Yang Yung-Yu, Liu Chun-Ting, Pai Li-Fan, Hu Chih-Fen, Chen Shyi-Jou, Hsu Wan-Fu
Department of General Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Front Pediatr. 2022 Feb 28;10:825298. doi: 10.3389/fped.2022.825298. eCollection 2022.
Chromosome 17p13.3 microduplication syndrome is considered a multisystem disorder that results in a wide variety of clinical manifestations including dysmorphic facial characteristics, brain structural malformations, developmental restriction, growth restriction, and neurocognitive disorders. The two major classes of chromosome 17p13.3 microduplication, which have different clinical presentations, are associated with specific genetic regions. Among the various known phenotypes, scattered cases with congenital heart disease (CHD) have been reported for both classes of chromosome 17p13.3 microduplication syndrome. Unfortunately, there is insufficient understanding of the correlation between chromosome anomaly induced alterations in gene expression and aberrant cardiac development, and thus early diagnosis of CHD among patients with chromosome 17p13.3 microduplication is difficult without routine prenatal cardiac assessment. One such congenital heart anomalies known to affect a substantial number of newborns worldwide is ventricular septal defect (VSD), which has been found in 17p13.3 microduplication carriers, and seems to sometimes undergo spontaneous closure. We report an unprecedented case of moderate sized perimembranous-outlet VSD and congestive heart failure (CHF) in a Chinese Han male infant with a class II chromosome 17p13.3 microduplication. Despite the fact that cytogenic testing and fetal echocardiography confirmed a 249-Kb chromosome duplication within 17p13.3 that encompassed the gene and showed the presence of VSD during prenatal period, this patient still developed a range of symptoms including sustained prolonged feeding, dyspnea, diaphoresis and retarded growth. A physical examination indicated hepatomegaly and a grade III/VI pan-systolic murmur along the left upper sternal border. Laboratory testing showed a high serum pro-B-type natriuretic peptide (pro-BNP). Imaging studies revealed cardiomegaly and a persistent VSD with related pulmonary stenosis. Since the clinical findings were compatible with CHF, we provided mainline treatment with digoxin, captopril, and furosemide, as well as fluid restriction. Despite sustained poor weight gain, the feeding behavior and the respiratory conditions of the patient improved gradually. This case report and literature review suggest that patients carrying chromosome 17p13.3 microduplication who have VSD may have an increased risk of developing CHF as young infants and hence a comprehensive cardiac evaluation is warranted to allow the early diagnosis and management of any severe heart anomalies.
17号染色体p13.3微重复综合征被认为是一种多系统疾病，可导致多种临床表现，包括面部畸形特征、脑结构畸形、发育受限、生长受限和神经认知障碍。17号染色体p13.3微重复主要分为两类，临床表现不同，与特定的基因区域相关。在各种已知的表型中，两类17号染色体p13.3微重复综合征均有散发性先天性心脏病（CHD）病例的报道。不幸的是，对于染色体异常引起的基因表达改变与心脏发育异常之间的相关性了解不足，因此，在没有常规产前心脏评估的情况下，很难对17号染色体p13.3微重复患者的CHD进行早期诊断。一种已知在全球范围内影响大量新生儿的先天性心脏异常是室间隔缺损（VSD），在17p13.3微重复携带者中发现了这种情况，而且似乎有时会自发闭合。我们报告了一例前所未有的病例，一名患有II类17号染色体p13.3微重复的中国汉族男婴，患有中等大小的膜周部-流出道室间隔缺损和充血性心力衰竭（CHF）。尽管细胞遗传学检测和胎儿超声心动图证实17p13.3区域内有一个249-Kb的染色体重复，其中包含该基因，并且在孕期显示存在室间隔缺损，但该患者仍出现了一系列症状，包括持续长时间喂养困难、呼吸困难、多汗和生长发育迟缓。体格检查显示肝肿大，左胸骨上缘有III/VI级全收缩期杂音。实验室检查显示血清前B型利钠肽（pro-BNP）升高。影像学研究显示心脏扩大和持续性室间隔缺损伴相关肺动脉狭窄。由于临床症状与CHF相符，我们给予地高辛、卡托普利和呋塞米进行一线治疗，并限制液体摄入。尽管体重持续增加不佳，但患者的喂养行为和呼吸状况逐渐改善。该病例报告和文献综述表明，携带17号染色体p13.3微重复且患有室间隔缺损的患者在婴幼儿期发生CHF的风险可能增加，因此有必要进行全面的心脏评估，以便早期诊断和处理任何严重的心脏异常。
