Department of Neonatology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
National Clinical Research Center for Child Health, Hangzhou, China.
Mol Genet Genomic Med. 2024 Aug;12(8):e70001. doi: 10.1002/mgg3.70001.
Feeding difficulties frequently co-occur with multisystem disorders attributed to rare genetic diseases. In this study, we aimed to describe the genetic manifestations and phenotype spectrum in infants experiencing feeding difficulties.
This case series included infants under 6 months old with feeding difficulties admitted to the neonatal department of Children's Hospital, Zhejiang University School of Medicine from October 2018 to May 2022. All infants underwent whole-exome sequencing (WES) during hospitalisation, and their clinical phenotypes and genetic results were analyzed.
Among 28 infants studied, nine were preterm and 19 were full-term. Median admission age was 13.5 days (IQR 6.5, 35), with a median hospital stay of 16 days (IQR 10.5, 30). Overall, 12 (42.9%) cases were complicated with multiple malformations. Abnormal muscle tone (53.6%) and neurological issues (42.9%) were notable prevalent in these infants. Cranial MR abnormalities were noted in 96.2% of cases. Based on the combined analysis of WES results and clinical phenotypes, a total of 22 (78.3%) patients displayed disease-related genetic variation identified through WES; among them, 15 (53.6%) patients received genetic diagnoses, while 7 (25%) patients were suspected diagnoses. Positive findings were more frequent in full-term (89.5%) than preterm infants (55.6%). Ultimately, 24 (85.7%) patients were discharged alive, with 75% requiring post-discharge tube feeding. Following discharge, five patients developed new symptoms linked to genetic variants, and two patients died.
Feeding difficulty may constitute a facet of the phenotypic spectrum of rare genetic diseases. Whole-exome sequencing can enhance molecular diagnosis accuracy for infants with feeding difficulties.
喂养困难常与罕见遗传疾病引起的多系统疾病同时发生。本研究旨在描述有喂养困难的婴儿的遗传表现和表型谱。
本病例系列纳入 2018 年 10 月至 2022 年 5 月在浙江大学医学院附属儿童医院新生儿科住院的有喂养困难的 6 月龄以下婴儿。所有婴儿在住院期间均进行全外显子组测序（WES），并分析其临床表型和遗传结果。
28 例婴儿中，9 例为早产儿，19 例为足月儿。中位入院年龄为 13.5 天（IQR，6.5，35），中位住院时间为 16 天（IQR，10.5，30）。总体而言，12 例（42.9%）患儿伴有多种畸形。这些婴儿中明显存在异常肌张力（53.6%）和神经系统问题（42.9%）。96.2%的病例存在头颅磁共振异常。基于 WES 结果和临床表型的综合分析，共有 22 例（78.3%）患者通过 WES 显示与疾病相关的遗传变异；其中，15 例（53.6%）患者获得了基因诊断，7 例（25%）患者疑似诊断。足月儿（89.5%）阳性发现的频率高于早产儿（55.6%）。最终，24 例（85.7%）患者存活出院，75%需要出院后管饲喂养。出院后，5 例患者出现与遗传变异相关的新症状，2 例患者死亡。
喂养困难可能构成罕见遗传疾病表型谱的一个方面。全外显子组测序可以提高有喂养困难婴儿的分子诊断准确性。
