Abstract：
To evaluate genetic testing use in infants with congenital diaphragmatic hernia (CDH) over the past decade to better inform future practices and individualize prognostication and management.
A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children\'s Hospital of Philadelphia, born between January 2011 and February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed.
The charts of 411 infants were analyzed. Overall, 22% (n = 89) were complex/syndromic and 78% (n = 322) were isolated/nonsyndromic. Mortality was significantly higher in complex/syndromic infants (P < .001) and in infants with diagnostic genetic testing (P < .001). Microarray was diagnostic in 9% (n = 34/399) and exome sequencing was diagnostic in 38% (n = 15/39). Genetic testing was diagnostic in 57% (n = 51/89) of complex/syndromic infants, but in only 2% of isolated/nonsyndromic infants (n = 8/322). Overall, genetic testing was diagnostic in 14% (n = 56).
The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/nonsyndromic infants do not have a genetic etiology identified. This finding underscores the need for additional genetic and genomic studies (eg, whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH.
A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children\'s Hospital of Philadelphia, born between January 2011 and February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed.
The charts of 411 infants were analyzed. Overall, 22% (n = 89) were complex/syndromic and 78% (n = 322) were isolated/nonsyndromic. Mortality was significantly higher in complex/syndromic infants (P < .001) and in infants with diagnostic genetic testing (P < .001). Microarray was diagnostic in 9% (n = 34/399) and exome sequencing was diagnostic in 38% (n = 15/39). Genetic testing was diagnostic in 57% (n = 51/89) of complex/syndromic infants, but in only 2% of isolated/nonsyndromic infants (n = 8/322). Overall, genetic testing was diagnostic in 14% (n = 56).
The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/nonsyndromic infants do not have a genetic etiology identified. This finding underscores the need for additional genetic and genomic studies (eg, whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH.
摘要：
评估过去十年中先天性膈疝（CDH）婴儿的基因检测使用情况，以更好地为未来的实践提供信息并个性化预测和管理。
对费城儿童医院肺发育不良计划中所有CDH患儿进行了回顾性队列研究，出生于2011年1月至2021年2月。对于每个婴儿来说，人口统计信息,产前和产后史，和基因检测进行了回顾。
分析了411例婴儿的图表。总的来说,22%（n=89）为复杂/综合征，78%（n=322）为孤立/非综合征。复杂/综合征婴儿（P<.001）和诊断性基因检测婴儿（P<.001）的死亡率明显更高。微阵列诊断为9%(n=34/399),外显子组测序诊断为38%(n=15/39)。基因检测诊断为57％（n=51/89）的复杂/综合征婴儿，但只有2%的孤立/非综合征婴儿(n=8/322)。总的来说,14%(n=56)的患者进行基因检测诊断.
该队列的高诊断率凸显了全面基因检测在CDH婴儿中的实用性。然而,43％的复杂/综合征婴儿和98％的孤立/非综合征婴儿没有确定的遗传病因。这一发现强调了对额外遗传和基因组研究的需求(例如，全基因组,RNA测序）以识别新基因和突变机制（单基因，监管要素，复杂的特征），这将提高诊断率并最终对CDH婴儿进行个性化管理。
对费城儿童医院肺发育不良计划中所有CDH患儿进行了回顾性队列研究，出生于2011年1月至2021年2月。对于每个婴儿来说，人口统计信息,产前和产后史，和基因检测进行了回顾。
分析了411例婴儿的图表。总的来说,22%（n=89）为复杂/综合征，78%（n=322）为孤立/非综合征。复杂/综合征婴儿（P<.001）和诊断性基因检测婴儿（P<.001）的死亡率明显更高。微阵列诊断为9%(n=34/399),外显子组测序诊断为38%(n=15/39)。基因检测诊断为57％（n=51/89）的复杂/综合征婴儿，但只有2%的孤立/非综合征婴儿(n=8/322)。总的来说,14%(n=56)的患者进行基因检测诊断.
该队列的高诊断率凸显了全面基因检测在CDH婴儿中的实用性。然而,43％的复杂/综合征婴儿和98％的孤立/非综合征婴儿没有确定的遗传病因。这一发现强调了对额外遗传和基因组研究的需求(例如，全基因组,RNA测序）以识别新基因和突变机制（单基因，监管要素，复杂的特征），这将提高诊断率并最终对CDH婴儿进行个性化管理。
