Wang Jiaping, Zhang Qingping, Bao Xinhua, Chen Yan, Yu Shujie
Peking University First Hospital, Beijing 100034, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018 Aug 10;35(4):484-488. doi: 10.3760/cma.j.issn.1003-9406.2018.04.005.
To delineate the clinical and genetic characteristics of patients with Allan-Herndon-Dudley syndrome (AHDS).
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.
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 tachycardia. All patients had abnormal thyroid hormone levels with elevated free triiodothyronine (FT), decreased free tetraiodothyronine(FT), 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 to 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 to T, p.Q306X) was discovered in the two brothers, for which their mother was heterozygous.
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 FT and low FT accompanied by normal TSH. Delayed meylination of white matter is common. It is an X-linked mental retardation caused by SLC16A2 gene mutations.
明确艾伦-赫恩登-达德利综合征（AHDS）患者的临床和遗传特征。
对117例智力残疾和发育迟缓患者进行二代测序基因检测。收集了那些携带SLC16A2基因突变患者的临床表现、脑磁共振成像（MRI）、甲状腺激素水平和心电图等临床信息。
鉴定出5例携带SLC16A2基因突变的男性患者，包括2例患病兄弟和3例散发病例。患者年龄从8个月至8岁不等。所有患者均有严重智力残疾和发育迟缓，包括头部控制差、无法独立坐立、无语言能力以及对外界刺激反应差。所有患者均有肌张力减退、肌张力障碍和锥体束征阳性。3例患者有窦性心动过速。所有患者甲状腺激素水平均异常，游离三碘甲状腺原氨酸（FT）升高、游离甲状腺素（FT）降低，促甲状腺激素（TSH）正常。3例患者的脑MRI显示髓鞘形成延迟。在3例散发病例中，2例分别携带新发突变，即c.61G>T（p.E21X）和c.695_699delATGGT（p.N232SfsX7），1例携带c.42delC（p.W15GfsX69）突变，该突变遗传自其杂合子母亲。在两兄弟中发现了一个无义突变（c.916C>T，p.Q306X），其母亲为该突变的杂合子。
AHDS的特征为严重的精神运动发育迟缓以及先天性肌张力减退、肌张力障碍和锥体束征阳性。患病男性可能出现独特的甲状腺激素异常，包括FT升高和FT降低，同时TSH正常。白质髓鞘形成延迟很常见。它是一种由SLC16A2基因突变引起的X连锁智力障碍。
