Objective: To investigate the clinical, pathological and genetic characteristics of neonatal alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV). Methods: The clinical manifestations, radiographic examinations, pathology and parental genetic analysis of a newborn with FOXF1 variation induced ACDMPV, who was hospitalized in the Department of Neonatology of Shenzhen Children's Hospital in January 2020, were extracted and analyzed. Related literature up to March 2020 with the key words of "Alveolar capillaries dysplasia" "Alveolar capillary dysplasia with misalignment of the pulmonary veins" "FOXF1" in PubMed, CNKI, Wanfang, CQVIP database and Leiden Open Variation database (LOVD) were searched. Results: A full-term male newborn （1 hour of age） was admitted due to anal atresia. Surgical repair of anal atresia and omphalocele was performed on the first day of life, and gallbladder absence and Meckel's diverticulum were identified during the operation. Respiratory distress with hypoxemia developed at about 6 hours of life, and persistent pulmonary hypertension developed and progressed after surgery, with poor response to mechanical ventilation and pulmonary vasodilators. This infant passed away at 26 days of life. Lung biopsy showed decreased alveolar units and thickened interalveolar septa, reduced alveolar capillary density and thickened walls of peripheral pulmonary arteries, and misaligned pulmonary veins adjacent to the pulmonary arterioles, which were consistent with ACDMPV. The whole exome sequencing revealed a heterozygous novel frameshift of FOXF1 gene located in chromosome 16q24.1 c376_377insT; p.(Pro126fs). According to the bioinformatics analysis, this variation was likely to be pathogenic as it was associated with coding disorder of FOXF1 Pro126, resulting in truncation of the encoded protein. This novel variation had not been reported in the human gene mutation database (HGMD), ESP6500siv2_ALL, 1000g2015aug_ALL or dbSNP147 database. Previous 6 literatures reported 54 variants, including 28 missense, 10 nonsense, 11 frameshift, 2 deletion, 1 synonymous, and 2 extensions. Only three of the reported 45 cases （24 males, 21 females） were still alive as of the time of this study. Conclusions: Typically, ACDMPV is a catastrophic disease in neonatal period with high mortality. Lung biopsy and genetic testing should be considered in infants who present with persistent pulmonary hypertension and refractory hypoxemia, especially when combined with extrapulmonary abnormalities.
目的： 探讨肺泡毛细血管发育不良伴肺静脉错位（ACDMPV）患儿的临床特点、病理表现及基因变异类型。 方法： 回顾性分析2020年1月深圳市儿童医院新生儿科收治的1例ACDMPV新生儿的病例资料，分析其临床表现、辅助检查、病理结果及家系关系。以“肺泡毛细血管发育不良”“alveolar capillary dysplasia”“alveolar capillary dysplasia with misalignment of the pulmonary veins”“FOXF1”分别作为检索词，检索PubMed、中国知网、万方、维普数据库及莱顿开放变异数据库建库至2020年3月文献，总结该病的诊断思路。 结果： 患儿 男，1小时龄，因“发现肛门闭锁1 h”入院。6小时龄出现呼吸窘迫伴低氧血症。B超提示胆囊缺如。1日龄行肛门闭锁和脐膨出修补术中发现美克尔憩室。患儿术后持续性肺动脉高压加重，常规降肺动脉压力治疗效果欠佳，26日龄死亡。肺活检提示肺泡单位减少，间质增厚；肺泡毛细血管密度下降；肺动脉管壁中层增厚，肺静脉位置异常且附着于肺小动脉，符合ACDMPV。全外显子组测序分析发现位于染色体16q24.1的FOXF1基因杂合移码变异c376_377insT;p.（Pro126fs），未见相关文献报道。预测会导致所编码蛋白质自第126位脯氨酸开始发生编码紊乱，使得所编码的蛋白质发生截短从而丧失其正常功能。人类基因组突变数据库未见文献报道；ESP6500siv2_ALL、千人基因组（1000g2015aug_ALL）和dbSNP147数据库均未见收录。综合考虑，认为该变异为致病性变异。复习文献纳入英文文献6篇共54个变异位点，包括错义变异28个、无义变异10个、移码变异11个、缺失变异2个、同义变异1个、延伸变异2个。资料齐全病例45例(男24例、女21例），文献报道仅有3例仍存活。 结论： ACDMPV尚无有效治疗手段，病死率高。当新生儿出现难治性低氧血症及持续性肺动脉高压，或伴有肺外畸形时，应及时进行肺组织活检及基因学检查。.
Keywords: Genes; Infant, newborn; Pathology; Pulmonary alveoli.