Division of Neonatology, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA; Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA; Roberts Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, PA.
The Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia, Philadelphia, PA.
J Pediatr. 2022 Sep;248:108-113.e2. doi: 10.1016/j.jpeds.2022.04.012. Epub 2022 Apr 14.
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.
评估过去十年中先天性膈疝 (CDH) 婴儿的基因检测使用情况，以便更好地为未来的实践提供信息，并对预后和管理进行个体化。
对 2011 年 1 月至 2021 年 2 月期间在费城儿童医院肺发育不良计划中登记的所有 CDH 婴儿进行了回顾性队列研究。对每个婴儿的人口统计学信息、产前和产后病史以及基因检测进行了回顾。
共分析了 411 名婴儿的图表。总体而言，22%（n=89）为复杂/综合征，78%（n=322）为单纯/非综合征。复杂/综合征婴儿的死亡率明显更高（P<.001），且进行诊断性基因检测的婴儿死亡率更高（P<.001）。微阵列诊断率为 9%（n=34/399），外显子组测序诊断率为 38%（n=15/39）。基因检测在 57%（n=51/89）的复杂/综合征婴儿中具有诊断意义，但在仅 2%的单纯/非综合征婴儿（n=322）中具有诊断意义。总体而言，基因检测的诊断率为 14%（n=56）。
本队列中的高诊断率突显了对 CDH 婴儿进行全面基因检测的效用。然而，43%的复杂/综合征婴儿和 98%的单纯/非综合征婴儿未确定遗传病因。这一发现强调了需要进行额外的遗传和基因组研究（例如，全基因组、RNA 测序），以识别新的基因和突变机制（单基因、调控元件、复杂特征），从而提高诊断率，并最终对 CDH 婴儿进行个体化管理。
