The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections
The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections
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DOI：
10.1101/mcs.a002469
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发表时间：
2018-06-01
影响因子：
1.8
通讯作者：
Kingsmore, Stephen F.
中科院分区：
文献类型：
--
作者：
Sweeney, Nathaly M.;Nahas, Shareef A.;Kingsmore, Stephen F.
先天性膈疝（CDH）是由于膈形成不完全导致腹部器官突出进入胸腔而引起的。CDH与肺发育不全、先天性心脏病和肺动脉高压有关。从遗传学上讲，它与非整倍体、染色体拷贝数变异和单基因突变有关。CDH是最昂贵的非心脏先天性缺陷。管理经常需要实施体外膜氧合（ECMO），这增加了管理支出2.4-3.5倍。鼎晖投资的管理费用估计每年超过2.5亿美元。尽管住院存活率为80%-90%，但目前的管理并不完善，因为存活的儿童中有很大一部分存在长期的功能缺陷。我们报告一例早产儿在产前被诊断为CDH和先天性心脏病，他在重症监护室经历了漫长而复杂的过程，接受了多种手术干预，包括心脏手术后ECMO，胃造口管置入Nissen底折叠，气管造口术治疗呼吸衰竭，复发性感染和发育迟缓。快速全基因组测序（rWGS）在ARID1B中发现了一个可能致病的c.3096_3100deICAAAG （p.Lys1033Argfs*32）突变，为Coffin-Sins综合征提供了诊断。她的父母选择了姑息治疗，她当天晚些时候去世了。
Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is assodated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_3100deICAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Sins syndrome. Her parents elected palliative care and she died later that day.