Duyzend Michael, Sud Malika, D'Gama Alissa M, Poorvu Tabitha, Estroff Judy, Wojcik Monica H
Maternal Fetal Care Center, Boston Children's Hospital, Boston, Massachusetts, USA.
Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Prenat Diagn. 2024 Dec 5. doi: 10.1002/pd.6710.
Prenatal genetic diagnosis can impact care across the perinatal continuum; however, prenatal suspicion for genetic disorders may be complicated by incomplete knowledge of fetal rare-disease phenotypes. Here, we describe the prenatal presentations of a cohort of infants with rare genetic conditions who were diagnosed postnatally in a neonatal intensive care unit (NICU), to characterize prenatal presenting features and evaluate why the diagnosis was not identified prenatally.
Retrospective cohort study of infants born over a 7 year period (2017-2023) who were admitted to a Level IV NICU and received a postnatal genetic diagnosis prior to 1 year of age. We identified which of these infants had been imaged prenatally at our Maternal Fetal Care Center (MFCC) as an opportunity for prenatal genetic diagnosis. Clinical data were abstracted from the medical records.
51 cases met the inclusion criteria. Nine of the 51 infants were not strongly suspected to have a genetic syndrome prenatally when seen at the MFCC, as evidenced by lack of prenatal genetic consultation and lack of documented suspicion for a genetic etiology. These cases largely had absent or uncertain prenatal phenotypes. In most cases (42/51, 82.4%), prenatal diagnostic testing was not pursued even if offered. Overall, postnatal diagnoses, of which there was one dual diagnosis, were made by karyotype/FISH (11/52, 21.1%), microarray (8/52, 15.4%), gene panel/targeted testing (17/52, 32.7%), or exome sequencing (16/52, 30.8%).
Our data illustrate the challenges in fetal phenotyping and support a broad approach to prenatal testing to facilitate early genetic diagnosis, which may meaningfully impact postnatal care.
产前基因诊断会影响围产期连续护理；然而，由于对胎儿罕见病表型了解不全面，产前对基因疾病的怀疑可能会变得复杂。在此，我们描述了一组患有罕见基因疾病的婴儿在新生儿重症监护病房（NICU）出生后被诊断出的产前表现，以确定产前呈现的特征，并评估为何产前未确诊。
对在7年期间（2017 - 2023年）出生并入住四级NICU且在1岁前接受产后基因诊断的婴儿进行回顾性队列研究。我们确定了其中哪些婴儿在我们的母胎护理中心（MFCC）进行了产前成像，作为产前基因诊断的机会。临床数据从病历中提取。
51例符合纳入标准。在MFCC就诊时，51例婴儿中有9例在产前未被强烈怀疑患有基因综合征，这表现为缺乏产前基因咨询以及缺乏对基因病因的记录怀疑。这些病例大多产前表型缺失或不确定。在大多数情况下（42/51，82.4%），即使提供了产前诊断检测，也未进行。总体而言，产后诊断（其中有一例双重诊断）通过核型分析/荧光原位杂交（FISH）（11/52，21.1%）、微阵列分析（8/52，15.4%）、基因panel/靶向检测（17/52，32.7%）或外显子组测序（16/52，30.8%）做出。
我们的数据说明了胎儿表型分析中的挑战，并支持采用广泛的产前检测方法以促进早期基因诊断，这可能会对产后护理产生重大影响。
