五例Allan-Herndon-Dudley综合征患儿的临床及遗传学特点分析  

Clinical and genetic features of five patients with AIlan-Herndon-Dudley syndrome

作　　者：王佳平 章清萍[1] 包新华[1] 陈岩[1] 于淑杰 Wang Jiaping,Zhang Qingping , Bao Xinhua , Chen Yan , Yu Shujie(Peking University First Hospital, Beijing 100034, China ; Department of Neurology, Harbin Children＇s Hospital, Harbin, Heilongjiang 150010, Chin)

机构地区：[1]北京大学第一医院,100034 [2]哈尔滨市儿童医院神经内科,150010

出　　处：《中华医学遗传学杂志》2018年第4期484-488,共5页Chinese Journal of Medical Genetics

摘　　要：目的阐明Allan- H erndon-Dudley综合征（Allan-Herndon-Dudley syndrome, AHDS）的临床及遗传学特征。方法对117例智力低下患儿进行靶向捕获二代测序，对具有SLC16A2基因突变的AHDS患儿的临床资料包括临床表现、头颅影像学、甲状腺激素、心电图等进行总结。结果共发现5例SLC16A2基因突变的AHDS男性患儿，包括1个家系（2例患儿）及3例散发病例。就诊年龄8个月至8岁，5例患儿均表现为严重的智力运动发育落后，不能抬头、不会独坐，无语言，对外界反应迟钝；5例患儿均有躯干部肌张力低下，且均有肌张力不全和锥体束症状，3例患儿有窦性心动过速。5例患儿均存在甲状腺素水平异常，表现为游离三碘甲状腺原氨酸升高，游离四碘甲状腺原氨酸降低，促甲状腺激素正常。3例患儿进行了头颅磁共振检查，均显示髓鞘化落后。3例散发病例中，2例为SLC16A2基因新发突变，分别为C．61G〉T（P．E21X）、C．695_699delATGGT（P．N232SfsX7），1例突变遗传自母亲，为C．42delC（P．W15GfsX69），家系病例两兄弟的突变均为c．916C〉T（P．Q306X），遗传自母亲。结论AHDS以严重智力运动落后为主要表现；以肌张力低下、肌张力不全、锥体束征为主要的神经系统异常体征；甲状腺激素水平紊乱是提示本病的重要线索。中枢神经系统髓鞘化延迟也是AHDS的特征之一。本病属X连锁智力低下，由SLC16A2基因突变所致。Objective To delineate the clinical and genetic characteristics of patients with Allan- Herndon-Dudley syndrome （AHDS）. Methods Genetic testing was carried out by next generation sequencing on 117 patients featuring intellectual disability and developmental delay. Clinical information including clinical manifestation, brain magnetic resonance imaging （MRI）, thyroid hormone levels, and electrocardiogram was collected for those with SLC16A2 mutations, Results Five male patients with SLC16A2 gene mutations were identified, including 2 affected brothers and 3 sporadic cases. The ages of the patients ranged from 8 months to 8 years. All patients presented with severe intellectual disability and developmental delay including poor head control, inability to sit independently, no speech, and poor response to external stimuli. All patients presented with hypotonia, dystonia, and positive pyramidal signs. Three patients had sinus tachyeardia. All patients had abnormal thyroid hormone levels with elevated free triiodothyronine （FT3）, decreased free tetraiodothyronine（FT4 ）, and normal thyroid stimulating hormone （TSH）. Brain MRI on 3 patients showed delayed myelination. Among the 3 sporadic patients, 2 carried de novo mutations including c. 61G〉T（p. E21X） and c. 695_699delATGGT （p. N232SfsX7）, respectively, 1 carried a c. 42delC （p. W15GfsX69）mutation, which was inherited from his heterozygous mother. A nonsense mutation （c. 916C〉T, p. Q306X） was discovered in the two brothers, for which their mother was heterozygous. Conclusion AHDS is characterized by severe psychomotor developmental delay as well as congenital hypotonia, dystonia and positive pyramidal signs. Affected males may present with distinctive thyroid hormone abnormalities including increased FT3 and low FT4 accompanied by normal TSH. Delayed meylination of white matter is common. It is an X-linked mental retardation caused by SLC16A2 gene mutations.

关 键 词：Allan-Herndon-Dudley综合征 甲状腺激素 X连锁智力低下 SLC16A2基因 

分 类 号：R725.9[医药卫生—儿科]