Genetic Manifestations and Phenotype Spectrum in Infants With Feeding Difficulty.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI:10.1002/mgg3.70001

Mingyu Han, Wei Shi, Xiangxiang Chen, Dingwen Wu, Yi Sun, Weiyan Wang, Canyang Zhan, Lingling Hu, Tianming Yuan

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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喂养困难婴儿的遗传表现和表型谱。

背景：喂养困难经常与罕见遗传病引起的多系统疾病并发。本研究旨在描述喂养困难婴儿的遗传表现和表型谱：本病例系列包括2018年10月至2022年5月浙江大学医学院附属儿童医院新生儿科收治的6个月以下喂养困难婴儿。所有婴儿均在住院期间接受了全外显子组测序（WES），并对其临床表型和遗传结果进行了分析：在研究的28名婴儿中，9名为早产儿，19名为足月儿。入院年龄中位数为13.5天（IQR为6.5-35），住院时间中位数为16天（IQR为10.5-30）。共有 12 例（42.9%）并发多种畸形。在这些婴儿中，肌张力异常（53.6%）和神经系统问题（42.9%）明显多见。96.2%的病例存在头颅磁共振异常。根据 WES 结果和临床表型的综合分析，共有 22 例（78.3%）患者通过 WES 发现了与疾病相关的基因变异；其中 15 例（53.6%）患者获得了基因诊断，7 例（25%）患者为疑似诊断。与早产儿（55.6%）相比，足月儿（89.5%）的阳性结果更常见。最终，24 名（85.7%）患者存活出院，其中 75% 需要在出院后进行管饲。出院后，五名患者出现了与基因变异有关的新症状，两名患者死亡：结论：喂养困难可能是罕见遗传病表型谱的一个方面。全基因组测序可提高喂养困难婴儿的分子诊断准确性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.