Hansen-Kiss Emily, Beinkampen Sarah, Adler Brent, Frazier Thomas, Prior Thomas, Erdman Steven, Eng Charis, Herman Gail
Center for Molecular and Human Genetics, Nationwide Children's Hospital, Westerville, Ohio, USA.
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
J Med Genet. 2017 Jul;54(7):471-478. doi: 10.1136/jmedgenet-2016-104484. Epub 2017 May 19.
It is recognised that 5% - 10 % of children with macrocephaly and autism spectrum disorder (ASD) and/or intellectual disability (ID) have a heterozygous pathogenic mutation in the tumour suppressor gene that is associated with PTEN hamartoma tumour syndrome. However, the clinical features and course in children with a pathogenic mutation are unclear and have not been well documented.
We undertook a retrospective chart review of children (< 18 years) with pathogenic mutations to ascertain clinical findings, clinical course and possible outcomes.
Clinical and molecular data were collected and analysed for 47 patients with mutation from 38 eligible families. Macrocephaly (average head circumference of + 5.7 SD) with developmental delay, ID and/or ASD were the most common presenting signs/symptoms (66 %). Clinical features included dermatological findings (66 %), gastrointestinal (GI) symptoms (34 %), ASD diagnosis (50 %), abnormal brain imaging (53 % of those examined) and abnormal thyroid imaging (26 %).
This is the largest survey of clinical features in children with pathogenic mutations to date. It confirms earlier reports of increased rates of neurodevelopmental disorders. Dermatological, GI and thyroid abnormalities are age dependent and may not be present at the time of diagnosis, requiring regular monitoring and medical surveillance. Early paediatric diagnosis is important for institution of medical and developmental surveillance as well as for testing other at- risk family members.
人们认识到，患有巨头畸形和自闭症谱系障碍（ASD）及/或智力残疾（ID）的儿童中，有5% - 10%在与PTEN错构瘤肿瘤综合征相关的肿瘤抑制基因中存在杂合性致病突变。然而，具有致病突变的儿童的临床特征和病程尚不清楚，也未得到充分记录。
我们对患有致病突变的儿童（<18岁）进行了回顾性病历审查，以确定临床发现、临床病程和可能的结局。
收集并分析了来自38个符合条件家庭的47例有突变患者的临床和分子数据。巨头畸形（平均头围+5.7标准差）伴发育迟缓、ID和/或ASD是最常见的体征/症状（66%）。临床特征包括皮肤病学表现（66%）、胃肠道（GI）症状（34%）、ASD诊断（50%）、脑部影像学异常（接受检查者中的53%）和甲状腺影像学异常（26%）。
这是迄今为止对具有致病突变儿童临床特征的最大规模调查。它证实了早期关于神经发育障碍发生率增加的报道。皮肤病学、胃肠道和甲状腺异常与年龄有关，可能在诊断时不存在，需要定期监测和医学随访。早期儿科诊断对于开展医学和发育监测以及检测其他高危家庭成员很重要。
