that of TS patients before treatment and at the 9th and 12th month after treatment. But there was no significant difference (P0.05). Among the 10 patients with TS, 1 case was between 3~10th and 9 cases were 3th.After one year of rh GH treatment, 3 cases were at 3thth, and 7 cases were 3thth. The growth rate of 10 GHD patients matched with the age / sex of NS was significantly higher than that of NS, at the 3rd and 6th month after treatment (P0.05). The growth rate of GHD was higher than that of NS, before and 9 months after treatment, but the growth rate of NS was higher than that of GHD, at 12 months after treatment (P0.05). Before treatment, 1 case was located at 1010 th and 8 cases were 3 ths.After one year of rh GH treatment, 3 cases were located in 3th to 3thth, and the remaining 7 cases remained unchanged in percentile. Adverse events: in 6 cases of TS and 10 cases of GHD, 2 cases, 4 cases and 2 cases of GHD showed subclinical hypothyroidism during follow-up period, and immediately corrected thyroid function with 25ug/d. There were no adverse reactions associated with rh GH during follow-up, such as injection site pain, rash, joint pain and elevated blood glucose. In this study, 6 patients with NS had different degrees of abnormal signs. The annual growth rate of both NS,TS and GHD patients was significantly higher than that of the previous patients, and there was no serious adverse reaction. The results showed that NS and TS had the same effect on rh GH, and there was no significant difference in each point of follow up, but compared with GHD patients with age / gender matching, the effect of GHD was more significant than that of GHD patients with rh GH.
【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R596
本文编号：2388042
[Abstract]:Noonan syndrome (Noonan syndrome,NS) is an autosomal dominant hereditary disease characterized by short stature, special face and congenital heart disease. Previous studies have shown that recombinant human growth hormone (Recombinant human growth hormone,rh GH) can significantly improve lifetime height in NS patients. However, there are no reports on the clinical characteristics of NS patients and the response to rh GH therapy in China. This study summarized and analyzed the clinical features of 6 patients with NS and the therapeutic effect of rh GH. From May 2009 to August 2015, a series of physical examination, laboratory examination and gene screening were performed on 6 suspected NS patients in the Department of Endocrinology, Peking Union Hospital. Rh GH, was given at 0.10-0.15IU/kg*d dose and followed by regular follow-up. At the same time, 10 patients with Turner's syndrome (Turner Sydrome,TS) and 10 patients with complete growth hormone deficiency (Growth Hormone Deficiency) were compared with age / gender matched patients with rh GH. Six patients had typical facial appearance of NS and could be diagnosed as dwarfism, and 5 patients with congenital heart disease, 5 patients with congenital heart disease. There were 4 cases of abnormal development of bone system and different degrees of bone age backwardness. 6 patients were diagnosed as NS, by gene test, including 4 cases of PTPN11 mutation, 1 case of KRAS mutation, 1 case of SOS1 mutation and 5 cases after rh GH treatment. The annual growth rate was 0 months (3.92 卤1.23) cm/y;, respectively. 3 months (8.36 卤2.57) cm/y; 6 months (8.30 卤1.97) cm/y; 9 months (9.33 卤4.46) cm/y; 12 months (8.80 卤1.20) cm/y. Except for the 9th month, the growth rate was significantly increased at 6 and 12 months after treatment (P0.01). During the 1 year follow-up period, except for one patient entering 3-10th, the other 4 patients were still below 3thth in height. The growth rate of 10 TS patients matched with the age of NS was higher than that of NS patients before treatment and at the 3rd and 6th month after treatment. The growth rate of NS was higher than that of TS patients before treatment and at the 9th and 12th month after treatment. But there was no significant difference (P0.05). Among the 10 patients with TS, 1 case was between 3~10th and 9 cases were 3th.After one year of rh GH treatment, 3 cases were at 3thth, and 7 cases were 3thth. The growth rate of 10 GHD patients matched with the age / sex of NS was significantly higher than that of NS, at the 3rd and 6th month after treatment (P0.05). The growth rate of GHD was higher than that of NS, before and 9 months after treatment, but the growth rate of NS was higher than that of GHD, at 12 months after treatment (P0.05). Before treatment, 1 case was located at 1010 th and 8 cases were 3 ths.After one year of rh GH treatment, 3 cases were located in 3th to 3thth, and the remaining 7 cases remained unchanged in percentile. Adverse events: in 6 cases of TS and 10 cases of GHD, 2 cases, 4 cases and 2 cases of GHD showed subclinical hypothyroidism during follow-up period, and immediately corrected thyroid function with 25ug/d. There were no adverse reactions associated with rh GH during follow-up, such as injection site pain, rash, joint pain and elevated blood glucose. In this study, 6 patients with NS had different degrees of abnormal signs. The annual growth rate of both NS,TS and GHD patients was significantly higher than that of the previous patients, and there was no serious adverse reaction. The results showed that NS and TS had the same effect on rh GH, and there was no significant difference in each point of follow up, but compared with GHD patients with age / gender matching, the effect of GHD was more significant than that of GHD patients with rh GH.
【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R596
【参考文献】
相关硕士学位论文 前1条
1 于萍;68例矮小症患者的基因变异检测和病因研究[D];北京协和医学院;2015年
，本文编号：2388042
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