Hamad Asma, Sherlaw-Sturrock Charlotte A, Glover Kate, Salmon Rachel, Low Karen, Nair Ramya, Sansbury Francis H, Rawlins LettieE, Carmichael Jenny, Horton Rachael, Wedderburn Sarah, Edgerley Katherine, Irving Rachel, Callaghan Mary, Mercer Catherine, McGowan Ruth, Robert Leema, Titheradge Hannah, Naik Swati
West Midlands Genetics Services, Birmingham Women and Childrens NHS Foundation Trust, Birmingham. UK.
Clinical Genetics Department, University Hospitals Bristol and Weston NHS Foundation Trust St Michael's Hospital, Bristol, UK.
Eur J Med Genet. 2023 Apr;66(4):104714. doi: 10.1016/j.ejmg.2023.104714. Epub 2023 Jan 29.
Recurrent chromosome 16p13.11 microduplication has been characterised in the literature as a cause of developmental delay, learning difficulties and behavioural abnormalities. It is a neurosusceptibility locus and has incomplete penetrance and variable expression. Other clinical features, such as cardiac abnormalities have also been reported. The duplicated region contains the MYH11 gene, which encodes the protein myosin-11 and is a component of the myosin heavy chain in smooth muscle. Recent literature has suggested 16p13.11 microduplication as one of the possible risk factors for thoracic aortic aneurysms and dissection (TAAD). Therefore, we studied the detailed phenotype of cases of chromosome 16p13.11 microduplication from seven centres in the United Kingdom (UK) to expand the phenotype, focusing on the cardiac abnormalities.
All individuals with a chromosome 16p13.11 microduplication seen in Clinical Genetics prior to June 2017 in 6 centres (prior to 2018 in the seventh centre) were identified through the regional genetics laboratory databases. A Microsoft Excel® proforma was created and clinical data was collected retrospectively from clinical genetics databases from the seven genetics services in the UK. The data was collated and analysed collectively.
The majority of the individuals presented with (72%) developmental delay and (62%) behavioural abnormalities, in keeping with the published literature. 27% had some dysmorphic features, 14% had visual impairment and 8% had congenital cardiac abnormalities. Echocardiograms were performed in 50% of patients, and only 3.8% patients had aortic dilatation and no one had aortic dissection. 9.7% of patients were found to have a second genetic/chromosomal diagnosis, especially where there were additional phenotypic features.
16p13.11 microduplication is a neurosusceptibility locus and is associated with variable expression. It may be helpful to refer children with 16p13.11 microduplication for a cardiac review for congenital cardiac abnormalities and also for ophthalmological assessment. Further prospective studies with cardiac assessments are recommended in this cohort of patients to determine whether ongoing aortic surveillance is indicated. Guidelines about the frequency of surveillance are indicated, especially in individuals with normal cardiac findings. We also highlight the importance of considering a second diagnosis if the phenotype is inconsistent with that reported.
文献中已将16号染色体p13.11区域的反复微重复描述为发育迟缓、学习困难和行为异常的一个病因。它是一个神经易感性位点，具有不完全外显率和可变表达。也有报道称存在其他临床特征，如心脏异常。重复区域包含MYH11基因，该基因编码肌球蛋白-11蛋白，是平滑肌中肌球蛋白重链的一个组成部分。最近的文献表明，16p13.11微重复是胸主动脉瘤和夹层（TAAD）的可能危险因素之一。因此，我们研究了来自英国七个中心的16号染色体p13.11微重复病例的详细表型，以扩展表型，重点关注心脏异常。
通过区域遗传学实验室数据库，识别出2017年6月之前（第七个中心为2018年之前）在临床遗传学中发现的所有16号染色体p13.11微重复个体。创建了一个Microsoft Excel®格式模板，并从英国七个遗传学服务机构的临床遗传学数据库中回顾性收集临床数据。对数据进行汇总和集体分析。
大多数个体（72%）存在发育迟缓，（62%）存在行为异常，这与已发表的文献一致。27%有一些畸形特征，14%有视力障碍，8%有先天性心脏异常。50%的患者进行了超声心动图检查，只有3.8%的患者有主动脉扩张，没有人有主动脉夹层。9.7%的患者被发现有第二种遗传/染色体诊断，特别是在有其他表型特征的情况下。
16p13.11微重复是一个神经易感性位点，与可变表达相关。对于有16p13.11微重复的儿童，进行心脏检查以排查先天性心脏异常以及进行眼科评估可能会有所帮助。建议对该队列患者进行进一步的前瞻性心脏评估研究，以确定是否需要持续的主动脉监测。需要制定关于监测频率的指南，特别是对于心脏检查结果正常的个体。我们还强调，如果表型与报道的不一致，考虑第二种诊断的重要性。
